A drug that may help prevent recurrence of ovarian cancer by inhibiting development of new blood vessels essential to cancer growth is under study at the Medical College of Georgia.
MCG is among some 25 centers nationally enrolling patients in remission to see if the investigational drug A6 can help them stay that way, says Dr. Sharad Ghamande, MCG gynecologic oncologist and a principal investigator on the study.
In the new study, participants will give themselves daily subcutaneous injections of the drug for four weeks, followed by seven days off. The cycle can be repeated up to 11 times if the disease remains in remission and there are no significant medication side effects.
"For a tumor to grow and spread, it needs blood supply," says Dr. Ghamande. "This blood supply arises de novo. The cancer produces cytokines (growth factors) that stimulate growth of vessel buds around it in a process called angiogenesis. This particular medication targets receptors on new budding blood vessels in an attempt to down-regulate them and prevent growth. If that process is shut down, the tumor should not grow or spread."
A6 has been shown to inhibit cancer metastasis in animal studies and showed "encouraging responses" in patients with advanced ovarian cancer in Phase 1 clinical trials, according to Virgil Thompson, president and chief executive officer of Angstrom Pharmaceuticals, Inc. Daily injections of A6 also were well-tolerated by patients in the earlier study, according to the San Diego-based company.
About 24,000 new cases of ovarian cancer are diagnosed each year and about three-quarters of those new patients have advanced disease. "Ovarian cancer has no early signs and symptoms and there is not yet a screening test, such as the Pap smear for cervical cancer," Dr. Ghamande says.
Despite the advanced stage of their disease at diagnosis, many women go into clinical remission following surgery and chemotherapy. Afterward, they are followed with regular physical exams and monitoring of CA 125 levels. CA 125 is a tumor marker expressed in about 90 percent of ovarian cancer cells in patients with advanced disease. MCG is participating in a separate trial of a monoclonal antibody that targets CA 125 as a different approach to forestalling cancer recurrence.
Despite initial success, ovarian cancer often recurs within two years, with increasing CA 125 levels typically as the first sign. Five-year survival rates are about 30 percent to 35 percent for stage three disease and 5 percent to 10 percent for the more-advanced stage four.
Patients in remission today may opt for an additional year of chemotherapy, which may delay recurrence but does not always translate to a longer life, Dr. Ghamande says. Also, the side effects of chemotherapy often mean well-intended patients never complete that second year.
A6 may one day offer another option for these women. The current study explores the safety and efficacy of two different doses of the drug compared to placebo. Study participants must be in clinical remission and have a history of normal CA 125 levels that have begun to rise but still have no evidence of cancer on physical exam or computerized tomography scan. Approximately 60 patients will be enrolled nationally; MCG hopes to enroll about five.
Dr. Michael S. Macfee, chief of the MCG Section of Gynecologic Oncology, is a co-investigator on the study. For more information, call study coordinator Nora McClendon at 706-721-5557.