Safety and toxicity analysis of oxaliplatin combined with fluorouracil or as a single agent in patients with previously treated advanced colorectal cancer

Purpose: Two consecutive compassionate use studies of oxaliplatin were conducted in the United States and Canada in more than 5,000 patients with locally advanced or metastatic colorectal carcinoma who had experienced treatment failure after at least one prior chemotherapy regimen. Patients and Methods: The main focus was safety. Patients were assigned to treatment with either single-agent oxaliplatin or oxaliplatin in combination with fluorouracil (FU) and with or without leucovorin (LV) in various regimens. Response data collection was not a trial objective, but time to treatment failure (TTF) was recorded in the first cohort (1,370 patients). Results: All treatment regimens were well tolerated, with an overall incidence of grade 3 or 4 hematologic toxicity of 23.2%, grade 3 or 4 treatment-related gastrointestinal toxicity of 26.4% (including diarrhea, vomiting, and mucositis), and grade 3 neurosensory toxicity 3.9%. Similar results were reported in the second cohort (3,806 patients), in which the eligibility criteria were much less restrictive. In the first cohort (in which 83% received prior irinotecan), median TTF was 14 weeks, and was similar for the five regimens combining oxaliplatin and FU with or without LV, but significantly shorter for the single-agent oxaliplatin arm. The overall dose-intensity of oxaliplatin was maintained at 85.5% (range, 80.6% to 94.3%) of that prescribed by protocol (average 36.7 mg/m²/wk). Conclusion: These data in a heavily pretreated patient population confirm that oxaliplatin is safe when used as a single agent or with a variety of FU-based regimens as salvage therapy in patients with advanced colorectal cancer.