For Recurrent Ovarian and Uterine Cancers: A Weekly Chemotherapy Regimen
April 29, 2009 — A weekly regimen of topotecan and docetaxel for recurrent uterine and ovarian cancers in heavily pretreated women might provide clinicians with another option in this difficult setting, according to researchers at Albert Einstein College of Medicine of Yeshiva University in New York City.
In a phase 2 study, the overall response rate with the combination was 25% (95% confidence interval, 7.7%–42.3%); 8% had a complete response and 17% had a partial response. The response rate was within the range of results from previous studies of weekly topotecan monotherapy, wrote the authors of the study, which was published online March 21 in Gynecologic Oncology.
However, as the authors pointed out in emphasizing their positive results, "our study included more heavily pretreated subjects than most previously reported studies."
The study's 24 evaluable participants had a median survival of 18.5 months, which is higher than in previous phase 2 studies that evaluated these drugs as monotherapies, wrote the authors, led by senior author Mark H. Einstein, MD, Associate Professor of Obstetrics and Gynecology and Women's Health at Albert Einstein College of Medicine.
The study is the first to evaluate this combination in this setting.
The combination of topotecan and docetaxel has previously been evaluated in recurrent ovarian and uterine cancers-but as a daily regimen. However, there was dose-limiting myelosuppression (neutropenia and/or thrombocytopenia) with the daily treatments, according to the authors.
In the current study, of the 86 cycles completed by the patients, there were 9 clinically relevant toxicities (10%). Dose reductions and treatment delays were "infrequent," the authors noted. "The safety profile of this regimen is acceptable in a heavily pretreated population," wrote the authors.
The strategy of using the regimen weekly seems to have paid off in terms of toxicities, suggested Dr Einstein, noting that toxicities are an issue in pretreated patients, who have often developed chemotherapy resistance.
"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 anticancer drugs," said Dr Einstein in a press statement.
Overall, the results were encouraging to the investigators, who said further evaluation is warranted.
Topotecan and docetaxel are commonly used in recurrent ovarian cancer, and there is evidence of "an incomplete cross-resistance between these 2 agents," the authors noted. Because the antitumor activity of topotecan and docetaxel might not be cross-resistant, the combination has potential in this setting. Furthermore, in vitro data have shown that this combination might have synergistic effects on tumor death, the authors added.
In the current phase 2 evaluation of this doublet regimen, the women had either recurrent uterine, epithelial ovarian, fallopian, or primary peritoneal cancer. Patients were treated with topotecan 3.5 mg/m2 followed by docetaxel 30 mg/m2 on day 1, and weekly thereafter. Each cycle consisted of once-weekly therapy for 3 weeks followed by a 1-week rest, for a total of 6 cycles.
All 27 enrolled patients had previously received combination chemotherapy regimens: 9 had received 1 previous regimen, 16 had received 2, 1 had received 3, and 1 had received 4.
The response to treatment of targeted lesions was evaluated with computed tomography scans before the start of therapy, after 3 cycles, and at the end of therapy. Response was measured using standard RECIST (response evaluation criteria in solid tumors) and, where appropriate, modified Rustin's criteria.
Of the 24 evaluable patients, 2 patients had a complete response, 4 had a partial response, 3 had stable disease, and 15 had progressive disease. The median time to best response was 2.5 months. The median duration of response was 8.5 months.
In terms of adverse events, there were 3 grade 4 toxicities—all related to severe neutropenia. Two of these patients required granulocyte colony-stimulating factor support for neutropenia.
There were also 10 grade 3 toxicities, but 6 were not treatment-related (such as back pain from metastases). Two of the grade 3 toxicities were thrombocytopenia. There were 8 dose delays and 4 dose reductions.
Source: Medscape Medical News
