Methotrexate and leucovorin double-modulated 5-fluorouracil combined with cisplatin (MPFL) in metastatic/recurrent head and neck cancer

Background: To determine the efficacy and safety profile of the combination of cisplatin and 5-fluorouracil modulated both by methotrexate and leucovorin in metastatic/recurrent squamous cell carcinoma of the head and neck. Methods: Twenty-eight patients were treated with cisplatin 40 mg/m²/day continuous infusion for 24 hours on day 1; high-dose 5-fluorouracil 2,000 mg/m²/day and leucovorin 100 mg/m²/day continuous infusion for 48 hours on days 1 and 2; methotrexate 40 mg/m²/day as a bolus infusion 4 hours before 5-fluorouracil and leucovorin on day 1. The treatment was repeated every 2 weeks in a cycle. Results: The overall response rate was 25%, and 14% of the patients achieved stable disease status. Subgroup analysis demonstrated significantly improved overall survival in the disease-control group (12.0 months vs. 5.3 months, p < 0.001). Only 3 (10.7%) patients developed grade 3-4 neutropenia, and none developed grade 3-4 non-hematologic toxicity. Conclusion: This multiagent-containing regimen has an excellent safety profile and improved survival in disease-control group of patients with metastatic/recurrent squamous cell carcinoma of the head and neck.