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Sequential topotecan and oral etoposide in recurrent ovarian carcinoma pretreated with platinum-taxane†
Results from a multicenter Phase I/II study
Version of Record online: 17 FEB 2005
Copyright © 2005 American Cancer Society
Volume 103, Issue 7, pages 1388–1396, 1 April 2005
How to Cite
Gronlund, B., Engelholm, S. A., Horvath, G., Mäenpää, J. and Ridderheim, M. (2005), Sequential topotecan and oral etoposide in recurrent ovarian carcinoma pretreated with platinum-taxane. Cancer, 103: 1388–1396. doi: 10.1002/cncr.20921
The following individuals and institutions participated in the creation of the protocol (in alphabetic order): Håkan Andersson (Department of Oncology, Division of Gynecological Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden), Karin Boman (Department of Gynecological Oncology, Norrland University Hospital, Umeå, Sverige), Svend Aage Engelholm (Department of Oncology, the Finsen Center, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark), Seija Grenman (Department of Obstetrics and Gynecology, Turku University Central Hospital, Turku, Finland), György Horvath (Department of Oncology, Division of Gynecological Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden), Johanna Mäenpää (Department of Gynecology, Division of Gynecological Oncology, Tampere University Hospital, Tampere, Finland), Ulla Puistola (Department of Gynecology, Oulu University Hospital, Oulu, Finland), Mona Ridderheim (Department of Gynecological Oncology, Lund University Hospital, Lund, Sweden), Per Rosenberg (Department of Gynecological Oncology, Linköping University Hospital, Linköping, Sverige), Tuula Salmi (Department of Obstetrics and Gynecology, Turku University Central Hospital, Turku, Finland), Andris Straumits (Department of Gynecological Oncology, Örebro University Hospital, Örebro, Sverige), and Merja Yliskoski (Department of Obstetrics and Gynecology, Kuopio University Hospital, Kuopio, Finland).
- Issue online: 18 MAR 2005
- Version of Record online: 17 FEB 2005
- Manuscript Accepted: 3 DEC 2004
- Manuscript Revised: 14 NOV 2004
- Manuscript Received: 28 JUL 2004
- SmithKline Beecham
- ovarian neoplasms;
- second-line treatment;
- topoisomerase inhibitor;
- Phase I;
The objectives of this study were to determine the maximum tolerable dose (MTD), toxicity, efficacy, and feasibility of a sequential regimen of fixed-dose topotecan (1.00 mg/m2 on Days 1–5) and increasing doses of oral etoposide (50 mg, 75 mg, and 100 mg on Days 6–12 or Days 6–19) in patients with recurrent ovarian carcinoma.
This multicenter, open-label study was planned as a Phase I–II study that included patients with epithelial ovarian carcinoma who failed or who developed recurrent disease < 12 months after the end of platinum and taxane-containing chemotherapy. Dose-limiting toxicity (DLT) was defined as follows: Grade 4 neutropenia for > 1 week, or neutropenic fever 38.5 °C for > 24 hours/sepsis, or Grade 4 thrombocytopenia for > 1 week, or thrombocytopenia with bleeding, or Grade 3–4 nonhematologic toxicity.
The MTD, as defined in the protocol, could not be settled because of unpredictable toxicity, because DLT was found at all dose levels except the starting dose level. In 28 patients (Phase I), 155 cycles were evaluable for toxicity. The main DLT was neutropenia Grade 4 for > 1 week or neutropenic fever/sepsis. Overall, neutropenia Grade 4 that lasted > 1 week and sepsis were noticed in 3% and 2% of cycles, respectively. Because no MTD was reached, the planned Phase II trial was not initiated. However, the patients from Phase I were followed until they developed progressive disease and, among them, 9 patients (32%) obtained an objective response (according to Response Evaluation Criteria in Solid Tumors (RECIST) or CA125 response criteria).
Combined topotecan and oral etoposide was inappropriate in patients with recurrent ovarian carcinoma because of unpredictable hematologic toxicity. However, the high objective response rate highlighted the potential additive effect of topoisomerase I and II inhibitors. Cancer 2005. © 2005 American Cancer Society.