Phase I trial of escalating doses of topotecan in combination with a fixed dose of pegylated liposomal doxorubicin in women with müllerian malignancies (original) (raw)

Gynecologic Oncology, 2004

Abstract

Background. Topotecan and pegylated liposomal doxorubicin (Doxil) interact with topoisomerase I and II (topo I and II), respectively, with schedule dependent, and potentially synergistic cytotoxicity.Objectives. Define dose-limiting toxicity (DLT) and determine the maximum tolerated dose (MTD) of topotecan delivered by 72-h infusion administered immediately after Doxil delivered at a fixed dose (30 mg/m2) in a cohort of women with recurrent müllerian malignancies.Methods. Topotecan dose was escalated from 0.5 mg/m2/day for 3 days in 0.2 mg/m2/day increments with treatment repeated every 21 days. Eligibility criteria required ECOG ≤2 and no more than four prior lines of chemotherapy. No dose reductions were allowed in the first two cycles to allow evaluation of cutaneous toxicity.Results. Between November 2000 and August 2002, 18 patients were enrolled. Median age 59 (40–71) years. Patients received a median 1 (1–6) cycles of chemotherapy, with 39 cycles of treatment delivered at DL 1. All patients were evaluable for toxicity and 12 for response. At dose level 2, dose-limiting toxicity consisted of nausea and vomiting, mucositis, cutaneous toxicity, and neutropenia. There was no clinically significant cardiac toxicity. There were no radiologically confirmed partial responses.Conclusions. Doxil 30 mg/m2 and topotecan 0.5 mg/m2/day by 72-h infusion (total dose 1.5 mg/m2), although a rational combination of cytotoxic therapies, have limited clinical activity.

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