Phase I and pharmacokinetic study of carboplatin and paclitaxel with a biweekly schedule in patients with advanced non-small-cell lung cancer.
OBJECTIVE
A phase I study was conducted to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of carboplatin in combination with paclitaxel using a biweekly schedule in patients with advanced non-small-cell lung cancer (NSCLC).


METHODS
The pharmacokinetics of paclitaxel were determined preliminarily in some patients. The criteria for eligibility for study entry included histologically and/or cytologically confirmed NSCLC (stage IIIb or IV), no prior treatment, and measurable disease. Paclitaxel was given in combination with a fixed dose of carboplatin at an area under the concentration-time curve (AUC) of 3 mg/ml x min, every 2 weeks. The starting dose of paclitaxel was 100 mg/m(2), and the dose was increased in increments of 20 mg/m(2). Three to six patients were allocated to each dose level.


RESULTS
A total of 19 patients (11 male and 8 female) with a median age of 61 years (range 43-74 years) and a median ECOG performance status of 0 (range 0-1) were enrolled. The MTD of paclitaxel proved to be 160 mg/m(2), and the DLT was neutropenia, which improved well following treatment with G-CSF. Gastrointestinal toxicity was well tolerated. Of 17 patients who received four cycles or more, 7 (41%; 95% confidence interval 18.4-67.1%) responded to this combination therapy. The pharmacokinetics of paclitaxel did not differ from published data.


CONCLUSIONS
The recommended dose for phase II study is paclitaxel 140 mg/m(2) with a carboplatin AUC of 3 mg/ml.min. This biweekly regimen is highly effective and acceptable, and the present data indicate that the regimen may be suitable for use on an outpatient basis.
First Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, 830-0011 Kurume, Japan. ichiki@med.kurume-u.ac.jp
M
M
Ichiki
R
R
Gohara
R
R
Fujiki
S
S
Hoashi
T
T
Rikimaru
H
H
Aizawa
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D019540:Area Under Curve; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D004334:Drug Administration Schedule; D005260:Female; D006207:Half-Life; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage
D016190:Carboplatin; D017239:Paclitaxel