Phase I study of weekly cisplatin, vinorelbine, and concurrent thoracic radiation therapy in patients with locally advanced non-small-cell lung cancer

Background. The combination of chemotherapy and thoracic radiation therapy (TRT) is considered as a standard treatment for locally advanced non-small-cell lung cancer (NSCLC). Although the frequent interaction of anticancer agents and irradiation may produce stronger radio-sensitizing effects, the daily administration of these agents is complicated. We therefore used weekly administration of these agents, and conducted a phase I study of weekly cisplatin, vinorelbine, and concurrent TRT. The purpose of this study was to identify the maximum tolerated dose (MTD), the dose-limiting toxicity (DLT), and the recommended dose of this treatment. Methods. Patients with locally advanced NSCLC were enrolled in this study. Both cisplatin and vinorelbine were given intravenously on a weekly schedule for 6 weeks, starting on the first day of TRT, i.e., on days 1, 8, 15, 22, 29, and 36. The total dose of TRT was 60∈Gy. The dose of cisplatin was fixed at 20∈mg/m2 per week. The starting dose of vinorelbine was 15∈mg/m2 per week (dose level 1). Results. Nine patients were enrolled in this study. All three patients at dose level 1 experienced DLTs. We decreased the dose of vinorelbine to 10∈mg/m2 per week (dose level 0). Two of the six patients at dose level 0 experienced DLTs. Therefore, dose level 1 was considered as the MTD, and dose level 0 as the recommended dose. The DLTs of this treatment were esophagitis, fatigue, infection, and hyponatremia. Conclusion. The recommended dose of cisplatin is 20∈mg/m2 per week and that of vinorelbine is 10∈mg/m2 per week with standard TRT. A phase II study of this treatment is warranted. © The Japan Society of Clinical Oncology 2006.