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Eur J Cancer. 2002 Mar;38(4):497-504.

Phase I pharmacokinetic and sequence finding study of the combination of docetaxel and methotrexate in patients with solid tumours.

Author information

1
Department of Medical Oncology, Rotterdam Cancer Institute, University Hospital Rotterdam, PO Box 5201, 3008 AE, Rotterdam, The Netherlands.

Abstract

This phase I study was performed to assess the feasibility and possible enhanced antitumour activity of the sequential administration of methotrexate (MTX) and docetaxel (D) in patients with solid tumours. Pharmacokinetic analysis was performed to investigate the pharmacokinetic interaction of the two agents. A total of 22 patients were enrolled, a total of six dose levels were investigated. MTX (days 1+15) 30, 40 and 50 mg/m(2)+D (day 2 or day 1) 75 and 85 mg/m(2) with supportive care measures. Both haematological and non-haematological toxicities were significant, preventing dose escalation above MTX 40 mg/m(2)+D 75 mg/m(2). Four partial responses were documented, three in patients with breast cancer, one in a patient with urothelial cell cancer. Pharmacokinetic data did not give an explanation for the significant toxicity as they revealed no interaction of D and MTX kinetics. Methotrexate and 7-OH MTX kinetics seemed to be independent of the administration of D and the moment of D administration appeared not to influence MTX kinetics. The sequential administration of MTX and D results in significant toxicity without any evidence of a clinical benefit.

PMID:
11872341
DOI:
10.1016/s0959-8049(01)00386-0
[Indexed for MEDLINE]

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