TY - JOUR
T1 - High-dose topotecan, melphalan, and cyclophosphamide (TMC) with stem cell support
T2 - A new regimen for the treatment of advanced ovarian cancer
AU - Donato, Michele L.
AU - Gershenson, David M.
AU - Wharton, James T.
AU - Ippoliti, Cindy M.
AU - Aleman, Ana S.
AU - Bodurka-Bevers, Diane
AU - Bevers, Michael W.
AU - Burke, Thomas W.
AU - Levenback, Charles F.
AU - Wolf, Judith K.
AU - Freedman, Ralph S.
AU - Bast, Robert C.
AU - Gajewski, James L.
AU - Champlin, Richard E.
N1 - Funding Information:
1Supported by a grant from SmithKline Beecham.
PY - 2001
Y1 - 2001
N2 - Objective. The goal of this study was to determine the optimal dose of topotecan when used in combination with high-dose melphalan and cyclophosphamide (TMC), and to assess the toxicity and efficacy of the regimen in patients with advanced ovarian cancer. Methods. Fifty-three patients with persistent or recurrent ovarian cancer were treated. Disease status at study entry included: platinum-sensitive recurrent disease (15 patients), platinum-resistant or refractory recurrent disease (15 patients), positive second-look surgery (16 patients), failure to achieve a primary clinical complete response (CR) (7 patients). Following stem cell mobilization and collection, patients were given cyclophosphamide 1 g/m2/day on Days -6, -5, -4; melphalan 70 mg/m2/day on Days -3, -2; and topotecan at escalating doses from 1.25 to 4.0 mg/m2/day on Days -6 to -2. Peripheral blood stem cells were infused on Day 0. Results. The optimal topotecan dose selected for future trials was 4.0 mg/m2/day × 5 days. The regimen had acceptable toxicity with no regimen-related death. Toxicity (Bearman toxicity criteria) was limited mostly to grade 1-2 mucositis and diarrhea. The overall response rate of patients with measurable or evaluable disease was 93%. Median survival has not yet been reached, but with a median follow up of 18 months (range: 11-37) 77% of patients are alive. Conclusion. With a topotecan dose of 4.0 mg/m2/day × 5 days, the TMC regimen has acceptable toxicity and produces high response rates. In the setting of ovarian cancer, high-dose chemotherapy should be administered only as part of well-designed clinical trials. TMC should be considered a potential regimen for future randomized trials in patients with advanced ovarian cancer.
AB - Objective. The goal of this study was to determine the optimal dose of topotecan when used in combination with high-dose melphalan and cyclophosphamide (TMC), and to assess the toxicity and efficacy of the regimen in patients with advanced ovarian cancer. Methods. Fifty-three patients with persistent or recurrent ovarian cancer were treated. Disease status at study entry included: platinum-sensitive recurrent disease (15 patients), platinum-resistant or refractory recurrent disease (15 patients), positive second-look surgery (16 patients), failure to achieve a primary clinical complete response (CR) (7 patients). Following stem cell mobilization and collection, patients were given cyclophosphamide 1 g/m2/day on Days -6, -5, -4; melphalan 70 mg/m2/day on Days -3, -2; and topotecan at escalating doses from 1.25 to 4.0 mg/m2/day on Days -6 to -2. Peripheral blood stem cells were infused on Day 0. Results. The optimal topotecan dose selected for future trials was 4.0 mg/m2/day × 5 days. The regimen had acceptable toxicity with no regimen-related death. Toxicity (Bearman toxicity criteria) was limited mostly to grade 1-2 mucositis and diarrhea. The overall response rate of patients with measurable or evaluable disease was 93%. Median survival has not yet been reached, but with a median follow up of 18 months (range: 11-37) 77% of patients are alive. Conclusion. With a topotecan dose of 4.0 mg/m2/day × 5 days, the TMC regimen has acceptable toxicity and produces high response rates. In the setting of ovarian cancer, high-dose chemotherapy should be administered only as part of well-designed clinical trials. TMC should be considered a potential regimen for future randomized trials in patients with advanced ovarian cancer.
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U2 - 10.1006/gyno.2001.6326
DO - 10.1006/gyno.2001.6326
M3 - Article
C2 - 11520135
AN - SCOPUS:17944374801
SN - 0090-8258
VL - 82
SP - 420
EP - 426
JO - Gynecologic oncology
JF - Gynecologic oncology
IS - 3
ER -