FDA Approved Drugs
The following drugs have been approved since the year 2000 for the treatment of colorectal cancer:
Vectibix (panitumumab)
FDA approved September 2006
This drug is approved for the treatment of patients with colorectal cancer that has metastasized (spread to other parts of the body) following standard chemotherapy.
Vectibix, a monoclonal antibody that binds to a protein called epidermal growth factor receptor or EGFR on some cancer cells, received an accelerated approval after showing effectiveness in slowing tumor growth and, in some cases, reducing the size of the tumor.
FDA approved Vectibix on the basis of the results of a randomized, controlled clinical trial of 463 patients with metastatic cancer of the colon and the rectum after undergoing treatment with chemotherapy drugs, fluoropyrimidine, oxaliplatin and irinotecan.
The mean time to disease progression or death in patients receiving Vectibix was 96 days versus 60 days in patients receiving the best standard supportive care. In addition, 8 percent of the patients on Vectibix experienced a tumor shrinkage that in some cases exceeded 50 percent of the pre-treatment size of the tumor. Both study groups showed similar overall survival.
Under the accelerated approval program, drugs for serious and life-threatening diseases can be made available earlier in the development process if a promising effect of the drug is observed. As part of the approval, the manufacturer of Vectibix committed to conduct a postmarketing trial to show whether the drug improves patients’ survival in patients with fewer prior chemotherapies.
The most serious adverse events in the studies of Vectibix included pulmonary fibrosis, severe skin rash complicated by infections, infusion reactions, abdominal pain, nausea, vomiting and constipation. The most common adverse events associated with the drug included skin rash, fatigue, abdominal pain, nausea, and diarrhea.
Avastin (bevacizumab)
FDA approved February 2004
This drug is approved as a first-line treatment for patients with metastatic colorectal cancer -- cancer that has spread to other parts of the body.
Avastin, 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. Avastin 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.
Avastin 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 Avastin, it cannot stimulate the growth of blood vessels, thus denying tumors blood, oxygen and other nutrients needed for growth. Angiogenesis inhibitors such as Avastin 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.
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 Avastin was primarily shown in a randomized, double-blind clinical trial of more than 800 patients with metastatic colorectal cancer designed to find out whether Avastin extended the lives of patients. Roughly half the patients received IFL, the standard chemotherapy combination, and the other half received Avastin once every two weeks in addition to IFL. Overall, patients given Avastin 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% compared to 35% for the control arm of the trial.
Serious, but uncommon, side-effects of Avastin 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.
Erbitux (cetuximab)
FDA approved February 2004
This drug is approved to treat patients with advanced colorectal cancer that has spread to other parts of the body. Erbitux is the first monoclonal antibody approved to treat this type of cancer and is indicated as a combination treatment to be given intravenously with irinotecan, another drug approved to fight colorectal cancer, or alone if patients cannot tolerate irinotecan.
Erbitux was approved under FDA's accelerated approval program, which allows FDA to approve products for cancer and other serious or life-threatening diseases based on early evidence of a product's effectiveness. Although treatment with Erbitux has not been shown to extend patients' lives, it was shown to shrink tumors in some patients and delay tumor growth, especially when used as a combination treatment.
Erbitux is a genetically engineered version of a mouse antibody that contains both human and mouse components. (Antibodies in the body are substances produced by the immune system to fight foreign substances.) It can be produced in large quantities in the laboratory. This new monoclonal antibody is believed to work by targeting a natural protein called "epidermal growth factor receptor" (EGFR) on the surface of cancer cells, interfering with their growth.
For patients with tumors that express EGFR and who no longer responded to treatment with irinotecan alone or in combination with other chemotherapy drugs, the combination treatment of Erbitux and irinotecan shrank tumors in 22.9% of patients and delayed tumor growth by approximately 4.1 months. For patients who received Erbitux alone, the tumor response rate was 10.8% and tumor growth was delayed by 1.5 months.
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), and 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 efficacy and safety of Erbitux alone or in combination with irinotecan were studied in a randomized, controlled trial with 329 patients and also in combination with irinotecan in 138 patients in which all patients received both drugs. Erbitux was further evaluated as a single agent in a third clinical trial with 57 patients. Safety data from an additional 111 patients treated only with Erbitux was also evaluated. All of the trials included patients with EGFR-expressing metastatic colorectal cancer, whose disease had progressed after receiving irinotecan.
Two studies involving approximately 2000 patients are currently underway to assess the clinical benefits of Erbitux. These studies are specifically examining the ability of Erbitux to stop the progression of colorectal cancer and to extend the amount of time patients survive with the disease.
Erbitux can cause serious side-effects, usually during the administration of the first treatment, which may include difficulty breathing and low blood pressure. Infrequent interstitial lung disease (ILD) has been reported; however, it is difficult to determine if Erbitux caused ILD. ILD occurs when the lung becomes stiff due to scarring of the tissue between the air sacs of the lungs.
Other more common side-effects of Erbitux treatment include acne-like rash, dry skin, tiredness or weakness, fever, constipation, and abdominal pain.
Eloxatin (oxaliplatin)
FDA approved August 2002
This drug is approved for use in combination with infusional 5-fluorouracil (5-FU) and leucovorin for the treatment of patients with colorectal cancer whose disease has recurred or become worse following initial therapy with a combination of irinotecan with bolus 5-FU and leucovorin. The combination including Eloxatin was shown to shrink tumors in some patients and delay resumed tumor growth. There are as yet no data on the effects of the combination on survival.
A multi-center, randomized, controlled study compared the effectiveness and safety of Eloxatin alone, infusional 5-FU/leucovorin alone (a standard type of treatment for colorectal cancer), and the combination of these two treatments in patients who had either relapsed, or progressed while on or shortly after standard treatment. Although the individual drugs had very little effect, the combination resulted in a greater number of patients having tumor shrinkage and led to a delay in resumption of cancer growth.
Eloxatin is intended for use by physicians experienced in the use of cancer agents. A black box warning detailing this use and highlighting anaphylactic-like reactions associated with Eloxatin is included in the labeling. Eloxatin can have a toxic effect on nerve endings that may result in either an acute or cumulative pattern of side effects. This may result in the feeling of numbness or tingling, especially in the hands or feet or around the mouth or throat. For some patients these symptoms may be worsened by exposure to cold. This side effect usually occurs within hours or days of dosing. Another side effect is impairment in performing ordinary daily tasks such as difficulty buttoning clothes. This condition generally improves after the treatment is complete.
Other common side effects of Eloxatin are vomiting, diarrhea, anemia, increased risk of bleeding or infection, or allergic reaction. Women should be advised to avoid becoming pregnant while receiving this treatment, because it may cause harm to the fetus.
Xeloda (capecitabine)
FDA approved April 2001
This drug is a type of chemotherapy for treating colon cancer. Capecitabine interferes with the growth of cancer cells and decreases the size of the tumor.