Aflibercept, also known as the VEGF Trap, has been co-developed by Sanofi-Aventis and Regeneron Pharmaceuticals. It is a protein that is engineered to interact with and block the actions of human vascular endothelial growth factor, or VEGF. By these actions, this drug may potentially inhibit the growth of blood vessels in tumors and increase the death rate of cancer cells. The safety and efficacy of aflibercept is currently being evaluated in multiple clinical trials, including those involving ovarian cancer patients.
Ovarian Cancer
Ovarian cancer originates in the female reproductive glands called the ovaries. Ovarian cancer is not detected by the Pap smear. The National Cancer Institute, or NCI, reports that the age-adjusted incidence rate was 12.9 per 100,000 women per year for ovarian cancer between the years 2003 and 2007. The Centers for Disease Control and Prevention, or CDC, says that deaths from ovarian cancer exceed those of any other gynecologic cancer in the United States; however, ovarian cancers account for only about 3 percent of all cancers in women. When ovarian cancer is detected early, treatment is most effective. A study in "Lancet Oncology" says that first-line chemotherapy is unsuccessful in treating epithelial ovarian cancer in 20 percent of cases, and between 40 and 50 percent of women who do respond to treatment will relapse.
Aflibercept Actions
The hormone vascular endothelial growth factor, or VEGF, stimulates the growth of new blood vessels, which are required for tumors to grow. Aflibercept blocks VEGF from interacting with its receptor and stops blood vessel growth. When this happens, tumor cells are starved for oxygen and nutrients and can no longer grow and often die. Because drugs that inhibit new vessel growth work by a different mechanism than other chemotherapeutic drugs or radiotherapy, they may enhance the therapeutic actions of conventional treatments of cancer. A review study in a 2009 issue of "Future Oncology" reports that ovarian cancers grow and metastasize in a VEGF-dependent manner and that inhibiting VEGF has proven effective in treating ovarian cancer.
Clinical Trials
A phase I and II clinical trial evaluating the efficacy and safety of aflibercept for the treatment of ovarian carcinoma is currently being conducted as of 2010, and results have not been released. A clinical trial reported at the Proceedings of the American Society of Clinical Oncology (ASCO) Annual Meeting studied the effects of aflibercept treatment alone in women with advanced ovarian cancer and found a slight tumor response. However, aflibercept did eradicate or stabilize ascites in the patients of this trial. Ascites, which is an increase in abdominal fluid, is a potentially serious complication of ovarian cancer. The review in "Future Oncology" concluded that aflibercept in combination with other chemotherapeutic drugs exhibits anti-tumor activity.
Safety
Preliminary findings of a Phase I study that is currently being conducted as of 2010 state that aflibercept does not increase docetaxel-related toxicity. The recommended dose of aflibercept in this trial was 6mg/kg. The efficacy and safety of aflibercept in combination with standard chemotherapeutic regimens is being evaluated in four Phase III trials in patients with prostate, lung, colorectal and pancreatic cancers. In general, drugs that inhibit blood vessel growth may potentially affect wound healing and increase bleeding.
Other Similar Drugs
Multiple drugs that act similar to aflibercept are being evaluated as a strategy to improve chemotherapeutic regimens. The drug bevacizumab, which has been approved by the Food and Drug Administration for the treatment of multiple cancers, also blocks VEGF activity and is often the drug of choice. The review in "Future Oncology" states that new generation drugs that block blood vessel growth may include those that block expression of VEGF so that it is never made into a protein that can act on blood vessel cells.
References
- National Cancer Institute: SEER Stat Fact Sheets: Ovary
- Centers for Disease Control and Prevention: Ovarian Cancer
- National Cancer Institute: Aflibercept
- National Cancer Institute: What You Need t Know About Ovarian Cancer
- PubMed: Collateral Damage: Toxic Effects of Targeted Antiangiogenic Therapies in Ovarian Cancer
