A Phase I Study of Carboplatin and Docetaxel for Advanced Non-small Cell Lung Cancer Using the Continual Reassessment Method

• Published in: Japanese journal of clinical oncology 2002-12, Vol.32 (12), p.512-516
• Main Authors: Kasahara, Kazuo, Myo, Saori, Iwasa, Kei-ichi, Kimura, Hideharu, Shirasaki, Hiroki, Yasuda, Utako, Shibata, Kazuhiko, Shintani, Hiromoto, Nishi, Kohichi, Fujimura, Masaki, Nakao, Shinji
• Format: Article
• Language: English
• Subjects: Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Carboplatin - administration & dosage; Carboplatin - adverse effects; Carcinoma, Non-Small-Cell Lung - drug therapy; Docetaxel; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Infusions, Intravenous; Key words: docetaxel – carboplatin – non-small cell lung cancer – continual reassessment method; Lung Neoplasms - drug therapy; Maximum Tolerated Dose; Middle Aged; Neutropenia - chemically induced; Paclitaxel - administration & dosage; Paclitaxel - adverse effects; Paclitaxel - analogs & derivatives; Taxoids; Thrombocytopenia - chemically induced
• ISSN: 0368-2811; 1465-3621; 1465-3621
• DOI: 10.1093/jjco/hyf112

Purpose: This phase I study was designed to determine the maximum tolerated dose of carboplatin combined with a fixed dose of docetaxel (60 mg/m2) 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/m2 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/m2 of docetaxel and carboplatin with a tAUC of 5.5.