Topotecan-docetaxel combo beneficial in heavily treated gynecologic cancer patients

NEW YORK (Reuters Health) - When given together on a weekly basis, topotecan and docetaxel appear to benefit patients with recurrent uterine, ovarian and primary peritoneal cancers who had received prior combination chemotherapy regimens, according to a study by researchers at Albert Einstein College of Medicine, Bronx, New York.

The study, reportedly the first to evaluate this drug regimen in such patients, also found that the combination of these two chemotherapy agents was well tolerated. The report of the single-center trial was published online ahead of print on April 21 by Gynecologic Oncology.

As an open-label phase 2 trial, the study did not include a control group. Nonetheless, senior author Dr. Mark H. Einstein told Reuters Health, "Typical results for overall clinical benefit in this heavily pretreated population are much worse, with generally higher toxicity."

Although recurrent gynecologic cancers tend to be difficult to treat, topotecan and taxanes, such as docetaxel, are commonly used in such situations, though not always in combination. Earlier phase 1 trials evaluated docetaxel with daily intravenous topotecan; this study was undertaken to test whether weekly dosing of these two drugs might preserve their synergy while decreasing toxicity.

The study enrolled 29 patients, with 27 treated under the protocol. Of these, 15 had recurrent epithelial ovarian cancer, 3 had primary peritoneal cancer, and 9 had recurrent uterine cancer. All had been treated previously with chemotherapy regimens, and most had two such prior treatments.

Participants received topotecan 3.5 mg/m� followed by docetaxel 30 mg/m� on day 1 and then weekly. Each cycle consisted of 3 weeks of therapy followed by a 1-week rest. Patients went through a total of 6 cycles, unless the protocol was interrupted by progressive disease, dose-limiting toxicity or death.

There were three grade 4 toxicities and 4 grade 3 toxicities during a total of 86 treatment cycles.

Of the 24 evaluable patients, 2 had a complete response, 4 had a partial response, 3 had stable disease and 15 had progressive disease. The overall response rate was therefore 25%, with 38% of patients receiving clinical benefit. The median overall survival was 18.5 months.

Three patients with platinum-resistant ovarian cancer responded to treatment. Although this was not statistically significant, it suggests "that further evaluation of this regimen in patients with platinum-resistant ovarian cancer and recurrent high-risk uterine cancers is warranted," the researchers write.

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