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Phase I and Pharmacologic Study of Docetaxel and Irinotecan in Advanced Non–Small-Cell Lung Cancer

From the Departments of Internal Medicine, Osaka Prefectural Habikino Hospital and Kinki University School of Medicine; Department of Respiratory Disease, Osaka City General Hospital; 1st Department of Internal Medicine, Osaka City University School of Medicine, Osaka; Department of Respiratory Disease, Aichi Cancer Center, and 1st Department of Internal Medicine, Nagoya University, School of Medicine, Aichi; and The Tokyo Cooperative Oncology Group, Tokyo, Japan.

Address reprint requests to Noriyuki Masuda, MD, PhD, Department of Internal Medicine, Osaka Prefectural Habikino Hospital, 3–7-1 Habikino, Habikino Osaka 583-8588, Japan.

PURPOSE: We conducted a phase I trial of docetaxel, a new antimicrotubule agent, combined with irinotecan (CPT-11), a topoisomerase I inhibitor. The aim was to determine the maximum-tolerated dose (MTD) of docetaxel combined with CPT-11, as well as the dose-limiting toxicities (DLTs) of this combination in advanced non–small-cell lung cancer (NSCLC) patients.

PATIENTS AND METHODS: Thirty-two patients with stage IIIB or IV NSCLC were treated at 4-week intervals with docetaxel (60 minutes, day 2) plus CPT-11 (90 minutes, days 1, 8, and 15). The starting doses of docetaxel/CPT-11 were 30/40 mg/m², and doses were escalated in 10-mg/m² increments until the MTD was reached.

RESULTS: The MTD of docetaxel/CPT-11 was 50/60 mg/m² (level 5A), or 60/50 mg/m² (level 5B). Neutropenia and diarrhea were the DLTs. CPT-11 did not affect the pharmacokinetics of docetaxel. There were 11 (37%) partial responses among 30 patients. The median survival time was 48 weeks, and the 1-year survival rate was 44.9%.

CONCLUSION: The combination of docetaxel and CPT-11 seems to be active against NSCLC, with acceptable toxicity. The recommended dose for phase II studies is 50 mg/m² of CPT-11 (days 1, 8, and 15) and 50 mg/m² of docetaxel (day 2) administered every 28 days.

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