Phase I/II study of escalating doses of vinorelbine in combination with oxaliplatin in patients with advanced non-small-cell lung cancer.

Abstract

Oxaliplatin is a platinum compound active in non-small-cell lung cancer (NSCLC) patients, and vinorelbine (VNB) is an active reference agent. This phase I/II study was performed to determine the dose-limiting toxicity (DLT), the maximum-tolerated dose (MTD), and the recommended dose (RD) of a VNB/oxaliplatin combination given to previously untreated patients with advanced NSCLC. Oxaliplatin was given at the fixed dose of 130 mg/m2 (2-hour intravenous [IV] infusion) on day 1. VNB was administered on days 1 and 8 (10-minute IV infusion), with doses starting at 22 mg/m2/d and escalated by 2 mg/m2 increments until MTD. Treatment was repeated every 3 weeks. No special hydration measures or prophylactic granulocyte colony-stimulating factors were used. Twenty-seven patients (20 men, 7 women) received 110 cycles total at six different VNB dose levels. Neutropenia was the DLT. Although no patient experienced DLT at the highest dose level (32 mg/m2/d), multiple treatment delays (54% of cycles) and dose reductions (34% of cycles) were required at this dose level. Others toxicities were mainly limited to grade 1 peripheral neuropathy and grade 1/2 nausea/vomiting. The relative dose-intensity of administered VNB from dose levels 3 to 6 (26 to 32 mg/m2) remained stable, whereas grade 3/4 neutropenia increased. All patients were assessable for activity; there were 10 objective responses, including one complete response (37% response rate). The present combination can be safely administered in an outpatient setting. The RD is VNB 26 mg/m2 days 1 and 8 with oxaliplatin 130 mg/m2 day 1 every 3 weeks.