A Dose Escalating Study of Oxaliplatin and High Dose Weekly Leucovorin and 5-Fluorouracil in Patients with Advanced Solid Tumors

Abstract

Purpose. To determine the dose-limiting toxicities (DLTs) and the maximum tolerated doses (MTD) of L-OHP plus 5-FU and LV in patients with advanced solid malignancies. Patients and Methods. Patients received escalated doses of L-OHP (starting dose 50 mg/m²) as a 2-hour IV infusion on Days 1 and 15, and LV (500 mg/m² as a 2-hour IV infusion) followed by escalated doses of 5FU (starting dose 1,800 mg/m²) as a 22-hour continuous IV infusion on Days 1, 8, 15, 21 every 6 weeks. DLTs were evaluated in the first cycle. Results. Fifty-two patients [median age: 66 years; PS (ECOG) 0–1 in 90 percent] were treated on 12 dose-levels. Five (10 percent) patients had received 2 prior chemotherapy regimens, 24 (46 percent) one, and 23 (44 percent) were chemo-naïve. The DLT was reached at the dose of LOHP 100 mg/m² and 5FU 2,200 mg/m². Dose-limiting events were G3 diarrhea, G3 asthenia, G4 neutropenia, and G4 thrombocytopenia. Grade 3 diarrhea was observed in 6 (12 percent) patients and Grade 3 fatigue in 6 (12 percent). One (2 percent) patient developed Grade 4 neutropenia and another (2 percent) Grade 4 thrombocytopenia. Conclusion. The MTD were L-OHP 95 mg/m² on d₁ and d₁₅ and 5FU 2,200 mg/m²/week for 4 consecutive weeks every 6 weeks.

• AIO schedule
• Oxaliplatin
• Phase I study