Chemotherapy of advanced head and neck cancer: updated results of a randomized trial of the order of administration of sequential methotrexate and 5-fluorouracil.

One hundred and twenty-seven patients with advanced or recurrent squamous cell carcinoma of the head and neck (HNC) were randomized to treatment with methotrexate (MTX) followed 1 hour later by 5-fluorouracil (5-FU) (sequence MF), or 5-fluorouracil followed after 1 hour by methotrexate (sequence FM). One hundred and seventeen patients were evaluable for response. There was no significant difference in response rates between the MF and FM sequences. Overall, 8 patients (6.8%) achieved complete response (CR) and 46 (39.3%) partial response (PR). In 95 previously untreated patients, the overall response rate (CR + PR) was 50%, compared with 31% for previously treated patients (P = 0.02). Survival duration significantly favored the FM sequence in univariate analyses (P = 0.04). Stepwise multivariate Cox model analysis showed that poor performance status (Eastern Cooperative Oncology Group) at study entry (P less than 0.001) and prior radiotherapy (P = 0.03) were significant adverse predictors for survival. When allowance was made for these factors, a survival difference in favor of the FM sequence remained (P = 0.003). Sequential MTX followed 1 hour later by 5-FU is not recommended for treatment of HNC.