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

Abstract

BACKGROUND:

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.

PATIENTS AND METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

• Authors: 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
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 15 Issue 8 Pg. 1284-94 (Aug 2004) ISSN: 0923-7534 [Print] England
• PMID: 15277271 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Controlled Clinical Trial, Journal Article)
• Copyright: Copyright 2004 European Society for Medical Oncology

Chemical References

• 20-O-(Nalpha-(4-(3-O-methylfucopyranosyloxy)phenylaminothiocarbonyl)histidylvalyl)camptothecin
• Dipeptides
• Camptothecin

Topics

• Camptothecin (administration & dosage, adverse effects, analogs & derivatives, pharmacokinetics)
• Dipeptides (administration & dosage, adverse effects, pharmacokinetics)
• Drug Administration Schedule
• Female
• Humans
• Infusions, Intravenous
• Male
• Maximum Tolerated Dose
• Middle Aged
• Neoplasms (drug therapy)