A dose-escalation study of oxaliplatin and vinorelbine in patients with advanced solid tumors

Vinorelbine (V) and oxaliplatin (OX) have shown interesting activity in a wide range of solid tumors. A phase I study was conducted in order to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of their combination in patients with refractory solid tumors.

Thirty-eight patients with histologically confirmed non-small-cell lung cancer, ovarian cancer and breast cancer who had failed at least one prior chemotherapy regimen were enrolled. The patients' median age was 60 years, 33 were female, and 27 had a performance status (WHO) of 0-1. V was administered on days 1 and 8 as a 1-hour intravenous infusion at escalated doses ranging from 20 to 27 mg/m2. OX was administered on days 1 and 8 at escalated doses ranging from 40 to 55 mg/m2, following V administration. Treatment was repeated every 3 weeks.

At the dose of V 27 mg/m2 and OX 55 mg/m2 3 out of 6 enrolled patients presented DLTs (2 patients grade 4 neutropenia and 1 treatment delay at day 8), and, thus, the recommended MTD for future phase II studies are V 27 mg/m2 and OX 50 mg/m2. A total of 131 treatment cycles were administered. Grade 3/4 neutropenia complicated 23 (18%) treatment cycles. There was one septic death. The main nonhematologic toxicities were grade 2/3 nausea/vomiting (17 cycles; 13%), grade 2 neurotoxicity (6 cycles; 5%) and grade 2/3 asthenia (21 cycles; 16%). One CR (4%), 5 PR (20%) and 4 SD (16%) were observed amongst the 25 evaluable patients. All responses were observed in patients with ovarian and breast cancer.

The results of this phase I study demonstrate that V and OX can be combined at clinically effective and relevant doses to be further evaluated in patients with breast and ovarian cancer.