Colorectal Cancer Chemotherapy Drugs

My son-in-law died last April after being diagnosed with stage IV colon cancer in 2010. Our family were all very devastated, since he was only 51 years old. Several chemotherapeutic regimens were tried by oncologists here in Northern California,in the most prestigious oncology treatment Research Center. The drugs tried did prolong his life for almost 2 years, but at the end, not one of the several experimental drugs saved his life, since he was already in stage IV when he was diagnosed. I had a feeling that my son-in-law could have survived the disease if he was diagnosed earlier, perhaps stage II or even III for the for therapy to be effective. My son-in-law left a 9-year old daughter and a 47-year old widow, because cancer sucks and kills if not diagnosed early. Please have a yearly physical check up even if you are feeling well.

This personal experience inspired me to do some web search on the drugs approved and what is in the pipeline for the treatment of colon cancer here in the US. The article is as follows:

Seven drugs are currently approved by FDA for colorectal cancer chemotherapy:

5-fluorouracil (5-FU, Adrucil), which is often given in combination with leucovorin

(Wellcovorin). Leucovorin is a vitamin that helps boost the effectiveness of 5-FU.

Capecitabine (Xeloda)

Oxaliplatin (Eloxatin)

Irinotecan (Camptosar)

Bevacizumab (Avastin)

Cetuximab (Erbitux)

Panitumumab (Vectibix)

Capecitabine is a pill form of 5-FU. The other drugs are administered intravenously. Many of these drugs are given in combination with each other. Common chemotherapy combination regimens include: 5-FU / LV (5-FU and leucovorin), FOLFOX (5-FU with leucovorin and oxaliplatin), FOLFORI (5-FU with leucovorin and irinotecan), IFL (Irinotecan, 5-FU, leucovorin), and XELOX (Capecitabine and oxaliplatin).

Side effects occur with all chemotherapeutic drugs. They are more severe with higher doses and increase over the course of treatment. Because cancer cells grow and divide rapidly, chemotherapy drugs work by killing fast-growing cells. This means that healthy cells that multiply quickly can also be affected. The fast-growing normal cells most likely to be affected are blood cells forming in the bone marrow, and cells in the digestive tract, reproductive system, and hair follicles. Nausea and vomiting is a very common side effect, but drugs such as ondansetron (Zofran) can help provide relief. In general, side effects are nearly always temporary, and medications can help manage them. Most patients are able to continue with normal activities for all but perhaps 1 - 2 days a month.

Specific Chemotherapy Drugs

5-Fluorouracil(5-FU) with Leucovorin. Adjuvant (following surgery) chemotherapy using 5-fluorouracil, either alone or with leucovorin (5-FU/LV), is the standard treatment for patients with high-risk colon cancer (Stage III or select patients with Stage II tumors). Leucovorin, also called folinic acid, is a form of the B vitamin folic acid, which helps increase 5-FU’s effectiveness. Patients are given a series of cycles that usually continue for at least 6 months.

There are many different ways of giving 5-FU, including intravenously over several hours once a week, intravenously daily for 5 consecutive days every month, or as continuous infusion with a portable pump. The most common side effects include nausea and vomiting, diarrhea, loss of appetite, hair loss, swelling of hands and feet, rashes, and mouth sores.

Studies indicate that bevacizumab administered intravenously along with IFL extends survival by about 5 months longer than IFL alone. Common side effects of bevacizumab include nosebleeds, fatigue, diarrhea, and high blood pressure. Less common side effects include stroke, heart attacks, angina, and formation of holes in the colon and stomach (gastrointestinal perforation).

Cetuximab. Cetuximab (Erbitux) was approved in 2004 for the treatment of metastatic colorectal cancer. This monoclonal antibody drug targets epidermal growth factor receptor (EGFR), a protein required by cancer cells in order to proliferate. It can be used either in combination with irinotecan or alone for patients who have not responded to irinotecan. Studies of the cetuximab-irinotecan combination suggest it can help in tumor shrinkage. It has a modest effect on survival, prolonging patients' lives by about an additional month or two. Recent guidelines recommend that cetuximab, and panitumumab (see below), should be given only to patients with tumors that express the wild-type KRAS gene. Patients with metastatic cancer should have tumors tested for KRAS gene status.

Panitumumab . Panitumumab (Vectibix) was approved in 2006 for treatment of colorectal cancer that has metastasized following standard chemotherapy. Like cetuximab, panitumumab is a monoclonal antibody drug that targets EGFR. In clinical trials, panitumumab helped delay disease progression and prolong survival by about 3 months. About 8% of patients experienced tumor shrinkage. Common side effects of this drug include skin rash, fatigue, abdominal pain, nausea, and diarrhea or constipation. Serious side effects include pulmonary fibrosis, severe skin rash, and skin reactions at the infusion site.

Investigational Biologic Drugs

One of the most promising recent developments in cancer treatment research has been the emergence of so-called "targeted therapies." Traditional chemotherapy drugs can be effective, but because they do not distinguish between healthy and cancerous cells their generalized toxicity can cause severe side effects. Targeted therapies work on a molecular level by blocking specific mechanisms associated with cancer cell growth and division.

Many targeted therapies are classified as biologic drugs. Bevacizumab (Avastin), cetixumab (Erbitux), and panitumumab (Vectibix) are currently the three biologic drugs approved for colorectal cancer treatment, but other drugs are in development. Targeted therapies involve many different types of drugs and molecular pathways. These include:

Angiogenesis Inhibitors: Anti-angiogenesis drugs inhibit the formation of new blood vessels that supply tumors with the blood, oxygen, and nutrients vital to tumor growth. Angiogenesis inhibitors, such as the monoclonal antibody bevacizumab (Avastin), target vascular endothelial growth factor (VEGF). Cediranib (Recentin), formerly AZD2171, is a new angiogenesis inhibitor that is in Phase III clinical trials for treatment of colorectal cancer.

Tumor Growth Factor Inhibitors: Tumor growth factors, such as epidermal growth factor, stimulate cell growth. Cetixumab (Erbitux) and panitumumab (Vectibix) are the two currently approved colorectal cancer drugs that target the epidermal growth factor receptor (EGFR). Nimotuzumab (TheraCIM) is currently being studied in combination with irinotecan.

Tyrosine Kinase Inhibitors. Tyrosine kinase is an enzyme associated with EGFR that is involved with the signaling mechanisms that prompt cell growth. The EGFR/tyrosine kinase inhibitor erlotinib (Tarceva), which is approved for the treatment of pancreatic and lung cancers, is being investigated as an adjuvant treatment for metastatic colorectal cancer. Sunitinib (Sutent), which is approved for renal cell carcinoma, is another tyrosine kinase inhibitor in trials for colorectal cancer.

Reference: New York Times, Health Section ( www.health.nytimes.com), July 12, 2012