A phase I study of carboplatin plus oral topotecan in advanced malignancies

Abstract

2137 Background: Topotecan given by continuous infusion (CIV) causes less myelosuppression (M) than bolus topotecan; when given orally bid, it may mimic CIV. Tolerance of “topotecan per os” (TPO) with carboplatin (C) was studied in a dose escalation schema. Methods: Patients (pts) with advanced malignancy, PS 0–1, <4 prior regimens, and adequate organ function were eligible. All pts received prior therapy. C AUC 4 D1 and TPO 0.4 mg/m2 or 0.5 mg/m2 bid x 21 days (d) were given every 28d. TPO dosing was interrupted for ANC < 1000 or plts ≤ 75K. Results: The first 7 pts were treated at dose level 1 (0.4mg/m2) and 3 at dose level 2 (0.5mg/m2). Only 11/25 cycles of TPO were given for a full 21d. Reasons for not completing TPO cycles - 7 thrombocytopenia (T), 3 infection (I), 2 progressive disease (PD), 1 adverse event (AE), 1 patient decision. Of 11 complete TPO cycles, 5 subsequent cycles were delayed (3 T, 1 neutropenia (N), 1 I). M was the most serious toxicity, with 3 developing G4 N, 2 febrile neutropenia (FN), and 3 G4 T. In contrast to our prior reports of TPO with either cisplatin or doxil (ASCO 2001 abstract # 2075, mainly ovarian pts), GI toxicity was not dose-limiting (no G3/4 vomiting (V) diarrhea (D)). One partial response (PR) for 22 weeks (wks) and 1 stable disease (SD) for 10 wks were noted (Table 1). Conclusion: C plus TPO had M as the dose-limiting toxicity. In contrast to other TPO regimens, GI toxicity was less severe. We recommend TPO 14d dosing (rather than 21d) when given in combination. Supported by GlaxoSmithKline, NCI core grant # P30 CA16087 Table 1 CTC v 2.0 Common Toxicity Criteria Version 2.0 (or CTC v 2.0) Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb GlaxoSmithKline