A phase I study of carboplatin and docetaxel for advanced non-small cell lung cancer using the continual reassessment method.
OBJECTIVE
This phase I study was designed to determine the maximum tolerated dose of carboplatin combined with a fixed dose of docetaxel (60 mg/m(2)) and the safety and efficacy of this combination chemotherapy in unresectable non-small cell lung cancer.


METHODS
Patients received a 60 min intravenous infusion of docetaxel followed by a 90 min infusion of carboplatin with dose escalation using the continual reassessment method. The starting dose of carboplatin was targeted to an area under the plasma concentration curve of 3 using Calvert's equation and dose escalation was based on course 1 toxicities.


RESULTS
From January 1999 to February 2000, 16 patients entered this trial. The major dose-limiting toxicity was neutropenia. Thrombocytopenia was rare and major non-hematological toxicities included fever that was not associated with neutropenia and grade 2 nausea and vomiting. Objective responses were seen in five patients (response rate 31.3%).


CONCLUSIONS
Based on this phase I clinical trial, the maximum tolerated dose of carboplatin combined with 60 mg/m(2) of docetaxel was a target area under the plasma concentration curve (tAUC) of 6 and the recommended tAUC for further trials is 5.5. This combination appeared to be effective for non-small cell lung cancer. A phase II clinical trial is recommended using 60 mg/m(2) of docetaxel and carboplatin with a tAUC of 5.5.
Kasahara
Kazuo
K
Respiratory Medicine, School of Medicine, Kanazawa University, Japan. kasa1237@med3.m.kanazawa-u.ac.jp
Myo
Saori
S
Iwasa
Kei-ichi
K
Kimura
Hideharu
H
Shirasaki
Hiroki
H
Yasuda
Utako
U
Shibata
Kazuhiko
K
Shintani
Hiromoto
H
Nishi
Kohichi
K
Fujimura
Masaki
M
Nakao
Shinji
S
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy*; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D043823:Taxoids; D013921:Thrombocytopenia / Q000139:chemically induced
D043823:Taxoids; D000077143:Docetaxel; D016190:Carboplatin; D017239:Paclitaxel