High-dose topotecan, melphalan, and cyclophosphamide (TMC) with stem cell support: A new regimen for the treatment of advanced ovarian cancer

Michele L. Donato, David M. Gershenson, James T. Wharton, Cindy M. Ippoliti, Ana S. Aleman, Diane Bodurka-Bevers, Michael W. Bevers, Thomas W. Burke, Charles F. Levenback, Judith K. Wolf, Ralph S. Freedman, Robert C. Bast, James L. Gajewski, Richard E. Champlin

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)420-426
Number of pages7
JournalGynecologic Oncology
Volume82
Issue number3
DOIs
StatePublished - 2001
Externally publishedYes

Fingerprint

Topotecan
Melphalan
Ovarian Neoplasms
Cyclophosphamide
Stem Cells
Therapeutics
Platinum
Second-Look Surgery
Hematopoietic Stem Cell Mobilization
Mucositis
Diarrhea
Clinical Trials

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Oncology

Cite this

Donato, M. L., Gershenson, D. M., Wharton, J. T., Ippoliti, C. M., Aleman, A. S., Bodurka-Bevers, D., ... Champlin, R. E. (2001). High-dose topotecan, melphalan, and cyclophosphamide (TMC) with stem cell support: A new regimen for the treatment of advanced ovarian cancer. Gynecologic Oncology, 82(3), 420-426. https://doi.org/10.1006/gyno.2001.6326

High-dose topotecan, melphalan, and cyclophosphamide (TMC) with stem cell support : A new regimen for the treatment of advanced ovarian cancer. / Donato, Michele L.; Gershenson, David M.; Wharton, James T.; Ippoliti, Cindy M.; Aleman, Ana S.; Bodurka-Bevers, Diane; Bevers, Michael W.; Burke, Thomas W.; Levenback, Charles F.; Wolf, Judith K.; Freedman, Ralph S.; Bast, Robert C.; Gajewski, James L.; Champlin, Richard E.

In: Gynecologic Oncology, Vol. 82, No. 3, 2001, p. 420-426.

Research output: Contribution to journalArticle

Donato, ML, Gershenson, DM, Wharton, JT, Ippoliti, CM, Aleman, AS, Bodurka-Bevers, D, Bevers, MW, Burke, TW, Levenback, CF, Wolf, JK, Freedman, RS, Bast, RC, Gajewski, JL & Champlin, RE 2001, 'High-dose topotecan, melphalan, and cyclophosphamide (TMC) with stem cell support: A new regimen for the treatment of advanced ovarian cancer', Gynecologic Oncology, vol. 82, no. 3, pp. 420-426. https://doi.org/10.1006/gyno.2001.6326
Donato, Michele L. ; Gershenson, David M. ; Wharton, James T. ; Ippoliti, Cindy M. ; Aleman, Ana S. ; Bodurka-Bevers, Diane ; Bevers, Michael W. ; Burke, Thomas W. ; Levenback, Charles F. ; Wolf, Judith K. ; Freedman, Ralph S. ; Bast, Robert C. ; Gajewski, James L. ; Champlin, Richard E. / High-dose topotecan, melphalan, and cyclophosphamide (TMC) with stem cell support : A new regimen for the treatment of advanced ovarian cancer. In: Gynecologic Oncology. 2001 ; Vol. 82, No. 3. pp. 420-426.
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abstract = "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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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.

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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.

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