A multi-center phase Ib study of oxaliplatin (NSC#266046) in combination with fluorouracil and leucovorin in pediatric patients with advanced solid tumors

Background: Platinum agents have been used for a variety of cancers, including pivotal use in pediatric tumors for many years. Oxaliplatin, a third generation platinum, has a different side effect profile and may provide improved activity in pediatric cancers. Procedure: Patients 21 years or younger with progressive or refractory malignant solid tumors, including tumors of the central nervous system were enrolled on this multi-center open label, non-randomized Phase 1 dose escalation study. The study used a standard 3+3 dose escalation design with 2 dose levels (85 and 100mg/m²) with an expansion cohort of 15 additional patients at the recommended dose. Patients received oxaliplatin at the assigned dose level and 5-fluorouracil (5-FU) bolus 400mg/m² followed by a 46-hour 5-FU infusion of 2,400mg/m² every 14 days. The leucovorin dose was fixed at 400mg/m² for all cohorts. Results: Thirty-one evaluable patients were enrolled, 8 at 85mg/m² and 23 at 100mg/m² for a total of 121 courses. The median age was 12 years (range 2-19 years). The main toxicities were hematologic, primarily neutrophils and platelets. The most common non-hematologic toxicities were gastrointestinal. Stable disease was noted in 11 patients (54% of evaluable patients) and 1 confirmed partial response in a patient with osteosarcoma. Conclusions: The maximum planned dose of oxaliplatin at 100mg/m² per dose in combination with 5-FU and leucovorin was safe and well tolerated and in this patient population. This combination demonstrated modest activity in patients with refractory or relapsed solid tumor and warrants further study.