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Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 2/2003

01-08-2003 | Original Article

Phase I trial of fixed dose-rate gemcitabine in combination with carboplatin in chemonaive advanced non-small-cell lung cancer: a Cancer Therapeutics Research Group study

Authors: Ross A. Soo, Hong L. Lim, Ling Z. Wang, How S. Lee, Michael J. Millward, Lay T. Tok, Soo C. Lee, Manfred Lehnert, Boon C. Goh

Published in: Cancer Chemotherapy and Pharmacology | Issue 2/2003

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Abstract

Purpose

To determine the maximally tolerated dose (MTD) of gemcitabine administered at a fixed dose-rate of 10 mg/m2 per min in combination with fixed dose carboplatin, to evaluate the toxicity of this regimen and to determine the pharmacokinetics of plasma gemcitabine.

Methods

Patients with advanced stage non-small-cell lung cancer (NSCLC) received carboplatin (AUC 5) on day 1 followed by gemcitabine at a fixed dose rate of 10 mg/m2 per min in escalating durations of infusion on days 1 and 8 every 21 days. Pharmacokinetic sampling was obtained on day 1, cycle 1 of treatment.

Results

A total of 15 patients received carboplatin and gemcitabine in cohorts of three to six patients at three dose levels. The doses of gemcitabine studied were 600, 750, and 900 mg/m2. The MTD was reached at 900 mg/m2. Dose-limiting toxicities were thrombocytopenia and liver failure, and with repeated dosing neutropenia was commonly observed. The recommended phase II dose of gemcitabine was 750 mg/m2. Partial responses were observed at 600 and 750 mg/m2 of gemcitabine. Plasma gemcitabine did not reach steady state except in one patient with the durations of infusion studied. Plasma concentrations, however, were above 10 μmol/l between 20 and 90 min in all patients.

Conclusions

Gemcitabine administered as a 75-min infusion at a fixed dose rate of 10 mg/m2/min on days 1 and 8 in combination with carboplatin on day 1 every 21 days is tolerable and active in NSCLC. Pharmacokinetic studies demonstrated that the target plasma gemcitabine concentration above 10 μmol/l was achieved. Further studies are warranted to compare this regimen against standard regimens of carboplatin and gemcitabine.
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Metadata
Title
Phase I trial of fixed dose-rate gemcitabine in combination with carboplatin in chemonaive advanced non-small-cell lung cancer: a Cancer Therapeutics Research Group study
Authors
Ross A. Soo
Hong L. Lim
Ling Z. Wang
How S. Lee
Michael J. Millward
Lay T. Tok
Soo C. Lee
Manfred Lehnert
Boon C. Goh
Publication date
01-08-2003
Publisher
Springer-Verlag
Published in
Cancer Chemotherapy and Pharmacology / Issue 2/2003
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-003-0637-5

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