A Phase I Study of an Oral Simulated FOLFOX with High Dose Capecitabine

Background: A phase I study of high-dose capecitabine given over 2 days, along with oxaliplatin, bolus 5FU and leucovorin (LV), was designed to simulate FOLFOX6 without the need for infusional 5FU. Methods: Schedule A included oxaliplatin 100 mg/m2, 5FU 400 mg/m2, and LV 20 mg/m2 (all given IV on days 1 and 15, 28 day cycle). Capecitabine was administered orally every 8 h × 6 doses, days 1 and 15. Schedule B excluded 5FU and LV, maintaining oxaliplatin and capecitabine. Pharmacokinetics were performed for capecitabine for 6 patients on each schedule. Results: 36 patients were treated. The dose-limiting toxicities seen included nausea, dehydration, fatigue, hypotension and confusion. Minimal palmar-plantar erythrodysesthesia was seen. Myelosuppression was common, but not a dose limiting toxicity. The pharmacokinetic parameters for capecitabine were unaltered. Conclusion: Using capecitabine to mimic FOLFOX6 is feasible and well tolerated with a toxicity profile that differs from standard 14-day capecitabine dosing, with less palmar-plantar erythrodysesthesia. The phase II dose for capecitabine in combination with oxaliplatin, 5FU, and LV is 1,500 mg/m2/dose or 2,250 mg/m2/dose in the absence of bolus 5FU/LV.