A Weekly Combination of Topotecan & Docetaxel Produces Clinical Benefit In Heavily Pretreated Ovarian Cancer Patients

Recurrent and metastatic endometrial and ovarian cancers can be notoriously difficult to treat. … Physicians at the Albert Einstein College of Medicine of Yeshiva University showed that a combination of two chemotherapy drugs not only produced clinical benefit for such patients but were also well tolerated.  The results of this phase II study were published online in Gynecologic Oncology on March 21st. …[T]he researchers concluded that the combination of weekly topotecan and docetaxel has clinical benefit and is well tolerated in this heavily treated epithelial ovarian and uterine cancer patient population.  The researchers also noted that patients with platinum-resistant tumors had clinical benefit and should be considered for further study with this regimen. …

Recurrent and metastatic endometrial and ovarian cancers can be notoriously difficult to treat.  Both diseases are capable of  spreading to other organs and developing resistance to chemotherapy.  Typically, under this scenario, the patients have been heavily treated with chemotherapy and may not be able to endure additional treatment. Physicians at the Albert Einstein College of Medicine of Yeshiva University showed that a combination of two chemotherapy drugs not only produced clinical benefit for such patients but were also well tolerated.  The results of this phase II clinical study were published online in Gynecologic Oncology on March 21st.

Mark H. Einstein, M.D., M.S., Associate Professor of Obstetrics & Gynecology and Women's Health, Albert Einstein College of Medicine of Yeshiva University

Mark H. Einstein, M.D., M.S., Associate Professor of Obstetrics & Gynecology and Women's Health, Albert Einstein College of Medicine of Yeshiva University

“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.”Under the trial protocol, eligible patients with recurrent epithelial ovarian or uterine cancers were treated with weekly topotecan 3.5 mg/m(2) and docetaxel 30 mg/m(2) for 3 consecutive weeks. Cycles were repeated every 4 weeks for 6 cycles or until evidence of disease progression or unacceptable toxicity. Patient response was assessed under Response Evaluation Criteria In Solid Tumors (RECIST) or, when appropriate, Rustin’s Criteria.  The majority of patients had received 2 prior chemotherapy regimens (9 pts had received 1 previous regimen, 16 pts. had received 2, 1 pt. had received 3, and 1 pt. had received 4).  Of the twenty-seven patients registered, 24 were evaluable for response.  The results of the trial are set forth below.

  • 86 cycles of chemotherapy were administered.
  • There were three grade 4 (all neutropenia) and ten grade 3 toxicities.Six of the grade 3 toxicities were unrelated to treatment.
  • There were 8 dose delays and 4 dose reductions.
  • The overall response rate was 25%  (8% CR, 17% PR).
  • The clinical benefit rate was 38% (8% CR+17% PR+13% SD).
  • The median duration of response was 8.5 months (range 3-19 months).
  • The median overall survival was 18.5 months (range 1.8-50.7 months.

Based upon the foregoing results, the researchers concluded that the combination of weekly topotecan and docetaxel has clinical benefit and is well tolerated in this heavily treated epithelial ovarian and uterine cancer patient population.  The researchers also noted that patients with platinumresistant tumors had clinical benefit and should be considered for further study with this regimen.Compared with previous clinical trials, an unusually high proportion of these women had been heavily pretreated with chemotherapy─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 II studies that evaluated the drugs on an individual basis.  Finally, there were few and relatively mild side effects from the drug combination compared with toxicities observed in similar studies.

The effectiveness and safety outcomes of the trial are “promising enough to justify a larger clinical study of this drug combination for women with recurrent gynecologic cancers,” Dr. Einstein said.

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 trial costs.

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