April 21, 2009 — (BRONX, NY) — Recurrent and metastatic endometrial and ovarian cancers can be notoriously difficult to treat: They have spread to other organs and typically have developed resistance to chemotherapy; and patients already heavily treated with chemotherapy may not be able to endure more chemo. Now, physicians at Albert Einstein College of Medicine of Yeshiva University have shown that a combination of two chemotherapy drugs not only produced clinical benefit for such patients but were also well tolerated. The findings are published online in the journal Gynecologic Oncology.
Mark Einstein, M.D., M.S. "Women with recurrent gynecologic cancers have often had multiple rounds of chemotherapy, which can cause tumor cells to develop resistance to these drugs," says Mark H. Einstein, M.D., M.S., associate professor of obstetrics & gynecology and women's health at Einstein, who headed the study. "This resistance can make it difficult for doctors to devise a treatment protocol that will impact the cancers while avoiding the often-severe side effects that certain chemotherapy drugs can cause, particularly when patients have already been heavily pretreated with other anti-cancer drugs."
In previous clinical studies, the chemotherapy drugs topotecan and docetaxel showed effectiveness when used separately against recurrent gynecologic cancers. The phase 2 trial conducted by Dr. Einstein and his colleagues — the first to evaluate the combination of the drugs for this purpose — involved 24 women with recurrent uterine, ovarian, fallopian or peritoneal cancers. The women were given the topotecan-docetaxel combination on Day 1 of the trial and then weekly for three weeks; after a one-week rest, the women received another three-week treatment cycle, ultimately undergoing six such treatment cycles.
Compared with previous clinical trials, an unusually high proportion of these women had been heavily pretreated with chemotherapyâ”€yet nearly 40 percent of them experienced clinical benefit. In addition, the overall survival with the drug combination (median survival of 18.5 months) was higher than in previous phase 2 studies that evaluated the drugs when used singly. Finally, there were few and relatively mild side effects from the drug combination compared with toxicities observed in similar studies.
The trial's effectiveness and safety outcomes are "promising enough to justify a larger clinical study of this drug combination for women with recurrent gynecologic cancers," Dr. Einstein says.
Other researchers at Einstein involved in the trial were Divya Gupta, M.D., Ricky L. Owers, M.D., Mimi Kim, Sc.D., Dennis Yi-Shin Kuo, M.D., Gloria S. Huang, M.D., Shohreh Shahabi, M.D., and Gary L. Goldberg, M.D.
Dr. Einstein's research was funded, in part, by investigator-initiated grants from Sanofi-Aventis and GlaxoSmithKline Oncology for research-related costs of this trial.