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A new therapeutical approach: Topotecan plus gemcitabine in the treatment of patients with relapsed ovarian cancer after failure of first‐line chemotherapy with paclitaxel and platinum
Author(s) -
Sehouli Jalid,
Stengel Dirk,
Oskay Gülten,
Blohmer Jens,
Kaubitzsch Sabine,
Lichtenegger Werner
Publication year - 2003
Publication title -
journal of obstetrics and gynaecology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.597
H-Index - 50
eISSN - 1447-0756
pISSN - 1341-8076
DOI - 10.1046/j.1341-8076.2003.00087.x
Subject(s) - medicine , topotecan , gemcitabine , paclitaxel , oncology , chemotherapy , ovarian cancer , first line treatment , cancer
Aim: Topotecan and gemcitabine have demonstrated mono‐activity against recurrent ovarian cancer. Both drugs affect DNA replication; in addition, topotecan inhibits DNA repair. Based on the efficacy profiles and different mechanisms of action, a phase‐I study was conducted to determine the maximum tolerated dose (MTD) of topotecan (day 1–5) and the dose‐limiting toxicities (DLT) in combination with gemcitabine (day 1 + 8) every 21 days. Methods: Three to six patients were treated per dose‐level. Patients with ovarian cancer who had failed a platinum and paclitaxel‐containing therapy were enrolled. No individual dose escalation or use of cytokines were allowed. Results: Twenty‐three patients were recruited. Fifty percent of all patients were pretreated with at least two platinum‐containing therapies. Eighty courses were assessable for toxicity. The MTD was reached at a dosage of 0.75 mg/m 2 topotecan in combination with 800/600 mg/m 2 gemcitabine. Thrombocytopenia and leucopenia were the major DLTs. The dose for phase‐II trials is 0.50 mg/m 2 topotecan given with 800/600 mg/m 2 gemcitabine. In this dose‐level only one related non‐haematological adverse event> grade 2 was observed (grade 3 mycotic stomatitis) and one grade 4 thrombocytopenia occurred. Responses were observed in six patients and stable disease in four out of 12 assessable patients. Median survival time was 15.3 (95% CI: 13.21–28.64) months. Conclusion: The results demonstrate feasibility and the tolerability of topotecan in combination with gemcitabine in recurrent ovarian cancer patients. Based on these results a phase‐II study was conducted to evaluate the efficacy of this new combination.