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Brand name(s): Avastin®

• Approved for Metastatic Renal Cell Carcinoma
• Approved for Second-Line Treatment of Glioblastoma
• Approved for Metastatic HER2 Negative Breast Cancer
• Approved for First-Line Treatment of Non-Small Cell Lung Cancer (NSCLC)
• Approved for Second-Line Treatment of Metastatic Colorectal Cancer
• Approved for First-Line Treatment of Metastatic Colorectal Cancer
• Drug Warnings Issued

Full prescribing information ⁶ is available including clinical trial information, safety, dosing, drug-drug interactions, and contraindications.

Metastatic Renal Cell Carcinoma

On July 31, 2009, the FDA granted approval for the use of Bevacizumab (Avastin®, made by Genentech, Inc.) in combination with interferon alfa for the treatment of patients with metastatic renal cell carcinoma. The approval was based on results from the BO17705 trial, which demonstrated a 5-month improvement in median progression-free survival (PFS) in patients treated with bevacizumab.

The BO17705 trial was a randomized, double-blind, placebo-controlled, multinational clinical trial conducted in patients with metastatic renal cell carcinoma who had undergone nephrectomy. The study compared the combination of bevacizumab plus interferon alfa-2a to interferon alfa-2a plus placebo. This trial was conducted by Hoffmann-La-Roche in Europe, Asia, and Australia. The primary outcome measure of the trial, assessed by study investigators, was PFS. The determination of PFS by an independent review committee, blinded to treatment assignment, supported the investigators' PFS assessment.

A total of 649 patients (327 treated with bevacizumab plus interferon, 322 treated with interferon plus placebo) were enrolled. The median PFS was 10.2 months for the bevacizumab plus interferon arm compared to 5.4 months for the interferon and placebo arm [hazard ratio (HR), 0.60 (95 percent CI: 0.49, 0.72), p < 0.0001]. The independent review committee's analysis of 569 patients with radiographs available for review yielded similar results [median PFS, 10.4 versus 5.5 months; HR, 0.57 (95 percent CI: 0.45, 0.72)].

The BO17705 trial did not demonstrate a statistically significant advantage in overall survival for patients treated with bevacizumab plus interferon compared with patients who received interferon plus placebo treatment [HR, 0.86 (95 percent CI: 0.72, 1.04), p= 0.13].

Additional support for the results of the BO17705 trial was provided by the published results of the 90206 trial, a randomized, open-label study of bevacizumab plus interferon alfa-2b compared with interferon alfa-2b alone in patients with metastatic renal cell carcinoma. The Cancer and Leukemia Group B conducted this trial in North America. A similar prolongation in PFS was reported in the 90206 trial with a median PFS of 8.4 months for patients treated with the bevacizumab combination versus 4.9 months for patients who received single-agent interferon alfa-2b. An improvement in overall survival was not observed.

In the BO17705 trial, the combination of bevacizumab plus interferon alfa-2a resulted in a higher overall incidence of toxicities, and more severe toxicities, than observed with interferon alfa-2a alone.

Serious adverse events were reported in 31 percent of patients treated with bevacizumab plus interferon and in 19 percent of patients treated with interferon plus placebo. NCI CTCAE grade 3 and greater adverse events were reported in 63 percent of patients treated with bevacizumab plus interferon versus 47 percent of patients who received interferon plus placebo. Grade 3 and greater adverse events attributable to bevacizumab (≥ 2 percent greater incidence in the bevacizumab plus interferon arm compared with the interferon plus placebo arm) included bleeding, hypertension, proteinuria, and venous or arterial thrombosis. Two patients with grade 5 bleeding events (ruptured aneurysm and hemoptysis), two patients with hypertensive encephalopathy, and four patients with grade 4 pulmonary embolism were reported among those who were treated with bevacizumab plus interferon.

The most common bevacizumab-related toxicities were bleeding/hemorrhage, hypertension, proteinuria and venous or arterial thromboembolic events. Among the 20 percent of patients with reports of proteinuria, the median onset of proteinuria was 5.6 months (range, 15 days to 37 months) after initiation of bevacizumab. The median time-to-resolution was 6.1 months. Proteinuria did not resolve in 40 percent of patients after a median follow-up of 11.2 months. Bevacizumab was permanently discontinued in 30 percent of the patients who developed proteinuria.

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Second-Line Treatment of Glioblastoma

On May 5, 2009, the FDA granted accelerated approval to bevacizumab injection (Avastin®, made by Genentech, Inc.) as a single agent for patients with glioblastoma, with progressive disease following prior therapy. The approval was based on demonstration of durable objective response rates observed in two single-arm trials, AVF3708g and NCI 06-C-0064E.

AVF3708g was an open-label, multi-center trial of randomly assigned patients with previously treated glioblastoma. Patients received bevacizumab (10 mg/kg IV) alone or bevacizumab plus irinotecan every 2 weeks until disease progression or unacceptable toxicity was noted. All patients received prior radiotherapy and temozolomide. Patients completed radiotherapy at least 8 weeks prior to receiving bevacizumab. Patients with active brain hemorrhage were excluded. Only efficacy data from the bevacizumab monotherapy arm (N=85) was used to support drug approval.

The efficacy of bevacizumab was demonstrated using response assessment based on WHO radiographic criteria. In addition, all responding patients must have had stable or decreasing corticosteroid use. Responses were observed in 25.9 percent (95 percent CI: 17.0 percent, 36.1 percent) of the patients. Median response duration was 4.2 months (95 percent CI: 3.0, 5.7 months). Radiologic assessment was performed using MR imaging (T1 and T2/FLAIR). MRI does not necessarily distinguish between tumor, edema and radiation necrosis.

NCI 06-C-0064E was a single-arm, single-site study of bevacizumab for the treatment of patients with previously treated gliomas. The study enrolled 56 patients with glioblastoma. All patients had documented disease progression after receiving temozolomide and radiation therapy. Patients received bevacizumab (10 mg/kg IV) every 2 weeks until disease progression or unacceptable toxicity was noted.

The objective response rate from the NCI 06-C-0064E study was 19.6 percent (95 percent CI: 10.9 percent, 31.3 percent), using the same response criteria as in AVF3708g. Median response duration was 3.9 months (95 percent CI: 2.4, 17.4).

Safety data was provided for study AVF3708g. In patients receiving bevacizumab monotherapy, the most frequently reported adverse events of any grade were infection, fatigue, headache, hypertension, epistaxis, and diarrhea. Bevacizumab was discontinued due to adverse events in 4.8 percent of patients. Two deaths (one retroperitoneal hemorrhage and one neutropenic infection) were possibly related to bevacizumab.

Grade 3-5 bevacizumab-related adverse events included bleeding/hemorrhage, CNS hemorrhage, hypertension, venous and arterial thromboembolic events, wound-healing complications, proteinuria, gastrointestinal perforation and reversible posterior leukoencephalopathy (RPLS). The attribution of certain adverse events (e.g., CNS hemorrhage, wound healing complications, and thromboembolic events) to either bevacizumab, underlying disease status, or both cannot be determined due to the single-arm, non-comparative study design.

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Metastatic HER2-Negative Breast Cancer

On February 22, 2008, the FDA granted accelerated approval for bevacizumab (Avastin®, made by Genentech) to be used in combination with paclitaxel (Taxol®) for the treatment of patients who have not received chemotherapy for metastatic HER2-negative breast cancer.

The approval was based on the demonstration of an improvement in progression-free survival (PFS) in patients receiving bevacizumab with paclitaxel compared to those receiving paclitaxel alone as a first-line treatment for metastatic breast cancer. No data are currently available that demonstrate an improvement in disease-related symptoms or increased overall survival with bevacizumab in breast cancer.

The efficacy and safety of bevacizumab as first-line treatment of patients with metastatic breast cancer was studied in a single, open-label, randomized, multicenter study (Study 7 or E2100). Patients who had not received chemotherapy for locally recurrent or metastatic breast cancer were randomized to receive either paclitaxel (N=354 patients) alone at 90 mg/m2 weekly for three doses with one week rest (28-day cycle) or in combination with bevacizumab 10 mg/kg every 14 days (N=368 patients). Patients with HER2-overexpressing breast cancer were not eligible unless they had received prior therapy with trastuzumab (Herceptin®).

The addition of bevacizumab to paclitaxel resulted in an improvement in PFS with no significant improvement in overall survival. The median PFS was 11.3 months (95 percent CI 10.5,13.3) and 5.8 months (95 percent CI 5.4, 8.2) months for the bevacizumab plus paclitaxel arms versus the paclitaxel alone, respectively (p<0.0001, HR 0.48, 95 percent CI 0.39, 0.61) Partial response rates in patients with measurable disease were higher with bevacizumab plus paclitaxel: 48.9 percent versus 22.2 percent (p<0.001). No complete responses were observed.

The efficacy and safety of bevacizumab as a second and third line treatment of patients with metastatic breast cancer were studied in a single open-label randomized study (Study 8 or AVF2119). Patients who had received prior anthracycline and taxane therapy in the adjuvant setting or for their metastatic breast cancer were randomized to receive either capecitabine alone or in combination with bevacizumab. The study enrolled 462 patients. The study failed to demonstrate a statistically significant effect on PFS or overall survival. The product labeling specifies that bevacizumab is not indicated for patients with breast cancer that has progressed following anthracycline and taxane chemotherapy administered for metastatic disease.

Data collection in Trial 7 was limited to NCI-CTC grade 3-5 non-hematologic and Grade 4-5 hematologic adverse events. A 20 percent increase in grade 3-5 adverse events was observed in the bevacizumab plus paclitaxel arm compared to paclitaxel alone. Severe and life-threatening adverse events occurring more frequently on the bevacizumab-containing arm included sensory neuropathy, hypertension, fatigue, infection without neutropenia, neutropenia, vomiting, diarrhea, bone pain, headache, proteinuria, and cerebrovascular ischemia. Fatal adverse reactions occurred in 6 of 363 (1.7 percent) of patients who received paclitaxel plus bevacizumab. Causes of death were gastrointestinal perforation (two patients), myocardial infarction (two patients), diarrhea/abdominal pain/weakness/hypotension (two patients).

The most serious, and sometimes fatal, bevacizumab adverse events have been previously described in product labeling and include gastrointestinal perforation, wound healing complications, hemorrhage, arterial thromboembolic events, hypertensive crisis, nephrotic syndrome, congestive heart failure, and neutropenic sepsis. The most common bevacizumab adverse events previously described in product labeling include asthenia, pain, abdominal pain, headache, hypertension, diarrhea, nausea, vomiting, anorexia, stomatitis, constipation, upper respiratory infection, epistaxis, dyspnea, exfoliative dermatitis, and proteinuria.

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First-Line Treatment of Non-Small Cell Lung Cancer (NSCLC)

On October 11, 2006, the FDA granted approval for a labeling extension for bevacizumab (Avastin®, Genentech, Inc.), administered in combination with carboplatin and paclitaxel, for the initial systemic treatment of patients with unresectable, locally advanced, recurrent, or metastatic, non-squamous, non-small cell lung cancer. This recommendation is based on the demonstration of a statistically significant improvement in overall survival (OS) in patients receiving bevacizumab with carboplatin and paclitaxel compared to those receiving carboplatin and paclitaxel alone.

The primary trial (E4599) supporting this approval was a randomized, active controlled, open label, multi-center clinical trial evaluating bevacizumab plus carboplatin and paclitaxel (n=434) versus carboplatin and paclitaxel alone (n=444). (See the protocol summary ⁷.)

Patients with squamous histology, mixed cell tumors with predominant squamous cell histology, central nervous system metastases, gross hemoptysis (>1/2 tsp red blood), or unstable angina and those receiving therapeutic anticoagulation were excluded from the trial. Patients with squamous cell histology were excluded based on four patients with life-threatening or fatal hemoptysis among 13 patients with squamous cell histology enrolled in a randomized, active-control, phase II study (AVF0757g) who received chemotherapy with bevacizumab.

Among the 878 randomized patients, the median age was 63, 46 percent were female, no patients had received prior chemotherapy, 76 percent had stage IV disease, 12 percent had stage IIIB disease with malignant pleural effusion, 11 percent had recurrent disease, and 40 percent had an ECOG performance status of 0.

OS, the primary endpoint, was significantly longer in patients receiving bevacizumab in combination with paclitaxel and carboplatin as compared to those receiving paclitaxel and carboplatin alone (median OS 12.3 vs 10.3 mos; hazard ratio 0.80, p=0.013 stratified log rank test). Although a consistent effect was observed across most subgroups, in an exploratory analysis, evidence of a survival benefit was not observed in women (HR 0.99; 95 percent CI 0.79, 1.25).

In E4599, data collection was limited to NCI-CTC grade 3-5 adverse events. Severe and life-threatening adverse events occurring more frequently in patients receiving bevacizumab and chemotherapy were

• neutropenia (27 percent vs. 17 percent)
• fatigue (16 percent vs. 13 percent)
• hypertension (8 percent vs. 0.7 percent)
• infection without neutropenia (7 percent vs. 3 percent)
• thrombosis/embolism (5 percent vs. 3 percent)
• pneumonitis or pulmonary infiltrate (5 percent vs. 3 percent)
• infection with grade 3 or 4 neutropenia (5 percent vs. 2 percent)
• febrile neutropenia (5 percent vs. 2 percent)
• hyponatremia (4 percent vs. 1 percent)
• proteinuria (3 percent vs. 0)
• headache (3 percent vs. 0.5 percent)
Fatal, treatment-related adverse events in patients receiving bevacizumab were pulmonary hemorrhage (2.3 percent vs. 0.5 percent), gastrointestinal hemorrhage CNS infarction, gastrointestinal perforation, myocardial infarction, and neutropenic sepsis.

The most serious, and sometimes fatal, bevacizumab toxicities are gastrointestinal perforation, wound healing complications, hemorrhage, arterial thromboembolic events, hypertensive crisis, nephrotic syndrome, congestive heart failure, and neutropenic sepsis. The most common adverse events in patients receiving bevacizumab are asthenia, pain, abdominal pain, headache, hypertension, diarrhea, nausea, vomiting, anorexia, stomatitis, constipation, upper respiratory infection, epistaxis, dyspnea, exfoliative dermatitis, and proteinuria.

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Second-Line Treatment of Metastatic Colorectal Cancer

On June 20, 2006, the FDA granted approval for a labeling extension for bevacizumab (Avastin®, made by Genentech), administered in combination with intravenous 5-fluorouracil-based chemotherapy, for the second-line treatment of metastatic carcinoma of the colon or rectum. This recommendation is based on the demonstration of a statistically significant improvement in overall survival (OS) in patients receiving bevacizumab plus FOLFOX4 (5-flourouracil, leucovorin, and oxaliplatin) when compared to those receiving FOLFOX4 alone.

The trial (E3200) supporting this approval was an openlabel, randomized, three-arm, active-controlled, multicenter clinical trial evaluating bevacizumab alone (n=244), bevacizumab plus FOLFOX4 (n=293), and FOLFOX4 alone (n=292). Following a planned interim analysis, the bevacizumab monotherapy arm was closed to accrual based on evidence of decreased survival in patients treated with bevacizumab alone compared with FOLFOX4 alone.

Patients entered on the trial had progressive or recurrent disease following prior 5-FU and irinotecan-based therapy. Patients (99 percent) received irinotecan with or without 5-FU as initial therapy for metastatic disease; those who received adjuvant irinotecan-based chemotherapy were required to have recurred within six months of completing therapy.

In both the combination and monotherapy arms, bevacizumab was administered at a dose of 10 mg/kg every two weeks. The FOLFOX4 regimen, administered every two weeks, consisted of oxaliplatin 85 mg/m2 and leucovorin 200 mg/m2 administered concurrently as an intravenous infusion, then 5FU 400 mg/m2 IV bolus followed by 5FU 600 mg/m2 continuous intravenous infusion on Day 1. On Day 2, patients received leucovorin 200 mg/m2 IV, then 5FU 400 mg/m2 IV bolus followed by 5FU 600 mg/m2 continuous intravenous infusion. When given in combination with FOLFOX4, bevacizumab was administered on Day 1 prior to oxaliplatin and leucovorin.

Among the 829 randomized patients, the median age was 61 years and 49 percent had an ECOG performance status of 0. Twenty-six percent had received prior radiation therapy, 80 percent received prior adjuvant chemotherapy, and all received prior irinotecan therapy.

Overall survival, the trial’s primary endpoint, was significantly longer in patients receiving bevacizumab in combination with FOLFOX4 as compared to those receiving FOLFOX4 alone (median overall survival was 13.0 months vs. 10.8 months; hazard ratio 0.75, p=0.001 stratified log rank test). The survival benefit was also observed in subgroups defined by age (<65 vs. >65 yrs) and gender. Patients treated with the bevacizumab combination were reported by investigator assessment to have significantly longer progression-free survival and higher overall response rate.

The most serious, and sometimes fatal, bevacizumab toxicities are gastrointestinal perforation, wound healing complications, hemorrhage, arterial thromboembolic events, hypertensive crisis, nephrotic syndrome and congestive heart failure. The monthst common adverse events in patients receiving bevacizumab are asthenia, pain, abdominal pain, headache, hypertension, diarrhea, nausea, vomiting, anorexia, stomatitis, constipation, upper respiratory infection, epistaxis, dyspnea, exfoliative dermatitis, and proteinuria.

In Trial E3200, data were collected only for NCI-CTC grade 3-5 adverse events. Therefore, these data are likely to under-estimate the true adverse event rates. In addition, neither the time of onset nor the time to resolution of adverse events were collected.

NCI-CTC grade 3-5 adverse events that were more common in patients receiving the bevacizumab compared to FOLFOX4 alone were

• fatigue (19 percent vs. 13 percent)
• diarrhea (18 percent vs. 13 percent)
• sensory neuropathy (17 percent vs. 9 percent)
• nausea (12 percent vs. 5 percent)
• vomiting (11 percent vs. 4 percent)
• dehydration (10 percent vs. 5 percent)
• hypertension (9 percent vs. 2 percent)
• abdominal pain (8 percent vs. 5 percent)
• hemorrhage (5 percent vs. 1 percent)
• other neurologic toxicities (5 percent vs. 3 percent)
• ileus (4 percent vs. 1 percent)
• headache (3 percent vs. 0)

Fatal, treatment-related adverse events in patients receiving bevacizumab in this study included CNS hemorrhage, gastrointestinal hemorrhage, and gastrointestinal perforation with sepsis.

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First-Line Treatment of Metastatic Colorectal Cancer

On February 26, 2004, the FDA approved bevacizumab (Avastin®, a trademark of Genentech, Inc.) as a first-line treatment for patients with metastatic colorectal cancer - cancer that has spread to other parts of the body. Bevacizumab, a monoclonal antibody, is the first product to be approved that works by preventing the formation of new blood vessels, a process known as angiogenesis.

Bevacizumab was shown to extend patients' lives by about five months when given intravenously as a combination treatment along with standard chemotherapy drugs for colon cancer (the "Saltz regimen" also known as IFL). IFL treatment includes ironotecan, 5-fluorouracil (5FU) and leucovorin.

Bevacizumab is a genetically engineered version of a mouse antibody that contains both human and mouse components. (Antibodies are substances produced by the body's immune system to fight foreign substances.) Special technology also allows it to be produced in large quantities in the laboratory.

This new monoclonal antibody is believed to work by targeting and inhibiting the function of a natural protein called "vascular endothelial growth factor" (VEGF) that stimulates new blood vessel formation. When VEGF is targeted and bound to bevacizumab, it cannot stimulate the growth of blood vessels, thus denying tumors blood, oxygen and other nutrients needed for growth.

Angiogenesis inhibitors such as bevacizumab have been studied, first in the laboratory and then in patients, for three decades with the hope they might prevent the growth of cancer. This is the first such product that has been proven to delay tumor growth and more importantly, significantly extend the lives of patients.

"The approval of [bevacizumab] is the result of many years of research and development exploring a promising new approach to fighting cancer, and it is one of a number of recent new treatments for colorectal cancer that taken together, have significantly improved the armamentarium for fighting this disease," said Mark B. McClellan, M.D., Ph.D., FDA Commissioner. "These medical achievements reflect the innovation of drug developers and the hard work of FDA's cancer review teams, and they are proof of the promise offered by biomedical innovation. The dedication of everyone involved in these efforts is making a real difference in the lives of cancer patients."

Colorectal cancer - cancer of the colon or rectum - is the third most common cancer affecting men and women in the U.S. and, according to the Centers for Disease Control and Prevention (CDC), is the second leading cause of cancer-related death. Colorectal cancer is also one of the most commonly diagnosed cancers in the U.S.; approximately 147,500 new cases were diagnosed in 2003.

The safety and efficacy of bevacizumab was primarily shown in a randomized, double-blind clinical trial of more than 800 patients with metastatic colorectal cancer designed to find out whether bevacizumab extended the lives of patients. Roughly half the patients received IFL, the standard chemotherapy combination, and the other half received bevacizumab once every two weeks in addition to IFL.

Overall, patients given bevacizumab in combination with IFL survived about five months longer and the average time before tumors started regrowing or new tumors appeared was four months longer than patients receiving IFL alone. The overall response rate to the treatment was 45 percent compared to 35 percent for the control arm of the trial.

Serious, but uncommon, side-effects of bevacizumab include formation of holes in the colon (gastrointestinal perforation) generally requiring surgery and sometimes leading to intra-abdominal infections, impaired wound healing, and bleeding from the lungs or internally. Other, more common, side-effects are high blood pressure, tiredness, blood clots, diarrhea, decreased white blood cells (lowering immunity to diseases) headache, appetite loss and mouth sores.

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Drug Warnings Issued

On August 12, 2004, the FDA and Genentech, Inc. issued an important drug warning ⁸ to healthcare providers that there is evidence of an increased risk of serious arterial thromboembolic events, including cerebrovascular accident, myocardial infarctions, transient ischemic attacks, and angina related to bevacizumab. The risk of fatal arterial thrombotic events is also increased. In randomized, active-controlled studies conducted in patients with metastatic colorectal cancer, the risks of a serious arterial thrombotic event was approximately two-fold higher in patients receiving infusional 5-FU based chemotherapy plus bevacizumab, with an estimated overall rate of up to 5 percent.

On September 27, 2006, the FDA and Genentech, Inc. issued another important drug warning ⁹ to healthcare providers that, for patients taking bevacizumab, there is evidence of an increased risk of reversible posterior leukoencephalopathy syndrome (RPLS), a rare brain-capillary leak syndrome associated with hypertension, fluid retention, and cytotoxic effects of immunosuppressive drugs on the vascular endothelium. There is also an increased risk of nasal septum perforation, so prescribing information has been revised to include that serious adverse effect.

On September 24, 2007, the FDA issued a safety labeling update. The updated prescribing information notes that non-gastrointestinal fistula formation has been reported in patients treated with bevacizumab in controlled clinical studies (with an incidence of < 0.3%) and in post-marketing experience, in some cases with fatal outcome. Fistula formation involving the following areas of the body other than the gastrointestinal tract has been reported: tracheo-esophageal, bronchopleural, biliary, vaginal, and bladder. Events were reported throughout treatment with bevacizumab, with most events occurring within the first six months. Physicians are instructed to permanently discontinue bevacizumab in patients with fistula formation involving an internal organ.

This summary was provided by Richard Pazdur, M.D., director of the FDA's Division of Oncology Drug Products.

The FDA is the division of the U.S. Department of Health and Human Services charged with ensuring the safety and effectiveness of new drugs and other products. (See "Understanding the Approval Process for New Cancer Treatments ¹⁰.") The FDA's mission is to promote and protect the public health by helping safe and effective products to reach the market in a timely way, and monitoring products for continued safety after they are in use.

Glossary Terms

A substance that may prevent the formation of blood vessels. In anticancer therapy, an angiogenesis inhibitor may prevent the growth of new blood vessels that tumors need to grow.

An abnormal loss of the appetite for food. Anorexia can be caused by cancer, AIDS, a mental disorder (i.e., anorexia nervosa), or other diseases.

A type of antibiotic that comes from certain types of Streptomyces bacteria. Anthracyclines are used to treat many types of cancer. Anthracyclines damage the DNA in cancer cells, causing them to die. Daunorubicin, doxorubicin, and epirubicin are anthracyclines.

Having to do with the liver, bile ducts, and/or gallbladder.

The organ that stores urine.

A drug used to treat stage III colon cancer in patients who had surgery to remove the cancer. It is also used to treat metastatic breast cancer that has not improved after treatment with certain other anticancer drugs. Capecitabine is being studied in the treatment of other types of cancer. It is taken up by cancer cells and breaks down into 5-fluorouracil, a substance that kills tumor cells. Capecitabine is a type of antimetabolite. Also called Xeloda.

A condition in which fluid and proteins leak out of tiny blood vessels and flow into surrounding tissues, resulting in dangerously low blood pressure. Capillary leak syndrome may lead to multiple organ failure and shock.

The disappearance of all signs of cancer in response to treatment. This does not always mean the cancer has been cured. Also called complete remission.

Weakness of the heart muscle that leads to a buildup of fluid in body tissues.

Any steroid hormone made in the adrenal cortex (the outer part of the adrenal gland). They are also made in the laboratory. Corticosteroids have many different effects in the body, and are used to treat many different conditions. They may be used as hormone replacement, to suppress the immune system, and to treat some side effects of cancer and its treatment. Corticosteroids are also used to treat certain lymphomas and lymphoid leukemias.

Cell-killing.

Inflammation of the skin.

Difficult, painful breathing or shortness of breath.

A block in an artery caused by blood clots or other substances, such as fat globules, infected tissue, or cancer cells.

A disorder of the brain that can be caused by disease, injury, drugs, or chemicals.

Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach.

A condition marked by fever and a lower-than-normal number of neutrophils in the blood. A neutrophil is a type of white blood cell that helps fight infection. Having too few neutrophils increases the risk of infection.

Initial treatment used to reduce a cancer. First-line therapy is followed by other treatments, such as chemotherapy, radiation therapy, and hormone therapy to get rid of cancer that remains. Also called induction therapy, primary therapy, and primary treatment.

An abnormal opening or passage between two organs or between an organ and the surface of the body. Fistulas may be caused by injury, infection, or inflammation, or may be created during surgery.

Refers to the stomach and intestines. Also called GI.

The stomach and intestines. The gastrointestinal tract is part of the digestive system, which also includes the salivary glands, mouth, esophagus, liver, pancreas, gallbladder, and rectum.

A fast-growing type of central nervous system tumor that forms from glial (supportive) tissue of the brain and spinal cord and has cells that look very different from normal cells. Glioblastoma usually occurs in adults and affects the brain more often than the spinal cord. Also called GBM, glioblastoma multiforme, and grade IV astrocytoma.

Coughing or spitting up blood from the respiratory tract.

In medicine, loss of blood from damaged blood vessels. A hemorrhage may be internal or external, and usually involves a lot of bleeding in a short time.

A protein involved in normal cell growth. It is found on some types of cancer cells, including breast and ovarian. Cancer cells removed from the body may be tested for the presence of HER2/neu to help decide the best type of treatment. HER2/neu is a type of receptor tyrosine kinase. Also called c-erbB-2, human EGF receptor 2, and human epidermal growth factor receptor 2.

Abnormally low blood pressure.

Describes the ability to decrease the body's immune system responses.

The number of new cases of a disease diagnosed each year.

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.

Into or within a vein. Intravenous usually refers to a way of giving a drug or other substance through a needle or tube inserted into a vein. Also called IV.

The active ingredient in a drug used alone or in combination with other drugs to treat colon cancer or rectal cancer that has spread to other parts of the body or has come back after treatment with fluorouracil. It is also being studied in the treatment of other types of cancer. Irinotecan blocks certain enzymes needed for cell division and DNA repair, and it may kill cancer cells. It is a type of topoisomerase inhibitor and a type of camptothecin analog.

A tumor that can be accurately measured in size. This information can be used to judge response to treatment.

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

A type of protein made in the laboratory that can locate and bind to substances in the body, including tumor cells. There are many kinds of monoclonal antibodies. Each monoclonal antibody is made to find one substance. Monoclonal antibodies are being used to treat some types of cancer and are being studied in the treatment of other types. They can be used alone or to carry drugs, toxins, or radioactive materials directly to a tumor.

Having to do with nerves or the nervous system.

A nerve problem that causes pain, numbness, tingling, swelling, or muscle weakness in different parts of the body. It usually begins in the hands or feet and gets worse over time. Neuropathy may be caused by physical injury, infection, toxic substances, disease (such as cancer, diabetes, kidney failure, or malnutrition), or drugs, including anticancer drugs. Also called peripheral neuropathy.

A condition in which there is a lower-than-normal number of neutrophils (a type of white blood cell).

A measurable response.

In biology, to make too many copies of a protein or other substance. Overexpression of certain proteins or other substances may play a role in cancer development.

A decrease in the size of a tumor, or in the extent of cancer in the body, in response to treatment. Also called partial remission.

A measure of how well a patient is able to perform ordinary tasks and carry out daily activities.

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.

An abnormal collection of fluid between the thin layers of tissue (pleura) lining the lung and the wall of the chest cavity.

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 length of time during and after treatment in which a patient is living with a disease that does not get worse. Progression-free survival may be used in a clinical study or trial to help find out how well a new treatment works. Also called PFS.

Having to do with the lungs.

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 radiotherapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that travels in the blood to tissues throughout the body. Also called irradiation and radiation therapy.

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 recurrence.

The most common type of kidney cancer. It begins in the lining of the renal tubules in the kidney. The renal tubules filter the blood and produce urine. Also called hypernephroma.

The percentage of patients whose cancer shrinks or disappears after treatment.

The presence of bacteria or their toxins in the blood or tissues.

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.

Inflammation or irritation of the mucous membranes in the mouth.

A type of drug that blocks cell growth by stopping mitosis (cell division). Taxanes interfere with microtubules (cellular structures that help move chromosomes during mitosis). They are used to treat cancer. A taxane is a type of mitotic inhibitor and antimicrotubule agent.

A drug that is used to treat certain types of brain tumors in adults and is being studied in the treatment of other types of cancer. It belongs to the family of drugs called alkylating agents. Also called Temodar.

The formation or presence of a thrombus (blood clot) inside a blood vessel.

A monoclonal antibody that binds to HER2 (human epidermal growth factor receptor 2), and can kill HER2-positive cancer cells. Monoclonal antibodies are made in the laboratory and can locate and bind to substances in the body, including cancer cells. Trastuzumab is used to treat breast cancer that is HER2-positive and has spread after treatment with other drugs. It is also used with other anticancer drugs to treat HER2-positive breast cancer after surgery. Trastuzumab is also being studied in the treatment of other types of cancer. Also called Herceptin.

Unable to be removed with surgery.

Having to do with the vagina (the birth canal).

A substance made by cells that stimulates new blood vessel formation. Also called vascular endothelial growth factor.