Phase I study of a carboplatin-cisplatin-etoposide combination chemotherapy in advanced non-small-cell lung cancer.

Cisplatin (CDDP)-containing chemotherapy has become the mainstay of clinical trials in unresectable non-small-cell lung cancer (NSCLC), but the role of chemotherapy in the routine management of NSCLC remains controversial. We conducted a phase I study with the combination carboplatin (CBDCA), CDDP, and etoposide (Etop) in unresectable NSCLC. CBDCA, at a starting dose of 80 mg/m(2) on day 1, was combined with a fixed dose of CDDP (80 mg/m(2), day 1) and Etop (80 mg/m(2), days 1-3). Escalation was performed after four patients entered at each dose level. If no World Health Organization (WHO) grade 4 toxicity developed after the first cycle in more than half of the patients or WHO grade 3/4 toxicity in more than two thirds, the dose was escalated. The maximum tolerated dose was established at 300 mg/m(2) for CBDCA. Thrombocytopenia and leukopenia were the dose-limiting toxicities. No grade 3/4 nonhematologic toxicities were seen. The recommended dose of CBDCA to be combined with CDDP (80 mg/m(2), day 1) and Etop (80 mg/m(2), days 1-3) is 280 mg/m(2). This trial suggests that our combination chemotherapy may be effective in patients with advanced NSCLC. A multicenter phase II study based on these findings is now under way.