A phase I and pharmacokinetic study of BAY59: a novel taxane.

Abstract

PURPOSE:

To determine the maximum tolerated dose (MTD), the dose limiting toxicities (DLT) and the pharmacokinetics of BAY59, a novel taxane given as a 1-hour intravenous infusion every 3 weeks in patients with advanced refractory solid tumors.

EXPERIMENTAL DESIGN:

Initially, 15 patients with previously treated (median of 4 prior chemotherapy regimens) refractory cancers, but with normal marrow, hepatic and renal function were treated with BAY59 at doses of 15, 30, 50, 75 and 100 mg/m2 using a standard dose escalation design. Subsequently, 11 patients were treated, 5 at 90 mg/m2 and 6 who had had prior oxaliplatin at 75 mg/m2.

RESULTS:

At 75 mg/m2, grade 4 neutropenia was noted in 2/6 patients, of whom 1 had grade 4 neutropenia lasting more than 5 days (DLT). At 100 mg/m2, 2/2 patients had febrile neutropenia, with 1 fatality. At 90 mg/m2, 2/5 patients had DLTs, including grade 3 neuropathy, severe lower extremity pain, dehydration and grade 4 neutropenia. The MTD was determined to be 75 mg/m2. A cohort of 6 patients, previously exposed to oxaliplatin, were enrolled at the MTD to evaluate the incidence of neurotoxicity. While DLTs (grade 3 arthralgia, grade 4 neutropenia) were noted in 3/6 patients, there was no increase in the incidence of neurotoxicity. There were no responses. Pharmacokinetics of BAY59 was linear over the doses studied, with a median terminal half-life of 21 h.

CONCLUSIONS:

The recommended phase II dose for BAY59 is 75 mg/m2.

• Authors: N Ramnath, J Hamm, G Schwartz, S Holden, S G Eckhardt, M R Vredenburg, R J Bernacki, C Lathia, P Kanter, P J Creaven
• Journal: Oncology (Oncology) Vol. 67 Issue 2 Pg. 123-9 ( 2004) ISSN: 0030-2414 [Print] Switzerland
• PMID: 15539916 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: 2004 S. Karger AG, Basel.

Chemical References

• Antineoplastic Agents, Phytogenic
• BAY59
• Taxoids

Topics

• Adult
• Aged
• Antineoplastic Agents, Phytogenic (administration & dosage, adverse effects, pharmacokinetics)
• Drug Administration Schedule
• Female
• Half-Life
• Humans
• Male
• Middle Aged
• Neoplasms (drug therapy)
• Taxoids (administration & dosage, pharmacokinetics)
• Treatment Outcome