Related Terms

• Acquired immunodeficiency syndrome, adipose, AIDS, antibody, bacteria, B-cell, B cell, benzene, biological therapy, biopsy, bone marrow transplant, bone marrow, cancerous, CBC, chemotherapy, collagen, complete blood count, computerized tomography, creosote, CT, CT scan, cytokines, Epstein-Barr, gallium, granular, HD, HIV, Hodgkin's disease, Hodgkin's lymphoma, human immunodeficiency virus, immune system, immunity, immunosuppressive, lactate dehydrogenase, LDH, leukocyte, lumbar puncture, lymph nodes, lymph nodules, lymph vessels, lymph, lymphangiogram, lymphocytes, lymphoid tissue, macrophages, magnetic resonance imaging, malignant, MRI, natural killer cell, NHL, NK cell, non-Hodgkin's lymphoma, organochlorines, pathogen, PET, positron emission tomography, proliferate, radiation, Reed-Sternberg cells, spinal tap, spleen, staging, sulfallate, T-cell, thymus, tonsils, vaccine, virus, white blood cells.

Background

• Lymphoma is a term for various, usually malignant, tumors that arise in the lymph nodes or in other lymphoid tissue. Malignant tumors are cancerous, and metastasize (spread), while benign tumors do not metastasize. Lymphoma encompasses more than 40 related types of cancer that develop from lymphocytes (cells of the immune system). Lymphoma occurs when one of these cells undergoes a transformation into a malignant cell and begins to grow abnormally dividing and forming tumors. The distinctions between types of lymphoma are based on the different characteristics of the cancerous cells.

• Lymphoma that is slow-growing is also called low grade or indolent; fast-growing lymphoma is called high-grade or aggressive.

• Major risk factors include age (most common in individuals in their 60s), immune system status (lowered immunity may lead to lymphoma development), and a family history of lymphoma (genetics may play a large role in who develops lymphoma).

• There are over one million people around the world living with lymphoma. It is estimated that approximately 350,000 new cases of lymphoma are diagnosed worldwide annually.

• Leukemia, lymphoma/myeloma, accounts for 8.7% of all cancers diagnosed each year in the United States. Each day approximately 170 Americans are diagnosed with lymphoma.

• The two main types or groups of lymphoma in humans are Hodgkin's disease (or Hodgkin's lymphoma) and the non-Hodgkin's lymphomas (NHLs). They both produce similar symptoms and differentiation between the two is done using microscopic evaluation of the cancer cells. There are five subtypes of Hodgkin's disease and about 30 subtypes of non-Hodgkin's lymphoma.

• Approximately 60,000 Americans are diagnosed with NHLs in the United States annually, and about 7,000 are diagnosed with Hodgkin's disease. Hodgkin's disease accounts for only one percent of all cancers in the United States, while NHLs represent four percent of all cancers.

• Survival rates for Hodgkin's lymphoma are 83% at five years, 74% at ten years, and 66% at 15 years. For non-Hodgkin's, the rates of survival are 53% at five years, 43% at ten years, and 37% at 15 years. These numbers depend upon the individual.

• The prognosis for lymphomas also depends largely on the type of lymphoma and the grade of lymphoma with which the individual has been diagnosed.

Lymphatic System

• The lymphatic system is an organization of lymph nodes, lymph vessels, and lymph nodules along with lymphoid tissue (including the thymus, spleen, tonsils, and bone marrow) through which lymph circulates and is filtered. Lymph is the clear, colorless fluid that circulates through the lymphatic system. Lymph nodes are small, rounded masses of lymphoid tissue contained in connective tissue (including bone, cartilage, adipose or fat, and collagen). Lymph nodes are found along lymphatic vessels with clusters in certain areas, such as the neck, groin, and armpits.

• The lymphatic system performs several functions in the body. It drains fluid back into the bloodstream from the tissues, filters lymph, filters the blood, and fights infections. As the blood circulates, fluid leaks out into the body tissues. This fluid is important because it carries food to the cells and waste products back to the bloodstream. The leaked fluid drains into the lymph vessels. It is carried through the lymph vessels to the base of the neck where it is emptied back into the bloodstream. This circulation of fluid through the body goes on all of the time. The lymph nodes filter the lymph as it passes through. White blood cells attack any bacteria or viruses they find in the lymph as it flows through the lymph nodes. If cancer cells break away from a tumor, they often become lodged or "stuck" in the nearest lymph nodes. This is the reason doctors check the lymph nodes first when they are working out how far a cancer has grown or spread.

• The spleen is a lymphatic organ that filters the blood removing all of the old worn out red blood cells and destroying them. They are replaced by new red blood cells that have been made in the bone marrow. The spleen also filters out bacteria, viruses, and other foreign particles found in the blood. White blood cells in the spleen attack bacteria and viruses as they pass through. The lymphatic system helps fight infection in many ways, such as helping to make white blood cells (lymphocytes) that produce antibodies. Antibodies are the part of the immune system that attacks specific foreign particles, such as viruses and bacteria, in the body. Macrophages, immune cells found inside the lymph nodes, engulf (swallow up) and destroy foreign particles.

• A lymphocyte is a type of white blood cell involved in the immune system. There are two categories of lymphocytes, namely the large granular (composed of large particles) lymphocytes and the small lymphocytes. The large granular lymphocytes are more commonly known as the natural killer cells (NK cells). The small lymphocytes are the T-cells and B-cells. B-cells produce antibodies. T-cells, when activated, can kill pathogens (disease causing agents) directly. T-cells also play a part in controlling the immune system, preventing the system from inappropriate overactivity or underactivity. After encountering a pathogen (such as a virus or bacteria), B and T cells "remember" the foreign material and are prepared to fight it off if it returns. This is called cellular immunity.

• Cancer can develop in the lymph nodes in two ways. It can either start there as a primary cancer, or it can spread into the lymph nodes from a primary cancer elsewhere in the body. If cancer spreads into the lymph nodes from another part of the body, this is known as secondary or metastatic cancer. Cancer that starts in the lymph nodes is called lymphoma.

• In lymphomas, malignant (cancerous) lymph cells proliferate (multiply), causing lymph node enlargement. Other cancers, such as breast, colon, liver, prostate, and stomach, often invade lymphatic vessels, which can carry cells from the tumor to lymph nodes, where they are trapped and grow into secondary tumors. When other cancers metastasize (spread), lymph nodes are usually involved. Lymph nodes are therefore removed in cancer surgery to detect or prevent tumor spread.

Types of Lymphoma

• Hodgkin's disease or Hodgkin's lymphoma:

• Hodgkin's disease was named after the doctor who first recognized it in 1832, Thomas Hodgkin. If diagnosed early, 75-95% of individuals may be cured.

• Hodgkin's disease is characterized by the growth of Reed-Sternberg cells in the cancer. Reed-Sternberg cells are distinctive giant cells found in individuals with Hodgkin's lymphoma. They can also be found in reactive lymphadenopathy (such as infectious mononucleosis, carbamazepine associated lymphadenopathy) and rarely non-Hodgkin lymphomas. Men typically have higher incidences of Hodgkin's disease (HD) than women. HD is more common in Caucasians than in African Americans, Latinos, or Asians. HD affects both adults and children, although it is most common in two age groups: young adults (in their late teens) and older adults (ages 60 and older). The age differences are more apparent in women, and may be related to the changes in hormones that take place during puberty and menopause. Only about 10-15% of HD cases occur in children who are younger than 16 years of age.

• Non-Hodgkin's lymphoma:

• Nearly 90% of NHLs are B-cell lymphomas. There are 14 types of B-cell lymphomas. The other types of non-Hodgkin lymphomas are T-cell and natural killer (NK) cell lymphomas and immunodeficiency-associated lymphoproliferative disorders (caused by viruses such as Epstein-Barr and human immunodeficiency virus or HIV).

• Diffuse large B-cell lymphoma, a fast-growing lymphoma, and follicular lymphoma, a slow-growing lymphoma, are the two most common B-cell lymphomas. Together, these two types make up more than half of all non-Hodgkin lymphomas.

• B-cell neoplasms (tumors) are divided into two groups, including precursor and mature B-cell neoplasms. An example of a precursor B-cell neoplasm includes precursor B-lymphoblastic leukemia/lymphoma. Mature B-cell neoplasms include B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma, B-cell prolymphocytic leukemia, lymphoplasmacytic lymphoma, splenic marginal zone B-cell lymphoma, nodal marginal zone lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type, hairy cell leukemia, plasma cell myeloma/plasmacytoma, follicular lymphoma, mantle cell lymphoma, diffuse large cell B-cell lymphoma, mediastinal large B-cell lymphoma, intravascular large B-cell lymphoma, primary effusion lymphoma, and Burkitt's lymphoma/Burkitt's cell leukemia.

• T-cell and natural killer (NK) cell neoplasms include precursor T-cell neoplasm (tumor) and mature T-cell and NK-cell neoplasms. Precursor T-cell neoplasms include t-lymphoblastic lymphoma/leukemia and blastic NK lymphoma. Mature T-cell and NK-cell neoplasms include T-cell prolymphocytic leukemia, T-cell granular lymphocytic leukemia, aggressive NK-cell leukemia, adult T-cell lymphoma/leukemia (HTLV1+), extranodal NK/T-cell lymphoma (nasal type), enteropathy-type T-cell lymphoma, hepatosplenic gamma-delta T-cell lymphoma, subcutaneous panniculitis-like T-cell lymphoma, mycosis fungoides/Sézary's syndrome, primary cutaneous anaplastic large cell lymphoma, T/null cell, peripheral T-cell lymphoma (unspecified), angioimmunoblastic T-cell lymphoma, and primary systemic anaplastic large cell lymphoma, T/null cell.

• Sometimes NHLs are described by their location in the body, including central nervous system (CNS, brain and spinal cord) lymphoma, lymphoma of bone, eyelid lymphoma, digestive tract lymphoma, and ocular (eye) lymphoma.

• NHLs are the most common cancer of the lymphatic system and the fifth most common cancer in the United States. The incidence of NHLs has grown by 80% since the early 1970's.

• The majority of NHLs (95%) occur in adults 40-70 years of age. However, some NHL subtypes are among the most common cancers in children. More men than women develop NHLs and rates are particularly high among men who live in locations with a high rate of human immunodeficiency virus (HIV) infection, such as the San Francisco/Oakland area. Individuals with HIV have impaired immune systems, and may be more susceptible to diseases such as cancer (lymphoma and others). NHLs are more common in Caucasians than in Latino, African Americans, and Asians.

Risk Factors and Causes

• The exact causes of lymphoma are not known. Several factors have been linked to an increased risk of developing lymphoma, including non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD), but it is unclear what role they play in the actual development of lymphoma. These factors are discussed below.

• Age: NHLs may occur at any age, but the risk increases with age. The majority of NHLs (95%) occur in adults 40-70 years of age. However, some NHL subtypes are among the most common cancers in children, such as Burkitt's lymphoma. Hodgkin's disease (HD) usually occurs in people in their late teens or in their 60s and older. HD in the elderly is associated with a poorer prognosis than that observed in younger patients.

• Infection: A number of infections by bacteria and viruses appear to increase the risk of both NHLs and HD. Individuals infected with the human immunodeficiency virus (HIV) and those having acquired immunodeficiency syndrome (AIDS), in which the immune system is progressively weakened, are at high risk for developing lymphomas. Infection with certain parasites (such as Plasmodium species) that causes malaria (found in tropical climates) or the Epstein-Barr virus (linked with mononucleosis and chronic fatigue syndrome) appears to raise the risk of a particular type of NHL called Burkitt's lymphoma. An infection with the bacterium Helicobacter pylori, which is known to cause stomach conditions such as ulcers, can cause an immune system response that raises the risk of lymphomas in the digestive system. Infection with human T-lymphocytic virus type 1 (HTLV-1), hepatitis B, or hepatitis C can also increase the chances of developing lymphomas.

• Immunosuppressive therapies: Individuals taking immunosuppressive drug therapies including steroids, such as prednisone (Deltasone®), cyclosporine (Sandimmune®), methotrexate (Rheumatrex®), or azathioprine (Imuran®), may be at an increased risk for developing HD or NHLs. Immunosuppressive drugs are usually taken for conditions such as cancer, rheumatoid arthritis, and organ transplants. These drugs may alter normal immune system function and lower immunity.

• Heredity: Researchers believe that activation of certain abnormal genes may be involved in the development of all cancers, including lymphomas. Evidence suggests that having a family member, such as a parent or sibling (brother or sister) may increase the chances of developing lymphomas.

• Chemical exposure: Certain chemicals found in pesticide products such as lawn and garden chemicals, may increase the risk of developing lymphoma. Recent clinical studies suggest that the increased risk of pesticide exposure and NHLs may be confined to those with a history of asthma.

• Long-term use of hair products, including permanent hair dyes (especially dark colors) and hair straightening chemicals, doubles an individual's risk of developing lymphoma, particularly among women and persons who used hair dyes before 1980. These dyes contained more carcinogenic (cancer-causing) substances than the dyes used today, due to changes in regulation by the U.S. Food and Drug Administration (FDA).

Signs and Symptoms

• Many individuals (up to 75% in Hodgkin's disease) do not exhibit any signs or symptoms.

• Often, the first sign of lymphoma is a painless swelling in the lymph nodes of the neck, under the arms, or in the groin. The definition of an enlarged lymph node is size larger than one centimeter (0.4 inch) in diameter (pea size). Any node that is larger than one centimeter in diameter should be followed closely by a doctor. High-risk enlarged nodes are those larger than three centimeters (more than an inch) in diameter.

• Lymph nodes or tissues elsewhere in the body may also swell, such as in the spleen and tonsils.

• Symptoms include fever, chills, unexplained weight loss, night sweats, lack of energy, and itching. These symptoms are non-specific, meaning they could be conditions such as influenza or immune system deficiencies. Symptoms caused by these infections usually subside within two weeks, while symptoms associated with lymphomas will continue for months and even years.

Diagnosis

• Because most people with lymphoma experience a variety of symptoms that may be caused by other conditions, cancer of the lymph system may be difficult to diagnose. Imaging studies include computerized tomography (CT), magnetic resonance imaging (MRI), nuclear imaging, and positron emission tomography (PET) scans.

• Medical history: If lymphoma is suspected, the doctor will want to obtain a full medical history to uncover any relevant symptoms or risk factors. Medical history can contain family information, past and current health status, and past and present medications. A complete physical examination will supply other clues about possible infection, health problems, or signs of lymphoma. The physician will pay particular attention to the size, location, tenderness, and consistency (firmness) of swollen lymph nodes, and will examine external lymphatic sites for possible disease.

• Blood tests: Complete blood counts (CBCs) are performed. A CBC evaluates certain components (parts) of blood, including hemoglobin (the oxygen-carrying protein in red blood cells), hematocrit (the proportion of red blood cells to plasma in the blood), white blood cells (which fight infection), and platelets (which help with blood clotting).

• Inflammatory markers (cytokines) or enzymes (lactate dehydrogenase, or LDH) may be elevated. Normal LDH values are between one and three millimoles per liter (mmol/L). High levels of LDH in cases in which non-Hodgkin's lymphoma (NHL) is suspected may indicate a more life-threatening form of the cancer.

• Biopsy: Once the doctor suspects that an individual has Hodgkin's disease (HD) or NHL, a biopsy (removal of a small amount of tissue for examination) of an enlarged lymph node is taken.

• If lymphoma is diagnosed, the doctor may want to sample the bone marrow to determine the extent of disease. The bone marrow is sampled by a technique known as bone marrow aspiration. During this procedure, a thin, hollow needle with a syringe attachment is used to aspirate (suction up) a teaspoon-sized sample of liquid bone marrow from the back of the hip bone. A larger needle is then employed to obtain a bone marrow biopsy ("core" biopsy), which removes roughly a one-sixteenth inch piece of bone marrow from the hip site. The individual is generally awake during the procedure, but local anesthetics (such as lidocaine) and sedatives (such as midazolam or Versed®) may be administered. There is usually no pain involved.

• Imaging studies: Imaging studies such as computed tomography (CT or CAT scan) or magnetic resonance imaging (MRI scan) can be performed to look at the size, shape, and location of lymphoma. CT scan is a computer-assisted x-ray that produces cross-sectional images of the body. Magnetic resonance imaging (MRI scan) is a technique that uses electromagnets and radio waves to create computer-generated pictures of the internal organs. CTs and MRIs are particularly useful for detecting enlarged lymph nodes or lymphoma-related abnormalities of the spleen or other organs.

• Nuclear imaging scans can also be used. A gallium scan uses the radioactive chemical gallium attached to the patient's own white blood cells. First, blood is withdrawn from the patient and sent to a nuclear pharmacy while the patient waits. The nuclear pharmacist attaches gallium to the patient's white blood cells in a test tube, and then the mixture is injected back into the patient's body. The body is then scanned with a camera from different angles to see if the gallium (attached to white blood cells) has gathered in a lymph node tumor. The small amounts of gallium used are not harmful.

• The doctor may also use a lymphangiogram, or a form of x-ray in which pictures are made of the lymphatic system. The patient is injected with a special dye that helps to highlight the lymph nodes and their vessels.

• Positron-emission tomographic (PET) scan may be used. PET scan is a newer alternative to lymphangiogram and gallium scans for detecting areas in the body that are affected by lymphoma. A small amount of a radioactive substance is injected into the body and then traced on the PET scan camera. Sites of radioactivity on the scan indicate areas of increased metabolic activity, which implies a tumor.

• Lumbar puncture: Lumbar puncture, or spinal tap, is a procedure in which a thin needle is inserted through the lumbar (lower) backbone, below the level of the spinal cord. Cerebrospinal fluid (CSF) is withdrawn through the needle, and is then analyzed for the presence of lymphoma cells. This test is performed to see whether lymphoma has spread to the central nervous system. The procedure may be painful and requires the use of topical anesthetics such as lidocaine.

• Staging and grading: Once the doctor has diagnosed lymphoma, studies to establish the patient's stage, or how far the cancer has spread, will be performed. Staging lymphoma classifies it according to size, where the cancer is, and whether and how much the cancer has spread around the body or metastasized. Determining a cancer's stage is very important because it tells the doctor which treatment is most likely to work and what the chances of remission or cure (prognosis) are.

• Lymphomas are often described as being "bulky" or "nonbulky." Nonbulky means the tumor is small, while bulky means the tumor is large. Nonbulky disease has a better prognosis than bulky disease.

• Grade is also an important component of the lymphoma classification and includes low-, intermediate-, and high-grade lymphoma. Low grade lymphomas grow slowly, but low-grade lymphomas are often widespread when discovered. Because they grow slowly, they usually do not require immediate treatment unless organ function is compromised. Symptoms of low-grade lymphomas include peripheral adenopathy (swelling of the lymph nodes) that is painless and slowly progressive. It is the most common clinical symptom seen in individuals with low-grade lymphoma. Splenomegaly, or enlargement of the spleen, is also seen in approximately 40% of individuals with low-grade lymphoma. B symptoms, including temperature over 100 degrees Fahrenheit, night sweats, and weight loss greater than 10% from original weight within six months, are not common initially, but are common in individuals with advanced or end-stage disease.

• Intermediate grade lymphomas are rapidly growing (aggressive) lymphomas that usually require immediate treatment, but they are often curable. High grade lymphomas are very rapidly growing and aggressive lymphomas that require immediate, intensive treatment and are much less often curable. Most individuals with both intermediate- and high-grade lymphomas have adenopathy (also called lymphadenopathy, or lymph node swelling), with more than one third of individuals having lymph node involvement and swelling in the gastrointestinal (GI) tract, skin, bone marrow, sinuses, genitourinary (GU) tract, thyroid, and central nervous system (CNS).

Complications

• Early complications of lymphoma include enlarged lymph nodes, sometimes causing other symptoms by pressing against a vein or lymphatic vessel (swelling of an arm or leg), a nerve (pain, numbness, or tingling), or the stomach (early feeling of fullness). Enlargement of the spleen may cause abdominal pain or discomfort.

• As the disease progresses, metastasis (spread) to other organs can result in organ damage. This can result in death. However, lymphomas are treatable if found early.

Treatment

• The most important factor in the treatment of lymphoma is the stage and grade of the disease. The number and regions of lymph nodes affected and whether only one or both sides of the diaphragm are involved are important considerations. Other factors affecting decisions about treating this disease include age (the older the individual, the more complications may occur with aggressive treatments), the symptoms, pregnancy, and the individual's overall health status.

• The goal of treatment is to improve quality of life and increase prognosis.

• Standard first-line therapy (primary therapy) for lymphoma includes radiation therapy for most early-stage lymphomas, or a combination of chemotherapy and radiation. For later-stage lymphomas, chemotherapy is primarily used with radiation therapy added for control of bulky (large tumor) disease. Biological therapy, or immunotherapy, is increasingly being used in addition to or as an alternative to these standard therapies.

• Radiation therapy: Radiation therapy uses high-energy rays to kill cancer cells. It is considered a local therapy, meaning that it should be used to target areas of the body with tumor masses. A radiation oncologist will plan and supervise therapy. The area to be treated will be carefully mapped out and the treatment machine will be adjusted so that only the lymphoma cells are exposed to a full dose of radiotherapy. Because of the need to target the radiation at exactly the right area of the body, a mould is sometimes made that will help to hold that part of the body still and in position during the treatment sessions.

• Normal cells surrounding the lymphoma are spared the full dose, and these cells are usually able to repair themselves more easily than lymphoma cells. Therefore, radiotherapy can often control or destroy lymphoma cells, while causing only temporary damage to normal cells.

• Radiotherapy is usually given on an outpatient basis, with the patient visiting the hospital up to five times a week. Before each treatment, the patient is carefully positioned, usually lying on a treatment table. Parts of the body that are not being treated may be covered. It is important to remain completely still during the treatment. Each treatment usually lasts only a few minutes and causes no discomfort. Although the patient is left alone during the actual treatment, the radiotherapy technicians watch from an observation room and it is possible to talk to them through a microphone. A course of radiotherapy typically lasts for between two and six weeks, depending on the patient's individual circumstances. The length of radiation treatment varies depending on the stage of the disease. Radiation therapy may be used alone, but is commonly used in conjunction with chemotherapy.

• Depending on how and where the radiation is administered, it may cause certain side effects such as fatigue (extreme tiredness), loss of appetite, nausea, diarrhea, and skin problems. Radiation of lymph node areas may result in suppression of the immune system to varying degrees. Irradiation of the underlying bone and the marrow within the bone may result in suppression of the blood counts.

• Chemotherapy: When the disease progresses and involves more lymph nodes or other organs, chemotherapy is the preferred treatment. Chemotherapy uses specific drugs in combination to kill tumor cells. A major concern with chemotherapy is the possibility of long-term side effects and complications, such as heart damage, lung damage, liver damage, and secondary cancers (including leukemia). Although these severe effects occur in only a small number of people, great effort is being put into finding equally effective regimens with less toxicity. Drug regimens have been developed that substantially diminish the likelihood of long-range, life-threatening complications, including acute leukemia in people who have received multiple courses of chemotherapy and radiation therapy.

• Chemotherapy regimens for lymphoma are commonly referred to by their initials, including ABVD, which consists of doxorubicin (Adriamycin®), bleomycin (blenoxane® or Myleran®), vinblastine (Velban® or Velsar®), and dacarbazine (DTIC-Dome®). BEACOPP consists of bleomycin (blenoxane® or Myleran®), etoposide (Vepesid®), doxorubicin (Adriamycin®), cyclophosphamide (Cytoxan®), vincristine (Oncovin®), procarbazine (Matulane®), and prednisone (Deltasone®). COPP/ABVD consists of cyclophosphamide (Cytoxan®), vincristine (Oncovin®), procarbazine (Matulane®), prednisone (Deltasone®), doxorubicin (Adriamycin®), bleomycin (blenoxane® or Myleran®), vinblastine (Velban® or Velsar®), and dacarbazine (DTIC-Dome®). Stanford V consists of doxorubicin (Adriamycin®), vinblastine (Velban® or Velsar®), mechlorethamine (Mustargen®), etoposide (Vepesid®), vincristine (Oncovin®), bleomycin (blenoxane® or Myleran®), and prednisone (Deltasone®). MOPP consists of mechlorethamine (Mustargen®), vincristine (Oncovin®), procarbazine (Matulane®), and prednisone (Deltasone®). MOPP was once the basic treatment for lymphoma, but it is very toxic. ABVD therapy produces less severe side effects, and is currently the preferred treatment.

• Chemotherapy side effects: Side effects of chemotherapy include nausea, vomiting, enteritis (inflammation of the intestine), diarrhea, musositis (mouth irritation and inflammation), neutropenia (low white blood cell count), and alopecia (hair loss). Medications used for side effects include the anti-nausea drugs ondansetron (Zofran®) and prochlorperazine (Compazine®).

• Bone marrow transplant: If the disease recurs after an initial chemotherapy-induced remission, high-dose chemotherapy and transplantation of the patient's own (autologous) bone marrow or peripheral stem cells may lead to prolonged remission. Peripheral stem cells are bone marrow cells mobilized from the bone marrow into the bloodstream. Because high doses of chemotherapy destroy bone marrow, the patient's own marrow or peripheral blood stem cells are collected before treatment and frozen. The patient will undergo chemotherapy, and then their own bone marrow cells, which have been protected from the effects of the treatment, are injected back into the body. The hospitalization period is from four to six weeks, during which time the patient is isolated and under strict monitoring because of a weakened immune system and an increased risk of infection. The patient will require attentive follow-up care for two to three months after discharge from the hospital. After infusion, it can take 10-20 days for the bone marrow to establish itself. Then they can help produce cells of the immune system (B-cells) to help fight infection. This is a surgical procedure performed under general anesthesia.

• Biological therapy: Biological therapies are sometimes referred to as immunotherapy. Immunotherapy increases the body's natural immunity to help fight off cancer and other pathogens (disease-causing agents). These non-standard therapies are attractive because they offer anticancer effects without many of the undesirable side effects of standard therapies. There are many different types of biological therapies. Examples of biological therapies include the use of monoclonal antibodies, cytokines, and vaccines. Biological therapies may cause flu-like side effects such as chills, diarrhea, fever, loss of appetite, muscle aches and weakness, and nausea/vomiting. Biological therapies are administered in the hospital, clinic, or in a doctor's office.

• Monoclonal antibodies: Antibodies are substances produced by lymphocytes to fight pathogens. Every cell, organism, or pathogen within the body carries markers on its surface that antibodies may recognize. These surface markers are called antigens. A monoclonal antibody is an antibody that is made in a laboratory to find and attach itself to a specific antigen. Monoclonal antibodies can be used to help one's own immune systems kill tumor cells and other pathogens directly, or they can deliver cancer-killing therapies (such as radiation or chemotherapy) directly to a specific antigen found on cancer cells.

• Rituximab (Rituxan®) is the only form of stand-alone biologic therapy approved by the U.S. Food and Drug Administration (FDA) for the treatment of B-cell non-Hodgkin's lymphoma. Rituximab is a type of monoclonal antibody that helps the immune system specifically target and destroy cancer cells. Rituximab is frequently used in combination with chemotherapy. It is also sometimes given in tandem with radio-immunotherapy. Other investigational monoclonal antibodies for lymphoma include Ibritumomab tiuxetan (Zevalin®) and tositumomab (Bexxar®).

• Cytokines: These naturally occurring chemicals are produced by the body to stimulate the cells in the immune system and other organs. They can also be produced artificially and administered in large doses to patients with greater effect. Cytokines stimulate the immune system and help increase the individual's immunity. Examples of cytokins include interferons and interleukins.

• Vaccines: Unlike the more familiar vaccines for infectious diseases such as polio and flu, cancer vaccines do not prevent the disease. Rather, they are designed to stimulate the immune system to mount a specific response against the cancer. Vaccines also help the body create a "memory" of the cancer so that the immune system activates very early in cases of recurrence, thus preventing the development of a new tumor.

• Others: Some drugs treat the side effects of chemotherapy. Anemia (low number of red blood cells) is a frequent side effect of chemotherapy and may cause symptoms such as extreme tiredness, dizziness, or shortness of breath. Epoetin alfa (Procrit®, Epogen®) is a synthetic hormone that stimulates red blood cell production and is used for the treatment of chemotherapy-related anemia. Immune system deficiencies caused by chemotherapy may be treated with filgrastim (Neupogen®), a human granulocyte colony-stimulating factor (G-CSF).

Integrative Therapies

• Good scientific evidence:

• Greater celandine: Ukrain™, a semisynthetic drug derived from greater celandine (Chelidonium majus), has been studied in clinical trials of various types of cancer with consistently positive outcomes. However, the quality of the research performed to date is inadequate, and higher quality studies are needed.

• Use cautiously in patients taking amphetamines, morphine, hexobarbital, MAOIs, or dopaminergic or serotonergic drugs, or in patients undergoing radiation therapy. Avoid in patients with liver disease or in pregnant and lactating women.

• Guided imagery: Early research suggests that guided imagery may help reduce cancer pain. Further research is needed to confirm these results.

• Guided imagery is usually intended to supplement medical care, not to replace it, and guided imagery should not be relied on as the sole therapy for a medical problem. Contact a qualified health care provider if mental or physical health is unstable or fragile. Never use guided imagery techniques while driving or doing any other activity that requires strict attention. Use cautiously with physical symptoms that can be brought about by stress, anxiety or emotional upset because imagery may trigger these symptoms. If feeling unusually anxious while practicing guided imagery, or with a history of trauma or abuse, speak with a qualified health care provider before practicing guided imagery.

• Meditation: There is good evidence that various types of meditation may help improve quality of life in cancer patients. Studies have shown benefits for mood, sleep quality, and the stresses of treatment. The specific effects of meditation are not fully understood. Additional research is needed in this area.

• Use cautiously with underlying mental illnesses. People with psychiatric disorders should consult with their primary mental healthcare professional(s) before starting a program of meditation, and should explore how meditation may or may not fit in with their current treatment plan. Avoid with risk of seizures. The practice of meditation should not delay the time to diagnosis or treatment with more proven techniques or therapies, and should not be used as the sole approach to illnesses.

• Psychotherapy: Psychotherapy is an interactive process between a person and a qualified mental health care professional (psychiatrist, psychologist, clinical social worker, licensed counselor, or other trained practitioner). There is good evidence that psychotherapy may enhance quality of life in cancer patients by reducing emotional distress and aiding in coping with the stresses and challenges of cancer. Therapy may be supportive-expressive therapy, cognitive therapy or group therapy. While some patients seek psychotherapy in hopes of extending survival, there conclusive evidence of effects on medical prognosis is currently lacking. Psychotherapy may help people come to terms with the fact that they may die of cancer, which is the 4th stage of dealing with a terminal illness, including denial, anger, bargaining, and acceptance.

• Psychotherapy is not always sufficient to resolve mental or emotional conditions. Psychiatric medication is sometimes needed. The reluctance to seek and use appropriate medication may contribute to worsening of symptoms or increased risk for poor outcomes. In order to be successful, psychotherapy requires considerable personal motivation and investment in the process. This includes consistent attendance and attention to treatment recommendations provided by the practitioner. Not all therapists are sufficiently qualified to work with all problems. The client or patient should seek referrals from trusted sources and should also inquire of the practitioner's training and background before committing to work with a particular therapist. Some forms of psychotherapy evoke strong emotional feelings and expression. This can be disturbing for people with serious mental illness or some medical conditions. Psychotherapy may help with post-partum depression, but is not a substitute for medication, which may be needed in severe cases.

• Yoga: Yoga is an ancient system of relaxation, exercise, and healing with origins in Indian philosophy. Several studies report enhanced quality of life in cancer, lower sleep disturbance, decreased stress symptoms and changes in cancer-related immune cells after patients received relaxation, meditation and gentle yoga therapy. Yoga is not recommended as a sole treatment for cancer but may be helpful as an adjunct therapy.

• Yoga is generally considered to be safe in healthy individuals when practiced appropriately. Avoid some inverted poses with disc disease of the spine, fragile or atherosclerotic neck arteries, risk for blood clots, extremely high or low blood pressure, glaucoma, detachment of the retina, ear problems, severe osteoporosis, or cervical spondylitis. Certain yoga breathing techniques should be avoided in people with heart or lung disease. Use cautiously with a history of psychotic disorders. Yoga techniques are believed to be safe during pregnancy and breastfeeding when practiced under the guidance of expert instruction (the popular Lamaze techniques are based on yogic breathing). However, poses that put pressure on the uterus, such as abdominal twists, should be avoided in pregnancy.

• Unclear or conflicting scientific evidence:

• Acupuncture: Acupuncture, or the use of needles to manipulate the "chi" or body energy, originated in China over 5,000 years ago. There has been limited research on acupuncture for cancer pain, and the research that was done was shown to have mixed results. More studies are needed to determine potential benefits. Evidence from several small studies supports use of acupuncture at a specific point on the wrist (P6) to help chemotherapy patients reduce nausea and vomiting. Acupuncture may also reduce the pain associated with cancer.

• Needles must be sterile in order to avoid disease transmission. Avoid with valvular heart disease, infections, bleeding disorders or with drugs that increase the risk of bleeding (anticoagulants), medical conditions of unknown origin, or neurological disorders. Avoid on areas that have received radiation therapy and during pregnancy. Use cautiously with pulmonary disease (like asthma or emphysema). Use cautiously in elderly or medically compromised patients, diabetics or with history of seizures. Avoid electroacupuncture with arrhythmia (irregular heartbeat) or in patients with pacemakers.

• Aloe: Transparent gel from the pulp of the meaty leaves of Aloe vera has been used on the skin for thousands of years to treat wounds, skin infections, burns, and numerous other skin conditions. Dried latex from the inner lining of the leaf has traditionally been used as an oral laxative. Preliminary research suggests that aloe may help in the area of cancer prevention or may aid in the regression of cancerous tumors. Additional research is needed in this area.

• Caution is advised when taking aloe supplements as numerous adverse effects including a laxative effect, cramping, dehydration and drug interactions are possible. Aloe should not be used if pregnant or breast-feeding, unless otherwise directed by a doctor.

• American pawpaw: Evidence supporting the use of the American pawpaw (Asimina triloba) tree for cancer treatment in humans is largely anecdotal and subjective. However, use in humans has reported minimal side effects, and evidence from animal and test tube studies suggest that American pawpaw extract does have some anticancer activity. Pawpaw standardized extract has been used for 18 months in patients with various forms of cancer. Well-designed studies on the long-term effects of pawpaw extracts are currently lacking. Pawpaw should not be used if pregnant or breast-feeding, unless otherwise directed by a doctor.

• Antineoplastons: Antineoplastons are a group of naturally occurring peptide fractions, which were observed by Stanislaw Burzynski, MD, PhD in the late 1970s to be absent in the urine of cancer patients. There is inconclusive scientific evidence regarding the effectiveness of antineoplastons in the treatment of cancer. Several preliminary human studies (case series, phase I/II trials) have examined antineoplaston types A2, A5, A10, AS2-1, and AS2-5 for a variety of cancer types. It remains unclear if antineoplastons are effective, or what doses may be safe. Until better research is available, no clear conclusion can be drawn.

• Avoid if allergic or hypersensitive to antineoplastons. Use cautiously with high medical or psychiatric risk, an active infection due to a possible decrease in white blood cells, high blood pressure, heart conditions, chronic obstructive pulmonary disease, liver disease or damage, or kidney disease or damage. Avoid if pregnant or breastfeeding.

• Arabinoxylan: Arabinoxylan is made by altering the outer shell of rice bran using enzymes from Hyphomycetes mycelia mushroom extract. Arabinoxylan has been found to improve immune reactions in patients with diabetes and cancer of various types. Arabinoxylan products may contain high calcium and phosphorus levels, which may be harmful for patients with compromised renal (kidney) function. Caution is advised when taking arabinoxylan supplements, as numerous adverse effects including drug interactions are possible. Arabinoxylan should not be used if pregnant or breast-feeding, unless otherwise directed by a doctor.

• Aromatherapy: Healing with fragrant oils has been used for thousands of years. Aromatherapy is often used in people with chronic illnesses (frequently in combination with massage), with the intention to improve quality of life or well-being. There is currently not enough scientific evidence to form a firm conclusion about the effectiveness of aromatherapy for quality of life in cancer.

• Essential oils should only be used on the skin in areas without irritation. Essential oils should be administered in a carrier oil to avoid toxicity. Avoid with a history of allergic dermatitis. Use cautiously if driving or operating heavy machinery. Avoid consuming essential oils. Avoid direct contact of undiluted oils with mucous membranes. Use cautiously if pregnant.

• Art therapy: Art therapy involves the application of a variety of art modalities including drawing, painting, clay and sculpture. Art therapy enables the expression of inner thoughts or feelings when verbalization is difficult or not possible. Limited evidence suggests that art therapy may be of benefit in cancer caregiving for families of cancer patients. Possible benefits include reduced stress, lowered anxiety, increased positive emotions and increased positive communication with cancer patients and health care professionals. Art therapy may also reduce pain and other symptoms in cancer patients. More studies are needed to determine how best to use this form of intervention with this population. Art therapy may also benefit children hospitalized with leukemia during and after painful procedures. Limited available study suggests that art therapy improves cooperation with treatment. Children requested art therapy again when procedures were repeated, and parents reported that children were more manageable after art therapy.

• Art therapy may evoke distressing thoughts or feelings. Use under the guidance of a qualified art therapist or other mental health professional. Some forms of art therapy use potentially harmful materials. Only materials known to be safe should be used. Related clean-up materials (like turpentine or mineral spirits) that release potentially toxic fumes should only be used with good ventilation.

• Astragalus: Astragalus (Astragalus membranaceus) has been used in Chinese medicine for centuries for its immune enhancing properties. Although early laboratory and animal studies report immune stimulation and reduced cancer cell growth associated with the use of astragalus, reliable human evidence in these areas is currently lacking. In Chinese medicine, astragalus-containing herbal mixtures are also sometimes used with the intention to reduce side effects of chemotherapy and other cancer treatments. Astragalus-containing herbal combination formulas may also have beneficial effects in aplastic anemia. Due to a lack of well-designed research, a firm conclusion cannot be drawn.

• Caution is advised when taking astragalus supplements, as numerous adverse effects including drug interactions are possible. Astragalus should not be used if pregnant or breast-feeding, unless otherwise directed by a doctor.

• Baikal skullcap: Although the outcomes of early studies using baikal skullcap for cancer are promising, high-quality clinical studies are needed in this area before a conclusion can be made. Avoid if allergic or hypersensitive to Baikal skullcap (Scutellaria barbata), its constituents, or members of the Lamiaceae family. Use cautiously if taking sedatives and/or operating heavy machinery. Use cautiously if taking antineoplastic (anticancer) agents or agents metabolized by cytochrome P450 enzymes. Avoid if pregnant or breastfeeding. Baikal skullcap is an ingredient in PC-SPES, a product that has been recalled from the U.S. market and should not be used.

• Bee pollen: Bee pollen is considered a highly nutritious food because it contains a balance of vitamins, minerals, proteins, carbohydrates, fats, enzymes, and essential amino acids. Research has found that bee pollen may reduce some adverse effects of cancer treatment side effects. Additional study is needed before a firm recommendation can be made. Caution is advised when taking bee pollen supplements as allergic reactions may occur in sensitive individuals. Bee pollen should not be used if pregnant or breast-feeding, unless otherwise directed by a doctor.

• Beta-glucan: Treatment with a beta-glucan, called lentinan, plus chemotherapy (S-1) may help prolong the lives of patients with cancer that has returned or cannot be operated on. More research is needed in this area. Avoid if allergic or hypersensitive to beta-glucan. When taken by mouth, beta-glucan is generally considered safe. Use cautiously with AIDS or AIDS-related complex (ARC). Avoid using particulate beta-glucan. Avoid if pregnant or breastfeeding.

• Bitter melon: Bitter melon (Momordica charantia) is used in Avurvedic medicine from India to lower blood sugar levels. Research has also found that bitter melon extracts may be beneficial in cancer therapies. MAP30, a protein isolated from bitter melon extract, is reported to possess anti-cancer effects in laboratory studies. Potential anti-cancer effects have not been studied appropriately in humans. Caution is advised when taking bitter melon supplements, as numerous adverse effects including blood sugar lowering and drug interactions are possible. Bitter melon should not be used if pregnant or breast-feeding, unless otherwise directed by a doctor.

• Black tea: Black tea (Camellia sinensis) is from the same plant as green tea, but the leaves are processed differently. Black tea usually contains more caffeine than green tea. Several studies have explored a possible association between regular consumption of black tea and rates of cancer in several populations. This research has yielded conflicting results, with some studies suggesting benefits, and others reporting no effects. Laboratory and animal studies report that components of tea, such as polyphenols, have antioxidant properties and effects against tumors. However, effects in humans remain unclear, and these components may be more common in green tea rather than in black tea. Some animal and laboratory research suggests that components of black tea may actually be carcinogenic, or cancer causing, although effects in humans are not clear. Overall, the relationship of black tea consumption and human cancer prevention remains undetermined.

• Avoid if allergic or hypersensitive to caffeine or tannins. Skin rash and hives have been reported with caffeine ingestion. Use caution with diabetes. Use cautiously if pregnant. Heavy caffeine intake during pregnancy may increase the risk of SIDS (sudden infant death syndrome). Very high doses of caffeine have been linked with birth defects. Caffeine is transferred into breast milk. Caffeine ingestion by infants can lead to sleep disturbances/insomnia. Infants nursing from mothers consuming greater than 500 milligrams of caffeine daily have been reported to experience tremors and heart rhythm abnormalities. Tea consumption by infants has been linked to anemia, decreased iron metabolism, and irritability.

• Bovine cartilage: In early study, bovine tracheal cartilage (preparations such as Catrix® and VitaCarte®) has been studied for the treatment of cancer with encouraging results. High quality clinical research is needed to better determine the effectiveness of bovine tracheal cartilage preparations for cancer treatment.

• Avoid if allergic or hypersensitive to bovine cartilage or any of its constituents. Use cautiously with cancer, renal (kidney) failure, or hepatic (liver) failure. Avoid if pregnant or breastfeeding.

• Bromelain: Bromelain is a sulfur-containing digestive enzyme (proteins which help with digestion) that is extracted from the stem and the fruit of the pineapple plant (Ananas comosus). There is not enough information to recommend for or against the use of bromelain in the treatment of cancer, either alone or in addition to other therapies. One small study found that a bromelain supplement decreased tumor size in 12 breast cancer patients. Patients took the supplements for different periods of time, lasting from months to years. Caution is advised when taking bromelain supplements, as numerous adverse effects including blood thinning and drug interactions are possible. Bromelain should not be used if pregnant or breast-feeding, unless otherwise directed by a doctor.

• Cat's claw: Originally found in Peru, the use of cat's claw (Uncaria tomentosa) has been said to date back to the Inca civilization, possibly as far back as 2,000 years. Cat's claw has anti-inflammatory properties, and several low-quality studies suggest that cat's claw may slow tumor growth. However, this research is early and has not identified specific types of cancer that may benefit; thus, the results are not clear. A few studies suggest that cat's claw may also boost the immune system. Caution is advised when taking cat's claw supplements, as numerous adverse effects including blood thinning and drug interactions are possible. Cat's claw should not be used if pregnant or breast-feeding, unless otherwise directed by a doctor.

• Chaparral: Chaparral was used by the Native Americans for various health conditions. The chaparral component nordihydroguaiaretic acid (NDGA) has been evaluated as a treatment for cancer but due to risk of toxicity is considered unsafe and not recommended for use. Chaparral and NDGA have been associated with cases of kidney and liver failure, liver cirrhosis, kidney cysts, and kidney cancer in humans. In response to these reports, the U.S. Food and Drug Administration (FDA) removed chaparral from its "generally recognized as safe" (GRAS) list in 1970. Chaparral and NDGA are generally considered unsafe and are not recommended for use.

• Avoid if allergic to chaparral or any of its components, including nordihydroguaiaretic acid. Use cautiously if taking blood thinners (anticoagulants), blood sugar medication, or drugs that are broken down by the liver (like amiodarone, phenobarbital, valproic acid). Stop use two weeks before surgery/dental/diagnostic procedures with bleeding risk, and do not use immediately after these procedures. Use cautiously if driving or operating heavy machinery. Avoid if pregnant or breastfeeding.

• Chlorophyll: Preliminary evidence in suggest that chlorophyll may aid in the reduction of side effects associated with photodynamic therapies, such as those used in management of malignant tumors. Further research is required to support the use of chlorophyll as a laser therapy adjunct for cancer treatment.

• Avoid if allergic or hypersensitive to chlorophyll or any of its metabolites. Use cautiously with photosensitivity, compromised liver function, diabetes or gastrointestinal conditions or obstructions. Use cautiously if taking immunosuppressant agents or antidiabetes agents. Avoid if pregnant or breastfeeding.

• Chrysanthemum: Early study indicates that hua-sheng-ping (includes Chrysanthemum morifolium, Glycyrrhiza uralensis, and Panax notoginseng) may be beneficial for patients with precancerous lesions. However, more research is needed.

• Avoid if allergic or hypersensitive to Chrysanthemum, its constituents, or members of the Asteraceae/Compositae family, such as dandelion, goldenrod, ragweed, sunflower, and daisies. Use cautiously if taking medication for gout, cancer, or HIV. Use cautiously with compromised immune systems or if taking immunomodulators. Avoid with photosensitivity or if taking photosensitizers. Avoid large acute or chronic doses of ingested pyrethrin. Avoid pyrethrin with compromised liver function, epilepsy, or asthma. Avoid ocular exposure to pyrethrin. Avoid if pregnant or breastfeeding.

• Coenzyme Q10: Further research is needed to determine if coenzyme Q10 (CoQ10) may be of benefit for cancer when used with other therapies.

• Allergy associated with Coenzyme Q10 supplements has not been reported, although rash and itching have been reported rarely. Stop use two weeks before surgery/dental/diagnostic procedures with bleeding risk and do not use immediately after these procedures. Use caution with a history of blood clots, diabetes, high blood pressure, heart attack, or stroke, or with anticoagulants (blood thinners) or antiplatelet drugs (like aspirin, warfarin, clopidogrel (like Plavix®), or blood pressure, blood sugar, cholesterol or thyroid drugs. Avoid if pregnant or breastfeeding.

• Copper: Copper is a mineral that occurs naturally in many foods, including vegetables, legumes, nuts, grains and fruits, as well as shellfish, avocado, and beef (organs such as liver). Preliminary research reports that lowering copper levels theoretically may arrest the progression of cancer by inhibiting blood vessel growth (angiogenesis). Copper intake has not been identified as a risk factor for the development or progression of cancer. Copper is potentially unsafe when used orally in higher doses than the RDA. Copper supplements should not be used if pregnant or breast-feeding, unless otherwise directed by a doctor.

• Cranberry: Several laboratory studies have reported positive effects of proanthocyanidins, flavonoid components of cranberry (Vaccinium macrocarpon) and other fruits such as blueberries, grape seed, and pomegranate, on health. Based on early laboratory research, cranberry has been proposed for cancer prevention. Additional study is needed in humans before a conclusion can be made.

• Avoid if allergic to cranberries, blueberries or other plants of the Vaccinium species. Sweetened cranberry juice may effect blood sugar levels. Use cautiously with a history of kidney stones. Avoid more than the amount usually found in foods if pregnant or breastfeeding.

• Dandelion: Limited animal research does not provide a clear assessment of the effects of dandelion on tumor growth. Well-conducted human studies are needed to better determine dandelion's effects on cancer.

• Avoid if allergic to chamomile, feverfew, honey, yarrow, or any related plants such as aster, daisies, sunflower, chrysanthemum, mugwort, ragweed, or ragwort. Use cautiously with diabetes or bleeding disorders, gastroesophageal reflux disease (GERD), kidney or liver diseases, or a history of stroke or electrolyte disorders. Monitor potassium blood levels. Stop use two weeks before surgery/dental/diagnostic procedures with bleeding risk and do not use immediately after these procedures. Avoid if pregnant or breastfeeding.

• Echinacea: There is currently a lack of clear human evidence that echinacea affects any type of cancer. The evidence from a small number of clinical trials evaluating efficacy of echinacea in the treatment of radiation-induced leukopenia (decrease in white blood cells) is equivocal. Studies have used the combination product Esberitox®, which includes extracts of echinacea (Echinacea purpurea and pallida) root, white cedar (Thuja occidentalis) leaf, and wild indigo (Baptisia tinctoria)root. Additional clinical studies are needed to make a conclusion.

• Caution is advised when taking echinacea supplements, as numerous adverse effects including drug interactions are possible. Echinacea should not be used if pregnant or breast-feeding, unless otherwise directed by a doctor.

• Essiac®: Essiac® contains a combination of herbs, including burdock root (Arctium lappa), sheep sorrel (Rumex acetosella), slippery elm inner bark (Ulmus fulva), and Turkish rhubarb (Rheum palmatum). The original formula was developed by the Canadian nurse Rene Caisse (1888-1978) and is thought to be effective in cancer therapies, although currently there is not enough evidence to recommend for or against the use of this herbal mixture as a therapy for any type of cancer. Different brands may contain variable ingredients, and the comparative effectiveness of these formulas is not known. None of the individual herbs used in Essiac® has been tested in rigorous human cancer trials, although some components have anti-tumor activity in laboratory studies. Numerous individual patient testimonials and reports from manufacturers are available on the Internet, although these cannot be considered scientifically viable as evidence. Individuals with cancer are advised not to delay treatment with more proven therapies. Caution is advised when taking Essiac® supplements, as numerous adverse effects including drug interactions are possible. Essiac® should not be used if pregnant or breast-feeding, unless otherwise directed by a doctor.

• Focusing: Focusing (experiential therapy) is a method of psychotherapy that involves being aware of one's feelings surrounding a particular issue and understanding the meaning behind words or images conveyed by those feelings. Early evidence suggests focusing may improve mood and attitude in cancer patients. Firm recommendations cannot be made until well-designed clinical trials are available.

• Side effect reporting is rare, but patients should consult with a qualified healthcare practitioner before making decisions about medical conditions and practices. Individuals with severe emotional difficulties should not abandon proven medical and psychological therapies but rather choose focusing as a possible adjunct.

• Folic acid: Folic acid or folate is a form of a water-soluble B vitamin needed for human health. Preliminary evidence suggests that folate may decrease the risk of several types of cancer. Additional research is needed to make a conclusion. Folic acid supplementation may mask the symptoms of pernicious, aplastic, or normocytic anemias caused by vitamin B12 deficiency and may lead to neurological damage.

• Avoid if allergic or hypersensitive to folate or any folate product ingredients. Use cautiously if receiving coronary stents and with anemia and seizure disorders. It is recommended that pregnant women consume 400 micrograms daily in order to reduce the risk of fetal defects. Folate is likely safe if breastfeeding.

• Gamma linolenic acid (GLA): GLA is an omega-6 essential fatty acid. Some laboratory and human studies indicate that GLA may have anti-tumor activity and may be used as a cancer treatment adjunct. Additional research is needed in this area.

• Caution is advised when taking GLA supplements, as numerous adverse effects including an increased risk of bleeding and drug interactions are possible. GLA should not be used if pregnant or breast-feeding, unless otherwise directed by a doctor.

• Garlic: Preliminary human studies suggest that regular consumption of garlic (Allium sativum) supplements may reduce the risk of developing several types of cancer. Some studies use multi-ingredient products so it is difficult to determine if garlic alone may play a beneficial role in cancer prevention. Further well-designed human clinical trials are needed to conclude whether eating garlic or taking garlic supplements may prevent or treat cancer.

• Caution is advised when taking garlic supplements, as numerous adverse effects including an increased risk of bleeding and drug interactions are possible. Garlic should not be used if pregnant or breast-feeding, unless otherwise directed by a doctor.

• Ginseng: Early studies report that ginseng taken by mouth may be of benefit in cancer prevention, especially if ginseng powder or extract is used. Weak studies suggest that ginseng in combination with other herbs may improve cell activity, immune function, and red and white blood cell counts in patients with aplastic anemia; however, other studies have found decreases in blood cell counts. Early studies suggest that ginseng may decrease radiation therapy side effects and may be used as a chemotherapy adjunct to improve body weight, quality of life, and the immune response. There is currently not enough evidence to recommend the use of Panax ginseng or American ginseng for these indications. Study results are unclear, and more research is needed before a clear conclusion can be reached.

• Caution is advised when taking ginseng supplements, as numerous adverse effects including an increased risk of drug interactions are possible. Ginseng should not be used if pregnant or breast-feeding, unless otherwise directed by a doctor.

• Goji: Polysaccharide constituents, such as alpha- and beta-glucans from a variety of plants, are reported to have immune system enhancing properties. In clinical study, Lycium barbarum polysaccharides (LBP) demonstrated a synergistic effect in various cancer treatments, when administered in conjunction with powerful immune stimulating drugs.

• Use cautiously in patients who are taking blood-thinning medications, such as warfarin. Use cautiously in asthma patients and in patients with sulfite sensitivities. The New York Department of Agriculture has detected the presence of undeclared sulfites, a food additive, in two dried goji berry products from China. Avoid in patients who are allergic to goji, any of its constituents, or to members of the Solanaceae family.

• Grape seed: There is currently little information available on the use of grape seed extract in the treatment of human cancer. Further research is needed before a recommendation can be made.

• Avoid if allergic or hypersensitive to grapes or other grape compounds. Use cautiously with bleeding disorders or if taking blood thinners such as warfarin, aspirin, non-steroidal anti-inflammatory drugs (NSAIDS), or anti-platelet agents. Use cautiously with drugs processed using the liver's cytochrome P450 enzyme system. Use cautiously with blood pressure disorders or if taking ACE inhibitors. Avoid if pregnant or breastfeeding.

• Green tea: Green tea is made from the dried leaves of Camellia sinensis, a perennial evergreen shrub. Green tea has a long history of use in health and longevity, dating back to China approximately 5,000 years ago. Although used for centuries to help prevent diseases, the relationship of green tea consumption and human cancer in general remains inconclusive. Evidence from well-designed clinical trials is needed before a firm conclusion can be made in this area.

• Caution is advised when taking green tea supplements, as numerous adverse effects including an increased risk of drug interactions are possible. Green tea should not be used if pregnant or breast-feeding, unless otherwise directed by a doctor.

• Healing touch: Preliminary data suggests that healing touch (HT) may increase quality of life in cancer. However, due to weaknesses in design and the small number of studies, data are insufficient to make definitive recommendations. Studies with stronger designs are needed. HT should not be regarded as a substitute for established medical treatments. Use cautiously if pregnant or breastfeeding.

• Hoxsey formula: "Hoxsey formula" is a misleading name, because it is not a single formula, but rather is a therapeutic regimen consisting of an oral tonic, topical (on the skin) preparations, and supportive therapy. The tonic is individualized for cancer patients based on general condition, location of cancer, and previous history of treatment. An ingredient that usually remains constant for every patient is potassium iodide. Other ingredients are then added and may include licorice, red clover, burdock, stillingia root, berberis root, pokeroot, cascara, Aromatic USP 14, prickly ash bark, and buckthorn bark. A red paste may be used, which tends to be caustic (irritating), and contains antimony trisulfide, zinc chloride, and bloodroot. A topical yellow powder may be used, and contains arsenic sulfide, talc, sulfur, and a "yellow precipitate." A clear solution may also be administered, and contains trichloroacetic acid.

• Well-designed human studies available evaluating the safety or effectiveness of Hoxsey formula are currently lacking. Caution is advised when taking the Hoxsey formula supplements, as numerous adverse effects including an increased risk of drug interactions are possible. Hoxsey formula should not be used if pregnant or breast-feeding, unless otherwise directed by a doctor.

• Hydrazine sulfate: Hydrazine is an industrial chemical marketed as having the potential to repress weight loss and cachexia (muscle wasting) associated with cancer, and to improve general appetite status. However, in large randomized controlled trials, hydrazine has not been proven effective for improving appetite, reducing weight loss, or improving survival in adults. The National Cancer Institute (NCI) sponsored studies of hydrazine sulfate that claimed efficacy in improving survival for some patients with advanced cancer. Trial results found that hydrazine sulfate did not prolong survival for cancer patients. The U.S. Food and Drug Administration (FDA) has received requests from individual physicians for approval to use hydrazine sulfate on a case-by-case "compassionate use" basis on the chance that patients with no other available effective cancer treatment options might benefit from this therapy. The overall controversy in the use of hydrazine sulfate is ongoing, and relevance to clinical practice is unknown. The use of hydrazine sulfate needs to be evaluated further before any recommendations can be made.

• Hydrazine sulfate may cause cancer. Avoid if allergic or hypersensitive to hydrazine sulfate or any of its constituents. Use cautiously with liver or kidney problems, psychosis, diabetes or seizure disorders. Avoid if pregnant or breastfeeding. Side effects have been reported, including dizziness, nausea, and vomiting.

• Iodine: Iodine is an element (atomic number 53), which is required by humans for the synthesis of thyroid hormones (triiodothyronine/T3 and thyroxine/T4). The potential role of non-radioactive iodine in cancer care remains unknown. Antioxidant and anti-tumor effects have been proposed based on laboratory research. In contrast, some scientists have asserted that tumors may uptake more iodine than normal tissues. It has been suggested that high rates of gastric (stomach) cancer or low rates of breast cancer in coastal Japan may be due to high iodine intake, although this has not been demonstrated scientifically. Povidone-iodine solutions have been used as a part of alternative cancer regimens, such as the Hoxsey formula. Preliminary study has also indicated povidone-iodone solution as a potential rectal washout for rectal cancer. Overall, no clear conclusion can be drawn based on the currently available evidence.

• Reactions can be severe, and deaths have occurred with exposure to iodine. Avoid iodine-based products if allergic or hypersensitive to iodine. Do no use for more than 14 days. Avoid Lugol solution and saturated solution of potassium iodide (SSKI, PIMA) with hyperkalemia (high amounts of potassium in the blood), pulmonary edema (fluid in the lungs), bronchitis, or tuberculosis. Use cautiously when applying to the skin because it may irritate/burn tissues. Use sodium iodide cautiously with kidney failure. Avoid sodium iodide with gastrointestinal obstruction. Iodine is safe in recommended doses for pregnant or breastfeeding women. Avoid povidone-iodine for perianal preparation during delivery or postpartum antisepsis.

• Jiaogulan: Preliminary evidence indicates that gypenosides extracted from Gynostemma pentaphyllum may decrease cancer cell viability, arrest the cell cycle, and induce apoptosis (cell death) in human cancer cells. Immune function in cancer patients has also been studied. Additional study is needed in this area.

• Avoid if allergic or hypersensitive to jiaogulan (Gynostemma pentaphyllum), its constituents, or members of the Cucurbitaceae family. Use cautiously with blood disorders or taking anticoagulants or anti-platelet drugs (blood thinners). Use cautiously with diabetes. Avoid if pregnant or breastfeeding.

• Lavender: Perillyl alcohol (POH), derived from lavender (Lavendula officinalis), may be beneficial in the treatment of some types of cancer. Preliminary small studies in humans, involving the use of POH suggest safety and tolerability, but effectiveness has not been established.

• Avoid if allergic or hypersensitive to lavender. Avoid with a history of seizures, bleeding disorders, eating disorders (anorexia, bulimia), or anemia (low levels of iron). Avoid if pregnant or breastfeeding.

• Lutein: Currently, there is insufficient available evidence to recommend for or against the use of lutein for cancer. Available evidence in humans is conflicting.

• Avoid if allergic or hypersensitive to lutein or zeaxanthin. Use cautiously if at risk for cardiovascular disease or cancer. Avoid if pregnant or breastfeeding.

• Lycopene: High levels of lycopene are found in tomatoes and in tomato-based products. Tomatoes are also sources of other nutrients such as vitamin C, folate, and potassium. Several laboratory and human studies examining tomato-based products and blood lycopene levels suggest that lycopene may be associated with a lower risk of developing cancer and may help stimulate the immune system. However, due to a lack of well-designed human research using lycopene supplements, its effectiveness for cancer prevention remains unclear.

• Avoid if allergic to tomatoes or to lycopene. Due to a lack of conclusive data, avoid if pregnant or breastfeeding.

• Maitake mushroom: Maitake is the Japanese name for the edible mushroom Grifola frondosa. Maitake has been used traditionally both as a food and for medicinal purposes. Early studies in the laboratory as well as in humans suggest that beta-glucan extracts from maitake may increase the body's ability to fight cancer. However, these studies have not been well designed, and better research is needed before the use of maitake for cancer can be recommended.

• Caution is advised when taking maitake supplements, as numerous adverse effects including an increased risk of bleeding and drug interactions are possible. Maitake should not be used if pregnant or breast-feeding, unless otherwise directed by a doctor.

• Meditation: Not enough research has shown meditation to be of benefit in cancer prevention. More studies are needed.

• Use cautiously with underlying mental illnesses. People with psychiatric disorders should consult with their primary mental healthcare professional(s) before starting a program of meditation, and should explore how meditation may or may not fit in with their current treatment plan. Avoid with risk of seizures. The practice of meditation should not delay the time to diagnosis or treatment with more proven techniques or therapies, and should not be used as the sole approach to illnesses.

• Melatonin: There are several early-phase and controlled human trials of melatonin in patients with various advanced stage malignancies. There is currently not enough definitive scientific evidence to discern if melatonin is beneficial as a cancer treatment, whether it increases (or decreases) the effectiveness of other cancer therapies, or if it safely reduces chemotherapy side effects.

• Melatonin is not to be used for extended periods of time. Caution is advised when taking melatonin supplements, as numerous adverse effects including drug interactions are possible. Melatonin is not recommended during pregnancy or breastfeeding unless otherwise advised by a doctor.

• Milk thistle: Milk thistle (Silybum marianum) has been used medicinally in China for over 2,000 years, most commonly for the treatment of liver and gallbladder disorders. There are early reports from laboratory experiments that the components silymarin and silibinin found in milk thistle may reduce the growth of human cancer cells. However, effects have not been shown in high-quality human trials.

• Caution is advised when taking milk thistle supplements, as numerous adverse effects including an increased risk of bleeding and drug interactions are possible. Milk thistle should not be used if pregnant or breast-feeding, unless otherwise directed by a doctor.

• Mistletoe: Mistletoe is one of the most widely used unconventional cancer treatments in Europe. Mistletoe extracts have been studied for a variety of human cancers as well as melanoma and leukemia. However, efficacy has not been conclusively proven for any one condition. In fact, some studies have shown lack of efficacy of certain preparations for a variety of cancers. Larger, well-designed clinical trials are needed.

• Caution is advised when taking mistletoe supplements, as numerous adverse effects including nausea, vomiting, and drug interactions are possible. Mistletoe should not be used if pregnant or breast-feeding, unless otherwise directed by a doctor.

• Moxibustion: Moxibustion is a healing technique employed across the diverse traditions of acupuncture and oriental medicine for over 2,000 years. Moxibustion uses the principle of heat to stimulate circulation and break up congestion or stagnation of blood and chi. Moxibustion is closely related to acupuncture as it is applied to specific acupuncture points. Preliminary evidence suggests that moxibustion may reduce side effects of chemotherapy or radiation therapy. More studies are needed.

• Use cautiously over large blood vessels and thin or weak skin. Avoid with aneurysms, any kind of "heat syndrome," cardiac disease, convulsions or cramps, diabetic neuropathy, extreme fatigue and/or anemia, fever, inflammatory conditions, over allergic skin conditions or ulcerated sores, or skin adhesions. Avoid if pregnant or breastfeeding. Avoid areas with an inflamed organ, contraindicated acupuncture points, face, genitals, head, inflamed areas in general, nipples, and skin adhesions. Avoid in patients who have just finished exercising or taking a hot bath or shower. Use cautiously with elderly people with large vessels. It is considered not advisable to bathe or shower for up to 24 hours after a moxibustion treatment.

• Oleander: Laboratory studies of oleander (Nerium oleander) suggest possible anti-cancer effects, although reliable research in humans is not currently available. There are reports that long-term use of oleander may have positive effects in patients several types of cancer. More research is needed.

• Caution is advised when taking oleander supplements, as numerous adverse effects including drug interactions are possible. Oleander should not be used if pregnant or breast-feeding, unless otherwise directed by a doctor.

• Omega-3 fatty acids: Omega-3 fatty acids are essential fatty acids found in some plants and fish. A balance of omega-6 and omega-3 fatty acids is advised for health. Several population studies report that dietary omega-3 fatty acids or fish oil may reduce the risk of developing several different types of cancer. Well conducted clinical trials are necessary before a clear conclusion can be drawn regarding the use of omega-3 fatty acids for cancer prevention.

• Caution is advised when taking omega-3 fatty acid supplements, as numerous adverse effects including an increase in bleeding and drug interactions are possible. Omega-3 fatty acid supplements should not be used if pregnant or breast-feeding, unless otherwise directed by a doctor.

• Para-aminobenzoic acid: N-butyl-p-aminobenzoate (BAB) has been shown to be a lipid-soluble local anesthetic. Early study found significant pain relief in patients with intractable cancer pain after an epidural injection of BAB suspension. Larger scale clinical study is needed to confirm these findings.

• Avoid with known hypersensitivity to PABA or its derivatives. Avoid oral use in children and pregnant or nursing women. Use cautiously in patients with renal disease, bleeding disorders or taking anticoagulants, diabetics or patients at risk for hypoglycemia. Discontinue use if rash, nausea, or anorexia occurs. Pharmaceutical doses of PABA and its derivatives should only be taken under appropriate medical supervision. PABA should not be given concurrently with sulfonamides.

• Perillyl alcohol: Perillyl alcohol has been used to treat cancer. However, high quality scientific studies are lacking. Further research is required before recommendations can be made.

• Avoid if allergic/hypersensitive to perillyl alcohol. Avoid use in the absence of medical supervision. Use cautiously in patients under medical supervision. Avoid if pregnant or breastfeeding.

• Prayer: Initial studies of prayer in patients with cancer (such as leukemia) report variable effects on disease progression or death rates when intercessory prayer is used. Better quality research is necessary before a firm conclusion can be drawn.

• Prayer is not recommended as the sole treatment approach for potentially serious medical conditions, and should not delay the time it takes to consult with a healthcare professional or receive established therapies. Sometimes religious beliefs come into conflict with standard medical approaches, and require an open dialog between patients and caregivers. In clinical study, patients certain that they were receiving intercessory prayer had a higher incidence of complications following cardiac bypass surgery than those who did not know they were being prayed for.

• Reiki: Reiki may contribute to reduced perception of pain, improved quality of life, and reduced fatigue in cancer patients. More studies are needed.

• Reiki is not recommended as the sole treatment approach for potentially serious medical conditions, and should not delay the time it takes to consult with a healthcare professional or receive established therapies. Use cautiously with psychiatric illnesses.

• Reishi mushroom: Reishi (Ganoderma lucidum) has been shown to have antineoplastic and immunomodulatory effects in animal studies. Human studies exist of advanced cancer patients using Ganopoly®, a Ganoderma lucidum polysaccharide extract. Results show improved quality of life and enhanced immune responses, which are typically reduced or damaged in cancer patients receiving chemotherapy and/or radiation therapy. Well-designed long-term studies are needed confirm these results and to determine potential side effects.

• Caution is advised when taking reishi supplements, as numerous adverse effects including an increased risk of bleeding and drug interactions are possible. Reishi should not be used if pregnant or breast-feeding, unless otherwise directed by a doctor.

• Resveratrol: The effects of resveratrol cannot be adequately assessed from trials using foods, wine, or combination products containing resveratrol and other substances. Well-designed clinical trials of resveratrol alone are needed before a recommendation can be made in regards to cancer prevention and/or treatment.

• Avoid if allergic or hypersensitive to resveratrol, grapes, red wine or polyphenols. Resveratrol is generally considered safe and is commonly found in food and beverages. Use cautiously with bleeding disorders, abnormal blood pressure. Use cautiously with drugs that are broken down by the body's cytochrome P450 system or digoxin (or digoxin-like drugs). Avoid if pregnant or breastfeeding.

• Seaweed: Bladderwrack (Fucus vesiculosus) is a brown seaweed that grows on the northern coasts of the Atlantic and Pacific oceans, and the North and Baltic seas. Bladderwrack appears to suppress the growth of various cancer cells in animal and laboratory studies. However, reliable human studies to support a recommendation for use in cancer are currently lacking.

• Caution is advised when taking bladderwrack supplements, as numerous adverse effects including an increased risk of drug interactions are possible. Bladderwrack should not be used if pregnant or breast-feeding, unless otherwise directed by a doctor.

• Selenium: Selenium is a trace mineral found in soil, water, and some foods. It is an essential element in several metabolic pathways. Several studies suggest that low levels of selenium (measured in the blood or in tissues such as toenail clippings), may be a risk factor for developing cancer. Population studies suggest that people with cancer are more likely to have low selenium levels than healthy matched individuals, but in most cases it is not clear if the low selenium levels are a cause or merely a consequence of disease. It currently remains unclear if selenium is beneficial for cancer prevention or cancer treatment.

• Avoid if allergic or sensitive to products containing selenium. Avoid with a history of nonmelanoma skin cancer. Selenium is generally regarded as safe for pregnant or breastfeeding women. However, animal research reports that large doses of selenium may lead to birth defects.

• Shark cartilage: For several decades, shark cartilage has been proposed as a cancer treatment. Studies have shown shark cartilage or the shark cartilage product AE-941 (Neovastat®) to block the growth of new blood vessels, a process called "anti-angiogenesis," which is believed to play a role in controlling growth of some tumors. There have also been several reports of successful treatments of end-stage cancer patients with shark cartilage, but these have not been well-designed and have not included reliable comparisons to accepted treatments. Many studies have been supported by shark cartilage product manufacturers, which may influence the results. In the United States, shark cartilage products cannot claim to cure cancer, and the U.S. Food and Drug Administration (FDA) has sent warning letters to companies not to promote products in this way. Without further evidence from well-designed human trials, it remains unclear if shark cartilage is of any benefit in cancer and patients are advised to check with their doctor and pharmacist before taking shark cartilage.

• Shark cartilage available in Asian grocery stores and restaurants should not be eaten due to declining populations of sharks. Caution is advised when taking shark cartilage supplements, as numerous adverse effects including an increased risk of drug interactions are possible. Shark cartilage should not be used by patients who are pregnant or breast-feeding, unless otherwise directed by a doctor.

• Shiitake mushroom: Shiitake (Lentinus edodes) has been taken by mouth for boosting the immune system, decreasing cholesterol levels, and for anti-aging. Lentinan, derived from shiitake, has been injected as an adjunct treatment for cancer and HIV infection. Laboratory, animal and human studies of lentinan have shown positive results in cancer patients when used as a chemotherapy adjunct. Further well-designed clinical trials on all types of cancer are required to confirm these results.

• Caution is advised when taking shiitake supplements, as numerous adverse effects including an increased risk of bleeding and drug interactions are possible. Shiitake should not be used if pregnant or breast-feeding, unless otherwise directed by a doctor.

• Slippery elm: Slippery elm is found as a common ingredient in a purported herbal anticancer product called Essiac® and a number of Essiac-like products. These products contain other herbs such as rhubarb, sorrel, and burdock root. Currently, there is not enough evidence to recommend for or against the use of this herbal mixture as a therapy for any type of cancer. Avoid if allergic or hypersensitive to slippery elm. Avoid if pregnant or breastfeeding.

• Sorrel: Early evidence suggests that herbal formulations containing sorrel, such as Essiac®, do not shrink tumor size or increase life expectancy in patients with cancer. However, currently there is a lack of studies evaluating sorrel as the sole treatment for cancer. A conclusion cannot be made without further research.

• Avoid with a known allergy or hypersensitivity to sorrel. Avoid large doses due to reports of toxicity and death, possibly because of the oxalate found in sorrel. Many tinctures contain high levels of alcohol and should be avoided when driving or operating heavy machinery. Sorrel formulations may cause nausea or vomiting when taken with the prescription drugs metronidazole (Flagyl®) or disulfiram (Antabuse®). Avoid if pregnant or breastfeeding.

• Soy: Soy (Glycine max) contains compounds which have been reported to be effective as a cancer treatment. Genistein, an isoflavone found in soy, has been found in laboratory and animal studies to possess anti-cancer effects, such as blocking new blood vessel growth (anti-angiogenesis), acting as a tyrosine kinase inhibitor (a mechanism of many new cancer treatments), or causing cancer cell death (apoptosis). In contrast, genistein has also been reported to increase the growth of pancreas tumor cells in laboratory research. Until reliable human research is available, it remains unclear if dietary soy or soy isoflavone supplements are beneficial, harmful, or neutral in people with various types of cancer.

• Caution is advised when taking soy supplements, as numerous adverse effects including an increased risk of drug interactions are possible. Soy should not be used if pregnant or breast-feeding, unless otherwise directed by a doctor.

• Spiritual healing: Cancer patients, especially those who fear recurrence or are unhappy with their physicians, commonly use prayer and spiritual healing. More research is needed to address the effects of spiritual healing on anxiety, depression, and quality of life in patients with cancer.

• Spiritual healing should not be used as the only treatment approach for medical or psychiatric conditions, and should not delay the time it takes to consider more proven therapies.

• Sweet annie: Certain constituents found in sweet annie show promise for use in cancer when used in combination with standard chemotherapy. However, currently there is not enough scientific evidence in humans to make a strong recommendation for this use.

• Avoid if allergic or hypersensitive to sweet annie (Artemisia annua), its constituents, or members of the Asteraceae/Compositae family such dandelion, goldenrod, ragweed, sunflower, and daisies. Use cautiously in patients who are pregnant, taking angiogenic agents, or recovering from surgery or other wounds. Use cautiously if taking cardiotoxic or neurotoxic agents or with compromised cardiac or neural function. Use cautiously if taking immunostimulants or quinolines. Avoid if pregnant or breastfeeding.

• Transcutaneous electrical nerve stimulation (TENS): Transcutaneous electrical nerve stimulation (TENS) is a non-invasive technique in which a low-voltage electrical current is delivered through wires from a small power unit to electrodes located on the skin. Although TENS has been used with some success in cancer pain, there is not enough reliable evidence to draw a firm conclusion in this area. TENS is often used in combination with acupuncture.

• Avoid with implantable devices, like defibrillators, pacemakers, intravenous infusion pumps, or hepatic artery infusion pumps. Use cautiously with decreased sensation, like neuropathy, and with seizure disorders. Avoid if pregnant or breastfeeding.

• Thiamin (Vitamin B1): Thiamin deficiency has been observed in some cancer patients, possibly due to increased metabolic needs. It is not clear if lowered levels of thiamin in such patients may actually be beneficial. Currently, it remains unclear if thiamin supplementation plays a role in the management of any particular type(s) of cancer.

• Thiamin is generally considered safe and relatively nontoxic. Avoid if allergic or hypersensitive to thiamin. Rare hypersensitivity/allergic reactions have occurred with thiamin supplementation. Skin irritation, burning, or itching may rarely occur at injection sites. Large doses may cause drowsiness or muscle relaxation. Use cautiously if pregnant or breastfeeding.

• Thymus extract: Preliminary evidence suggests that thymus extract may increase disease-free survival and immunological improvement in several types of cancer. Additional study is needed in this area.

• Avoid if allergic or hypersensitive to thymus extracts. Use bovine thymus extract supplements cautiously due to potential for exposure to the virus that causes "mad cow disease." Avoid with an organ transplant or other forms of allografts or xenografts. Avoid if receiving immunosuppressive therapy, with thymic tumors, myasthenia gravis (neuromuscular disorder), untreated hypothyroidism, or if taking hormonal therapy. Avoid if pregnant or breastfeeding.

• Traditional Chinese Medicine (TCM): The ancient Chinese philosophy of Taoism provided the basis for the development of Chinese medical theory. TCM uses over 120 different herbs in cancer treatment, depending on the type of cancer and its cause according to Chinese medical theory. Studies have reported significant benefits include reducing tumors, reducing treatment side effects and improved response to treatment. More studies of stronger design are needed before TCM can be recommended with confidence as an adjunct to cancer treatment, although centuries of traditional use in cancer cannot be discounted.

• Chinese herbs can be potent and may interact with other herbs, foods or drugs. Consult a qualified healthcare professional before taking. There have been reports of manufactured or processed Chinese herbal products being tainted with toxins or heavy metal or not containing the listed ingredients. Herbal products should be purchased from reliable sources. Avoid ma huang, which is the active ingredient in ephedra. Avoid ginseng if pregnant or breastfeeding.

• Turmeric: Turmeric (Curcuma longa) is commonly used for its anti-inflammatory properties. Several early animal and laboratory studies report anti-cancer (colon, skin, breast) properties of curcumin. Many mechanisms have been considered, including antioxidant activity, anti-angiogenesis (prevention of new blood vessel growth), and direct effects on cancer cells. Currently it remains unclear if turmeric or curcumin has a role in preventing or treating human cancer. There are several ongoing studies in this area.

• Caution is advised when taking turmeric supplements, as numerous adverse effects including an increased risk of bleeding and drug interactions are possible. Turmeric should not be used if pregnant or breast-feeding, unless otherwise directed by a doctor.

• Vitamin C (ascorbic acid): Dietary intake of fruits and vegetables high in vitamin C has been associated with a reduced risk of various types of cancer in population studies (particularly cancers of the mouth, esophagus, stomach, colon, or lung). However, it is not clear that it is specifically the vitamin C in these foods that is beneficial, and vitamin C supplements have not been found to be associated with this protective effect. Experts have recommended increasing dietary consumption of fruits and vegetables high in vitamin C, such as apples, asparagus, berries, broccoli, cabbage, melon (cantaloupe, honeydew, watermelon), cauliflower, citrus fruits (lemons, oranges), fortified breads/grains/cereal, kale, kiwi, potatoes, spinach, and tomatoes. Vitamin C has a long history of adjunctive use in cancer therapy, and although there have not been any definitive studies using intravenous (or oral) vitamin C, there is evidence that it has benefit in some cases. Better-designed studies are needed to better determine the role of vitamin C in cancer prevention and cancer treatment.

• Avoid if allergic or sensitive to vitamin C product ingredients. Vitamin C is generally considered safe in amounts found in foods. Vitamin C supplements are also generally considered safe in most individuals if taken in recommended doses. Large doses (greater than 2 grams) may cause diarrhea and gastrointestinal upset. Avoid high doses of vitamin C with glucose 6-phosphate dehydrogenase deficiency, kidney disorders or stones, cirrhosis (inflammation of the liver), gout, or paroxysmal nocturnal hemoglobinuria (bleeding disorder). Vitamin C intake from food is generally considered safe if pregnant or breastfeeding. It is not clear if vitamin C supplements in doses higher than Dietary Reference Intake recommendations are safe for pregnant or breastfeeding women. Vitamin C is naturally found in breast milk.

• Vitamin D: Limited research suggests that synthetic vitamin D analogs may play a role in the treatment of human cancers. However, it remains unclear if vitamin D deficiency raises cancer risk, or if an increased intake of vitamin D is protective against some cancers. Until additional trials are conducted, it is premature to advise the use of regular vitamin D supplementation for cancer prevention.

• Avoid if allergic or hypersensitive to vitamin D or any of its components. Vitamin D is generally well-tolerated in recommended doses; doses higher than recommended may cause toxic effects. Use cautiously with hyperparathyroidism (overactive thyroid), kidney disease, sarcoidosis, tuberculosis, and histoplasmosis. Vitamin D is safe in pregnant and breastfeeding women when taken in recommended doses.

• Vitamin E: Reliable scientific evidence that vitamin E is effective as a cancer treatment is currently lacking.

• Caution is merited in people undergoing chemotherapy or radiation, because it has been proposed that the use of high-dose antioxidants may actually reduce the anti-cancer effects of these therapies. This remains an area of controversy and studies have produced variable results. Patients interested in using high-dose antioxidants such as vitamin E during chemotherapy or radiation should discuss this decision with their medical oncologist or radiation oncologist. Caution is advised when taking vitamin E supplements, as numerous adverse effects including an increased risk of bleeding and drug interactions are possible. Avoid if allergic or hypersensitive to vitamin E. Avoid with retinitis pigmentosa (loss of peripheral vision). Use cautiously with bleeding disorders or if taking blood thinners. Avoid above the recommended daily level in pregnant women and breastfeeding women.

• Fair negative scientific evidence:

• Apricot: Available clinical trials on the use of whole apricots for cancer are currently lacking. However, some research has been conducted on "Laetrile™," an alternative cancer drug marketed in Mexico and other countries outside of the U.S. Laetrile™ is derived from amygdalin found in apricot pits and nuts such as bitter almond. There are multiple animal studies and initial human evidence to suggest that Laetrile™ is not beneficial in the treatment of cancer. Based on a phase II trial in 1982, the U.S. National Cancer Institute concluded that Laetrile™ is not an effective chemotherapeutic agent. Nonetheless, many people still travel to use this therapy outside the U.S.

• Multiple cases of cyanide poisoning, including deaths, have been associated with Laetrile™ therapy. Avoid if allergic to apricot, its constituents or members of the Rosaceae family, especially the Prunoideae subfamily of plants. Avoid eating excessive amounts of apricot kernels (about 7 grams daily, or more than ten kernels daily). Use cautiously with diabetes. Use cautiously when taking supplements containing beta-carotene, iron, niacin, potassium, thiamine or vitamin C. Use cautiously when taking products that may lower blood pressure. Avoid if pregnant or breastfeeding.

• Beta-carotene: While diets high in fruits and vegetables rich in beta-carotene have been shown to potentially reduce certain cancer incidences, results from randomized controlled trials with oral supplements do not support this claim.

• There is some concern that beta-carotene metabolites with pharmacological activity can accumulate and potentially have cancer-causing (carcinogenic) effects. A higher, statistically significant incidence of lung cancer in male smokers who took beta-carotene supplements has been discovered. Beta-carotene/vitamin A supplements may have an adverse effect on the incidence of lung cancer and on the risk of death in smokers and asbestos exposed people or in those who ingest significant amounts of alcohol. In addition, high-dose antioxidants theoretically may interfere with the activity of some chemotherapy drugs or radiation therapy. Therefore, individuals undergoing cancer treatment should speak with their oncologist if they are taking or considering the use of high dose antioxidants. Beta-carotene in the amounts normally found in food does not appear to have this adverse effect. Avoid if sensitive to beta-carotene, vitamin A or any other ingredients in beta-carotene products.

• Bitter almond: "Laetrile" is an alternative cancer drug marketed in Mexico and other countries outside of the United States. Laetrile is derived from amygdalin, found in the pits of fruits and nuts such as the bitter almond. Early evidence suggests that laetrile is not beneficial in the treatment of cancer. In 1982, the U.S. National Cancer Institute concluded that laetrile was not effective for cancer therapy. Nonetheless, many people still travel to use this therapy outside the United States.

• Multiple cases of cyanide poisoning, including deaths, have been associated with laetrile therapy. Avoid if allergic to almonds or other nuts. Use cautiously if driving or operating machinery. Avoid if pregnant or breastfeeding because of the risk of birth defects.

• Hypnotherapy, hypnosis: Hypnosis did not reduce radiotherapy side effects such as anxiety and did not improve quality of life in patients undergoing curative radiotherapy in early high-quality studies.

• Use cautiously with mental illnesses like psychosis/schizophrenia, manic depression, multiple personality disorder or dissociative disorders, or with seizure disorders.

• Iridology: There is currently limited available data supporting iridology as a tool for cancer diagnosis. Additional study is needed.

• Iridology should not be used alone to diagnose disease. Studies of iridology have reported incorrect diagnoses, and thus, potentially severe medical problems may go undiagnosed. In addition, research suggests that iridology may lead to inappropriate treatment. Iridology is therefore not recommended as a sole method of diagnosis or treatment for any condition.

• Vitamin E: Recent evidence from well-conducted clinical study reports no reduction in the development of cancer with the use of natural-source vitamin E taken daily. Previously, there have been laboratory, population, and other human trials examining whether vitamin E is beneficial in general cancer prevention, including that for prostate, colon, or stomach cancer. Results of these prior studies have been variable. At this time, based on the best available scientific evidence, and recent concerns about the safety of vitamin E supplementation, vitamin E cannot be recommended for cancer prevention.

• Avoid if allergic or hypersensitive to vitamin E. Avoid with retinitis pigmentosa (loss of peripheral vision). Use cautiously with bleeding disorders or if taking blood thinners. Avoid above the recommended daily level in pregnant women and breastfeeding women.

Author Information

• This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography

Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.

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