A phase I clinical and pharmacokinetic study of the camptothecin glycoconjugate, BAY 38-3441, as a daily infusion in patients with advanced solid tumors.

K Mross, H Richly, N Schleucher, S Korfee, M Tewes, M E Scheulen, S Seeber, T Beinert, M Schweigert, U Sauer, C Unger, D Behringer, E Brendel, C G Haase, D Voliotis, D Strumberg

Department of Medical Oncology, Tumor Biology Center at the University of Freiburg, Berlin, Germany.

Annals of oncology : official journal of the European Society for Medical Oncology / ESMO 2004 Aug

filter terms:

The aim of this study was to define the maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and pharmacokinetics of the camptothecin glycoconjugate BAY 38-3441, administered as an infusion for 30 min on two separate schedules every 3 weeks. A total of 81 patients with advanced solid tumors were treated with BAY 38-3441 either at doses of 20, 40, 67, 100, 140, 210, 315, 470 and 600 mg/m2/day for 1 day every 3 weeks (single-dose schedule), or at doses of 126, 189, 246, 320 and 416 mg/m2/day once daily for three consecutive days every 3 weeks (3-day schedule). Plasma sampling was performed to characterize the pharmacokinetics of BAY 38-3441 and camptothecin with these schedules. DLTs included renal toxicity, granulocytopenia and thrombocytopenia on the single-day schedule at doses > or = 470 mg/m2/day, and diarrhea and thrombocytopenia on the 3-day schedule at doses > or = 320 mg/m2/day. Other non-DLTs were gastrointestinal, dermatological and hematological. Pharmacokinetics of BAY 38-3441 and camptothecin appear to be dose-dependent, but not linear. Renal toxicity was dose-limiting for BAY 38-3441 using 30-min infusions on the single-dose schedule. Dose escalation to 470 mg/m2/day is feasible using a 2-h infusion. However, because of the superior safety profile, we recommend the 3-day schedule for BAY 38-3441 at a dose of 320 mg/m2/day as 30-min infusions for further phase II studies. Copyright 2004 European Society for Medical Oncology

Citation

K Mross, H Richly, N Schleucher, S Korfee, M Tewes, M E Scheulen, S Seeber, T Beinert, M Schweigert, U Sauer, C Unger, D Behringer, E Brendel, C G Haase, D Voliotis, D Strumberg. A phase I clinical and pharmacokinetic study of the camptothecin glycoconjugate, BAY 38-3441, as a daily infusion in patients with advanced solid tumors. Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. 2004 Aug;15(8):1284-94