Promising long-term results with attenuated adverse effects by methotrexate-containing sequential chemoradiation therapy in locally advanced head and neck squamous cell carcinoma

Objective: To reduce severe acute and late toxicities without compromising organ preservation survival in patients with locoregionally advanced head and neck squamous cell carcinoma, we performed three-drug induction methotrexate-cisplatin-fluorouracil with weekly cisplatin-fluorouracil concurrent chemoradiation. Methods: Two induction courses of methotrexate (40 mg/m²/day, days 1, 8 and 15), cisplatin and 5-fluorouracil (25 and 750 mg/m²/day, days 1-4) were given in new diagnoses of patients with non-nasopharyngeal locoregionally advanced head and neck squamous cell carcinoma. Responders received concurrent chemoradiation with weekly cisplatin (20 mg/m²/day) and 5-fluorouracil (400 mg/m²/day) on day 1. Results: Among 57 patients (58% with Stage IV and hypopharyngeal cancer), the rates of Grade 3-4 toxicity were 30 and 74% during induction and CCRT, respectively. A total of 49 patients completed induction and began concurrent chemoradiation; 47 (96%) completed all planned treatment. With a median follow-up of 62 months (range 19-83 months) for the current survivors, the 3-year overall and disease-specific survival estimates were 50 and 58%, respectively. The 3-year organ preservation survival was 74% in patients who achieved complete remission after concurrent chemoradiation, and 96% of current survivors are tracheotomy and feeding tube-free. No patient without local/regional failure suffered from distant metastasis. Conclusions: Methotrexate-cisplatin-fluorouracil induction chemotherapy followed by weekly cisplatin-fluorouracil concurrent chemoradiation is an acute and late toxicityacceptable protocol without attenuating organ preservation survival in patients with locoregionally advanced head and neck squamous cell carcinoma. In this patient cohort with advanced head and neck squamous cell carcinoma, overall and organ preservation survivals were encouraging, and provided promising long-term benefits of this approach.