Iscador
Eurixor
Isorel
Helixor
Abnoba-viscum

Mistletoe has been evaluated as a treatment for cancer in numerous clinical studies.[1-33] Reviewed in [34-38] One ongoing phase II study in Israel involves carboplatin /gemcitabine in combination with mistletoe as a complementary treatment in patients with non-small cell lung cancer (ECOG-5597 ¹ and NCT00516022 ²). Most studies have been conducted in Europe, primarily in Germany and Austria. However, in 2002, the National Center for Complementary and Alternative Medicine in cooperation with the National Cancer Institute (NCI) began accruing patients to a phase I trial (NCCAM-02-AT-260 ³) of mistletoe (Helixor A) and gemcitabine in patients with advanced solid tumors. The trial is now closed and the data is being analyzed. Another United States trial (NCT00283478 ⁴) of the mistletoe extract Iscar with gemcitabine versus gemcitabine alone as a second-line therapy for non-small cell lung cancer patients who have failed one prior line of chemotherapy is closed.

The mistletoe extracts and products studied in clinical trials were Iscador, Eurixor, Helixor, Lektinol, Isorel, Abnoba-viscum,[39] and recombinant lectin ML-1 (refer to the tables at the end of this section).

Approximately half of the reported studies were controlled studies, and a majority of these were randomized clinical trials. Survival was the principal endpoint measured in most reported studies; however, other endpoints included tumor response, tumor recurrence, and quality of life.

Although mistletoe was found to be therapeutically effective in most of the reported studies, many of the studies had one or more major weaknesses that raised doubts about the reliability of the findings. These weaknesses include registration of small numbers of patients; presence of large numbers of patients who either were not evaluable or were otherwise excluded from the analyses; failure to adequately document mistletoe use, mistletoe dose, and/or interruptions of mistletoe use; absence of control subjects or use of historical control subjects; use of inadequate randomization procedures; absence of treatment blinding; extensive use of subset analysis; and the measurement of mean as opposed to median survival. (Note: In studies with small numbers of patients, the mean survival time, i.e., the average survival time can be greatly exaggerated if one or more patients exhibit unusually long survival; median survival, therefore, is a better measure.) In addition, evaluation of the studies is often hindered by incomplete descriptions of the study design and by incomplete reporting of clinical data, including data about previous and concurrent therapies received by the patients. A selection of studies is discussed below organized by the type of mistletoe extract used.

A three-arm, randomized phase III trial that involved 408 patients with previously untreated, inoperable non-small cell lung cancer was conducted between 1978 and 1987.[21] Patients were randomly assigned to one of the following treatments: (1) subcutaneous injection 3 times a week with IscadorU or IscadorQ (refer to the General Information ⁵ section of this summary for more information); the concentration of mistletoe was increased during a seven-injection sequence or cycle, followed by a 3-day pause, and then the process was repeated; IscadorU was administered for two cycles, followed by two cycles of IscadorQ; both mistletoe preparations contained mercury); (2) intramuscular injection once a week with Polyerga Neu, which is a sheep spleen glycopeptide that is reported to be an immunostimulant and an inhibitor of tumor cell glycolysis; and (3) intramuscular injection once a week with a vitamin B mixture, which served as a placebo. Complete follow-up information was available for 337 patients, and 312 patients (105 Iscador treated, 100 Polyerga Neu treated, and 107 placebo treated) were included in the survival analysis. No statistically significant differences in survival were found between the three groups. Median survival for the Iscador group was 9.1 months; for the Polyerga Neu group, it was 9.0 months; and for the placebo group, it was 7.6 months. The researchers reported that 11.5% of the patients in the Iscador group survived 2 years from the time they entered the trial; the corresponding survival values for the Polyerga Neu and the placebo groups were 13.9% and 10.1%, respectively. In addition, no differences were found between the three groups with respect to tumor response, median body weight, blood chemistry values, Karnofsky Performance Status, and carefully measured quality of life. However, more patients in the Iscador group than in the Polyerga Neu or the placebo groups reported subjective improvement in feelings of well-being (59.4% vs. 43.2% and 44.8%, respectively).

Another randomized phase III trial of mistletoe as a treatment for cancer involved 830 patients with high-risk melanoma (i.e., a primary tumor >3 mm in diameter and no regional lymph nodes positive for cancer or a primary tumor of any size, one or two regional lymph nodes positive for cancer, and no distant metastases) who were randomly assigned to one of the following four groups after potentially curative surgery: (1) treatment with low-dose interferon -alpha, (2) treatment with low-dose interferon-gamma, (3) treatment with IscadorM, or (4) no further treatment. Both types of interferon and IscadorM were administered by subcutaneous injection for a period of 1 year.[24] The interferon injections were administered every other day, whereas IscadorM was administered 3 times a week. After 8 years of follow-up, no increase in survival time or increase in time until melanoma recurrence was demonstrated for mistletoe treatment or treatment with either type of interferon. A nonrandomized, case-control study of long-term mistletoe extract for patients with melanoma, however, showed a survival advantage among patients with high-risk disease.[40]

Three other studies of mistletoe were described in a single published report.[7] The patients in these studies were drawn from 10,226 cancer patients who were participants in a prospective study of the influence of self-regulation (i.e., the ability of a person to achieve a sense of well-being, inner equilibrium, a feeling of competence, and the ability to control stressful situations) on the incidence and course of cancer. Among these individuals, 1,668 patients who had been treated with Iscador, and 8,475 patients who had received no mistletoe therapy were identified.

One of the three studies was a retrospective, prospective matched-pair study of the effectiveness of Iscador as a treatment for cancer.[7] Among the patients who had been treated with Iscador and those who had not, 396 pairs of individuals were identified who were closely matched according to criteria of gender; year of birth within 3 years; year of cancer diagnosis within 3 years; type of cancer; stage of disease; type of metastasis, if present; and type(s) of conventional therapy received. These individuals had rectal cancer, colon cancer, breast cancer, stomach cancer, or lung cancer. It was reported that the mean survival time of the Iscador-treated patients was 39% longer than the mean survival time of the patients who had not been treated with mistletoe (mean survival times = 4.23 years and 3.05 years, respectively). This difference in survival was statistically significant. However, the retrospective nature of this study is a major weakness. Another weakness is the fact that Iscador use was incompletely ascertained. Only the actuality of mistletoe use (yes or no) and its overall duration of use were documented. No information was collected about the type of Iscador used (i.e., the host tree), the dose used, and whether there were any interruptions in use.

The second and third studies were prospective, randomized matched-pair studies (i.e., similar to randomized trials) that involved patients who were drawn from a group of 8,475 individuals who had not been treated with mistletoe.[7] From this group, two sets of matched pairs were created. One set contained 49 pairs of patients who had rectal cancer, colon cancer, stomach cancer, breast cancer, or lung cancer. The other set contained 17 pairs of individuals who had stage II or stage III breast cancer. These studies used the same matching criteria as the retrospective study. In the two sets, one member of each pair was randomly selected as a candidate for mistletoe therapy. These patients were advised to ask their doctor for Iscador treatment. Ultimately, only 39 individuals in the 49-pair set were treated with Iscador and eligible for analysis. All 17 pairs in the second set were eligible for analysis.

The mean survival time of the Iscador-treated patients in the 39-pair set was 42% longer than the mean survival time of the patients who were not treated with mistletoe (mean survival times = 3.49 years and 2.45 years, respectively). The mean survival time of the Iscador-treated patients in the 17-pair set was approximately twice that of the patients who did not receive mistletoe therapy (mean survival times = 4.79 years and 2.41 years, respectively). Both differences in survival were statistically significant.

These two randomized studies, however, had major weaknesses, including the recruitment of small numbers of patients and insufficient documentation of mistletoe use. As in the case of the retrospective study, only the actuality of mistletoe use (yes or no) and the overall duration of mistletoe treatment were ascertained. No information was collected on the type of Iscador used, the dose of Iscador used, and whether there were any interruptions in Iscador therapy.

The use of Iscador as an adjuvant treatment has been examined in several studies. In the following studies, Iscador proved safe and effective and also showed a significant survival advantage over untreated controls.

A retrospective multicenter cohort study of parallel groups examined Iscador as a postoperative adjuvant using safety and efficacy as the main endpoints. A total of 1,442 patient records (710 treated patients and 732 untreated controls) were randomly selected from medical institutions that provided both standard and alternative treatments. Safety and efficacy were measured by the number and severity of adverse drug reactions. The treatment group showed significantly less adverse reactions (confidence interval = 95%; P = < .001) compared with the controls.[41,42]

In a phase l/ll trial of Iscador as an adjuvant postoperative treatment for superficial bladder cancer, mistletoe extract was found to be a safer and more effective alternative to Bacillus Calmette-Guérin (BCG). Thirty patients were administered Iscador instillations 4 weeks after surgery. Patients treated with Iscador did equally well with fewer side effects than a group of historical controls treated with BCG.[43,44]

In another retrospective multicenter cohort study to determine safety and efficacy of Iscador as an adjuvant long-term treatment following surgery for multiple myeloma, 686 patient records were examined (e.g., 357 untreated controls and 329 treated with Iscador). Safety, efficacy, and a cluster of survival endpoints (tumor-related, disease-free, brain-metastases free, and overall survival) were measured. Only mild to intermediate adverse drug reactions were seen in the treated group. Survival analyses showed no evidence of tumor enhancement and increased incidence of brain or other metastases in the Iscador group. Results suggest significant survival benefit for all survival-related endpoints in the treatment group.[40]

Five randomized controlled trials of Eurixor have been published as peer-reviewed articles. The largest of these studies involved 477 patients with squamous cell carcinoma of the head and neck.[4] Reviewed in [37] These patients were randomly assigned to treatment with surgery or surgery and radiation therapy, and they were randomly assigned again to either no additional treatment or treatment with Eurixor. This double randomization produced the following four groups: (1) 105 patients treated with surgery alone; (2) 97 patients treated with surgery and Eurixor; (3) 137 patients treated with surgery and radiation therapy; and (4) 138 patients treated with surgery, radiation therapy, and Eurixor. Eurixor was administered in four treatment cycles over a 60-week period. Each treatment cycle lasted 12 weeks and was followed by a 4-week break period. During each cycle, Eurixor was administered by subcutaneous injection twice a week. Each injection contained enough standardized mistletoe extract to yield a dose of 1 nanogram of ML-1 lectin per kilogram of body weight. The results of this randomized trial showed that treatment with Eurixor did not improve either 5-year disease-free survival or 5-year disease-specific survival. In addition, no stimulation of the immune system or improvement in quality of life was found with Eurixor treatment.

It has been suggested that a less-than-optimum dose of mistletoe was administered to patients in this trial.[7] The same dose of Eurixor, however, has been used in other clinical studies, including studies in which benefit was reported.[1,3,22] In addition, both the dose and the duration of Eurixor treatment in this trial are consistent with those recommended by the manufacturer.[4]

A prospective, randomized phase II trial involved 45 patients who had noninvasive bladder cancer.[5] After surgery, the patients were randomly assigned to receive either three cycles of treatment with Eurixor or no further therapy. The goal of the study was to determine whether Eurixor treatment could reduce bladder cancer recurrence. Twenty-three patients were randomly assigned to the treatment group, and 22 were randomly assigned to the control group. Each cycle of Eurixor treatment consisted of 3 months of subcutaneous injections, administered twice a week, followed by a 3-month break period. One milliliter of Eurixor was administered at each injection. After 18 months of follow-up, 11 recurrences were observed in the treatment group, and eight were observed in the control group. The average time of recurrence for the treatment group was 6.3 months; for the control group, it was 6.4 months. The median disease-free interval for the treatment group was 9 months; for the control group, it was 10.5 months. None of these differences was considered significant.

A major concern about this study, however, is that the dose of lectin ML-1 administered to patients was not adjusted for body weight. If different batches of Eurixor were used for individual patients, the patients may not have received uniform doses throughout the trial. Each milliliter of Eurixor has been reported to contain 50 to 70 nanograms of ML-1. Reviewed in [1,3,35] Therefore, the dose of lectin administered to a person weighing 120 pounds (approximately 55 kg) could have ranged from 0.91 nanograms per kilogram body weight to 1.27 nanograms per kilogram body weight. For a person weighing 160 pounds (approximately 73 kg), the dose of lectin could have ranged from 0.68 nanograms per kilogram body weight to 0.96 nanograms per kilogram body weight. As indicated above, the manufacturer of Eurixor recommends a dose of 1 nanogram per kilogram body weight. Since 33 of the 45 patients in this trial were men and men tend to weigh more than women, it is conceivable that a substantial fraction of the patients were treated with lower-than-recommended doses of ML-1. One other trial that used Eurixor without concurrent therapy involved 16 patients (seven women and nine men) with stage III and IV pancreatic cancer.[6]

Only two trials of Isorel have been reported in the publicly available, online indexed peer-reviewed medical literature. In one study of 64 advanced colorectal cancer patients (Dukes C and D) patients were randomly assigned to three groups: (1) surgery and chemotherapy; (2) surgery and chemotherapy plus Isorel; and (3) surgery alone. Patients receiving treatment with Isorel had a significantly better median survival advantage and a better cumulative survival advantage than patients in the other two groups. In addition there were no side effects to treatment in the Isorel group.[45]

Another study showed that perioperative use of Isorel in the digestive tract of cancer patients resulted in an increase in lymphocytes through 14 days of drug administration. In a group of 70 surgically treated patients, 40 patients were assigned to the Isorel-treated group, and 30 patients were assigned to the control group. The treatment group showed an increase in CD4/CD8 ratio (P = < .05) from the start to end of treatment and an increase in natural killer (NK) cell determinants. NK cell activity and lymphocyte levels declined in the controls. Quality-of-life measures also increased in the treatment group.[46]

In a three-arm randomized trial, patients were randomly assigned to one of the following groups after surgery: Helixor, chemotherapy, or control. Some patients in each group were also treated with local radiation therapy. The number of evaluable patients in the chemotherapy group was 177 with survival in the chemotherapy group superior to that in the control group and equivalent to that in the Helixor group.[19] In another three-arm randomized trial, patients were randomly assigned to receive chemotherapy only (n = 20), chemotherapy plus Helixor (n = 20), or chemotherapy plus Ney-Tumorin (n = 20); Ney-Tumorin is a mixture of peptides and proteins from 15 different organs of fetal and young pigs or cows that is reported to have both antitumor and immunostimulatory properties. The control patients were randomly assigned to chemotherapy only; the treated patients were randomly assigned to receive chemotherapy plus Helixor; and the mean survival time (in months) of patients treated with either Helixor or Ney-Tumorin was approximately twice that of patients treated with chemotherapy only.[17]

No tumor response was seen in any of the 25 patients in a phase ll trial that examined the effect of a mistletoe extract in metastatic colorectal cancer resistant to standard treatment (5- fluorouracil and leucovorin chemotherapy), which used an extract known as Abnoba-viscum. The endpoint of the study was objective tumor response. Patients were administered a gradually increasing daily dose of 0.15 mg to 15 mg. Treatment duration ranged from 4 weeks to 66 weeks. Toxicity levels were mild. Some patients reported relief of disease symptoms.[47]

Refer to the NCI's PDQ Clinical Trials Registry ⁶ for a current list of active clinical trials involving the use of mistletoe in cancer treatment.

References

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Glossary Terms

In medicine, the act of giving a treatment, such as a drug, to a patient. It can also refer to the way it is given, the dose, or how often it is given.

Having to do with stopping abnormal cell growth.

A weakened form of the bacterium Mycobacterium bovis (bacillus Calmette-Guérin) that does not cause disease. Bacillus Calmette-Guérin is used in a solution to stimulate the immune system in the treatment of bladder cancer and as a vaccine to prevent tuberculosis. Also called BCG.

A type of study in which the patients (single-blinded) or the patients and their doctors (double-blinded) do not know which drug or treatment is being given. The opposite of a blinded study is an open label study.

Cancer that forms in tissues of the breast, usually the ducts (tubes that carry milk to the nipple) and lobules (glands that make milk). It occurs in both men and women, although male breast cancer is rare.

Having to do with the bronchi, which are the larger air passages of the lungs, including those that lead from the trachea (windpipe) to the lungs and those within the lungs.

A term for diseases in which abnormal cells divide without control. Cancer cells can invade nearby tissues and can spread to other parts of the body through the blood and lymph systems. There are several main types of cancer. Carcinoma is cancer that begins in the skin or in tissues that line or cover internal organs. Sarcoma is cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system cancers are cancers that begin in the tissues of the brain and spinal cord.

A drug that is used to treat symptoms of ovarian cancer that has come back after treatment with other anticancer drugs or to treat advanced ovarian cancer that has never been treated. It is also used together with other anticancer drugs to treat non-small cell lung cancer and is being studied in the treatment of other types of cancer. Carboplatin is a form of cisplatin that causes fewer side effects in patients. It attaches to DNA (the molecules inside cells that carry genetic information and pass it from one generation to the next) and may cause cancer cells to die. It is a type of platinum compound.

A condition in which cancer is spread widely throughout the body, or, in some cases, to a relatively large region of the body. Also called carcinomatosis.

A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin).

A study that compares two groups of people: those with the disease or condition under study (cases) and a very similar group of people who do not have the disease or condition (controls). Researchers study the medical and lifestyle histories of the people in each group to learn what factors may be associated with the disease or condition. For example, one group may have been exposed to a particular substance that the other was not. Also called retrospective study.

Treatment with drugs that kill cancer cells.

A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease. Also called clinical trial.

Cancer that forms in the tissues of the colon (the longest part of the large intestine). Most colon cancers are adenocarcinomas (cancers that begin in cells that make and release mucus and other fluids).

Cancer that develops in the colon (the longest part of the large intestine) and/or the rectum (the last several inches of the large intestine before the anus).

A treatment that is given at the same time as another.

In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works.

An experiment or clinical trial that includes a comparison (control) group.

A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional treatment.

The length of a straight line that extends from one edge of a tumor or other object, through its center and to the opposite edge. It is usually used to measure the size of round or spherical shapes.

The organs through which food and liquids pass when they are swallowed, digested, and eliminated. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum and anus.

The length of time after treatment for a specific disease during which a patient survives with no sign of the disease. Disease-free survival may be used in a clinical study or trial to help measure how well a new treatment works.

The percentage of people in a study or treatment group who have not died from a specific disease in a defined period of time. The time period usually begins at the time of diagnosis or at the start of treatment and ends at the time of death. Patients who died from causes other than the disease being studied are not counted in this measurement.

The amount of medicine taken, or radiation given, at one time.

Any substance, other than food, that is used to prevent, diagnose, treat or relieve symptoms of a disease or abnormal condition. Also refers to a substance that alters mood or body function, or that can be habit-forming or addictive, especially a narcotic.

Effectiveness. In medicine, the ability of an intervention (for example, a drug or surgery) to produce the desired beneficial effect.

Patients whose response to a treatment can be measured because enough information has been collected.

A drug used in the treatment of cancer. It is a type of antimetabolite. Also called 5-FU.

A drug that is used to treat certain types of breast cancer, pancreatic cancer, ovarian cancer, and lung cancer and is being studied in the treatment of other types of cancer. Gemcitabine is a type of antimetabolite. Also called gemcitabine hydrochloride and Gemzar.

A process in which glucose (sugar) is partially broken down by cells in enzyme reactions that do not need oxygen. Glycolysis is one method that cells use to produce energy. When glycolysis is linked with other enzyme reactions that use oxygen, more complete breakdown of glucose is possible and more energy is produced.

A short chain of amino acids (the building blocks of proteins) that has sugar molecules attached to it. Some glycopeptides have been studied for their ability to stimulate the immune system.

Cancer that arises in the head or neck region (in the nasal cavity, sinuses, lips, mouth, salivary glands, throat, or larynx [voice box]).

An individual treated in the past and used in a comparison group when researchers analyze the results of a clinical study that had no control group. The use of a control, or comparison, group helps researchers determine the effects of a new treatment more accurately.

The complex group of organs and cells that defends the body against infections and other diseases.

A substance that increases the ability of the immune system to fight infection and disease.

Use of a syringe and needle to push fluids or drugs into the body; often called a "shot."

Describes a condition that cannot be treated by surgery.

A biological response modifier (a substance that can improve the body's natural response to infections and other diseases). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and -gamma. The body normally produces these substances. They are also made in the laboratory to treat cancer and other diseases.

Within or into muscle. Also called IM.

A standard way of measuring the ability of cancer patients to perform ordinary tasks. The Karnofsky Performance scores range from 0 to 100. A higher score means the patient is better able to carry out daily activities. KPS may be used to determine a patient's prognosis, to measure changes in a patient’s ability to function, or to decide if a patient could be included in a clinical trial. Also called KPS.

One of a pair of organs in the abdomen. Kidneys remove waste from the blood (as urine), produce erythropoietin (a substance that stimulates red blood cell production), and play a role in blood pressure regulation.

A measure of weight. A kilogram is equal to 2.2 pounds.

A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants.

The active ingredient in a drug used to reduce the toxic effects of folic acid antagonists (substances that block the action of folic acid), especially the anticancer drug methotrexate. It is also used to treat anemia and it is used with fluorouracil to treat symptoms of advanced colorectal cancer. It is also being studied in the treatment of other types of cancer and other conditions. Leucovorin is a form of folic acid, a B-complex vitamin that the body needs to make red blood cells and to function and stay healthy. Leucovorin is a type of chemoprotective agent and a type of chemosensitizing agent. Also called Citrovorum factor and folinic acid.

Cancer that forms in tissues of the lung, usually in the cells lining air passages. The two main types are small cell lung cancer and non-small cell lung cancer. These types are diagnosed based on how the cells look under a microscope.

A type of white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infections and other diseases.

A statistics term. The average value in a set of measurements. The mean is the sum of a set of numbers divided by how many numbers are in the set.

The average time that patients in a clinical study remained alive. The time is measured beginning either at diagnosis or the start of treatment.

A statistics term. The middle value in a set of measurements.

The time from either diagnosis or treatment at which half of the patients with a given disease are found to be, or expected to be, still alive. In a clinical trial, median survival time is one way to measure how effective a treatment is.

A form of cancer that begins in melanocytes (cells that make the pigment melanin). It may begin in a mole (skin melanoma), but can also begin in other pigmented tissues, such as in the eye or in the intestines.

A silver-white, poisonous metal that is a liquid at ordinary temperatures. It is commonly used in thermometers and amalgams, and has been used as an ingredient in some homeopathic medicines and in very small amounts as a preservative in viral vaccines.

The spread of cancer from one part of the body to another. A tumor formed by cells that have spread is called a “metastatic tumor” or a “metastasis.” The metastatic tumor contains cells that are like those in the original (primary) tumor. The plural form of metastasis is metastases (meh-TAS-tuh-SEEZ).

A measure of weight. A milligram is approximately 450,000 times smaller than a pound and 28,000 times smaller than an ounce.

A measure of length in the metric system. A millimeter is one thousandth of a meter. There are 25 millimeters in an inch.

A semiparasitic plant that grows on some types of trees. Mistletoe extracts are being studied as treatments for cancer.

A type of cancer that begins in plasma cells (white blood cells that produce antibodies). Also called Kahler disease, myelomatosis, and plasma cell myeloma.

A measure of weight. One nanogram weighs a billion times less than one gram, and almost a trillion-times less than a pound.

The National Cancer Institute, part of the National Institutes of Health of the United States Department of Health and Human Services, is the Federal Government's principal agency for cancer research. The National Cancer Institute conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the National Cancer Institute Web site at http://www.cancer.gov. Also called NCI.

A federal agency that uses science to explore complementary and alternative medicine (CAM) practices, trains CAM researchers, and provides authoritative information about CAM to professionals and the public. NCCAM awards grants for research projects, training, and career development in CAM; sponsors conferences, educational programs, and exhibits; studies ways to use proven CAM practices along with conventional medical practice; and supports adding CAM to medical, dental, and nursing school programs. NCCAM is part of the National Institutes of Health. Also called NCCAM.

A type of white blood cell that contains granules with enzymes that can kill tumor cells or microbial cells. Also called large granular lymphocyte and NK cell.

A group of lung cancers that are named for the kinds of cells found in the cancer and how the cells look under a microscope. The three main types of non-small cell lung cancer are squamous cell carcinoma, large cell carcinoma, and adenocarcinoma. Non-small cell lung cancer is the most common kind of lung cancer.

A clinical study that includes some, but not all, of the eligible patients identified by the researchers during the study registration period. This type of study does not usually have a control group.

A clinical trial in which the participants are not assigned by chance to different treatment groups. Participants may choose which group they want to be in, or they may be assigned to the groups by the researchers.

Describes a condition that can be treated by surgery.

A glandular organ located in the abdomen. It makes pancreatic juices, which contain enzymes that aid in digestion, and it produces several hormones, including insulin. The pancreas is surrounded by the stomach, intestines, and other organs.

A molecule that contains two or more amino acids (the molecules that join together to form proteins). Peptides that contain many amino acids are called polypeptides or proteins.

Around the time of surgery. This usually lasts from the time the patient goes into the hospital or doctor's office for surgery until the time the patient goes home.

A trial to study the safety, dosage levels, and response to a new treatment.

A study to test whether a new treatment has an anticancer effect (for example, whether it shrinks a tumor or improves blood test results) and whether it works against a certain type of cancer.

A study to compare the results of people taking a new treatment with the results of people taking the standard treatment (for example, which group has better survival rates or fewer side effects). In most cases, studies move into phase III only after a treatment seems to work in phases I and II. Phase III trials may include hundreds of people.

An inactive substance or treatment that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.

The main result that is measured at the end of a study to see if a given treatment worked (e.g., the number of deaths or the difference in survival between the treatment group and the control group). What the primary endpoint will be is decided before the study begins.

The original tumor.

In medicine, a study or clinical trial in which participants are identified and then followed forward in time.

A molecule made up of amino acids that are needed for the body to function properly. Proteins are the basis of body structures such as skin and hair and of substances such as enzymes, cytokines, and antibodies.

The overall enjoyment of life. Many clinical trials assess the effects of cancer and its treatment on the quality of life. These studies measure aspects of an individual’s sense of well-being and ability to carry out various activities.

The use of high-energy radiation from x-rays, gamma rays, neutrons, protons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body near cancer cells (internal radiation therapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that travels in the blood to tissues throughout the body. Also called irradiation and radiotherapy.

When referring to an experiment or clinical trial, the process by which animal or human subjects are assigned by chance to separate groups that compare different treatments or other interventions. Randomization gives each participant an equal chance of being assigned to any of the groups.

A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial.

Cancer that has recurred (come back), usually after a period of time during which the cancer could not be detected. The cancer may come back to the same place as the original (primary) tumor or to another place in the body. Also called recurrent cancer.

In oncology, a lymph node that drains lymph from the region around a tumor.

In medicine, an improvement related to treatment.

Looking back at events that have already taken place.

Treatment that is given when initial treatment (first-line therapy) doesn’t work, or stops working.

Cancer that begins in squamous cells, which are thin, flat cells that look like fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma.

The extent of a cancer in the body. Staging is usually based on the size of the tumor, whether lymph nodes contain cancer, and whether the cancer has spread from the original site to other parts of the body.

Stage II is divided into stages IIA and IIB. In stage IIA, (1) no tumor is found in the breast, but cancer is found in the axillary lymph nodes (the lymph nodes under the arm); or (2) the tumor is 2 centimeters or smaller and has spread to the axillary lymph nodes; or (3) the tumor is larger than 2 centimeters but not larger than 5 centimeters and has not spread to the axillary lymph nodes. In stage IIB, the tumor is either (1) larger than 2 centimeters but not larger than 5 centimeters and has spread to the axillary lymph nodes; or (2) larger than 5 centimeters but has not spread to the axillary lymph nodes.

Stage III breast cancer is divided into stages IIIA, IIIB, and IIIC. In stage IIIA, (1) no tumor is found in the breast, but cancer is found in axillary (under the arm) lymph nodes that are attached to each other or to other structures, or cancer may be found in lymph nodes near the breastbone; or (2) the tumor is 2 centimeters or smaller and cancer has spread to axillary lymph nodes that are attached to each other or to other structures, or the cancer may have spread to lymph nodes near the breastbone; or (3) the tumor is larger than 2 centimeters but not larger than 5 centimeters and cancer has spread to axillary lymph nodes that are attached to each other or to other structures or cancer may have spread to lymph nodes near the breastbone; or (4) the tumor is larger than 5 centimeters and cancer has spread to axillary lymph nodes that may be attached to each other or to other structures or the cancer may have spread to lymph nodes near the breastbone. In stage IIIB, the tumor may be any size and cancer (1) has spread to the chest wall and/or the skin of the breast; and (2) may have spread to axillary lymph nodes that may be attached to each other or to other structures or the cancer may have spread to lymph nodes near the breastbone. In stage IIIC, no tumor is found in the breast or the tumor may be any size and may have spread to the chest wall and/or the skin of the breast. Cancer has spread to lymph nodes above or below the collarbone and may have spread to axillary lymph nodes or to lymph nodes near the breastbone. In operable stage IIIC, the cancer (1) is found in ten or more axillary lymph nodes; or (2) is found in the lymph nodes below the collarbone; or (3) is found in axillary lymph nodes and in lymph nodes near the breastbone. In inoperable stage IIIC, the cancer has spread to the lymph nodes above the collarbone.

Describes a mathematical measure of difference between groups. The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone. Also called significant.

Cancer that forms in tissues lining the stomach. Also called gastric cancer.

Beneath the skin.

In a clinical study, the evaluation of results for some but not all of the patients who participated. The selected patients have one or more characteristics in common, such as the same stage of disease or the same hormone receptor status.

A procedure to remove or repair a part of the body or to find out whether disease is present. An operation.

Having to do with treating disease and helping healing take place.

An abnormal mass of tissue that results when cells divide more than they should or do not die when they should. Tumors may be benign (not cancerous), or malignant (cancerous). Also called neoplasm.

A nutrient that the body needs in small amounts to function and stay healthy. Sources of vitamins are plant and animal food products and dietary supplements. Some vitamins are made in the human body from food products. Vitamins are either fat-soluble (can dissolve in fats and oils) or water-soluble (can dissolve in water). Excess fat-soluble vitamins are stored in the body’s fatty tissue, but excess water-soluble vitamins are removed in the urine. Examples are vitamin A, vitamin C, and vitamin E.