A randomized prospective comparison of methotrexate with a combination of methotrexate, bleomycin, and cisplatin in head and neck cancer.

Combination chemotherapy with methotrexate, bleomycin, and cis-diamminedichloroplatinum (II) was compared to weekly therapy with methotrexate alone in a randomized prospective trial in 163 patients with recurrent or metastatic squamous cancer of the mucous membranes of the head and neck. The combination produced responses in 48% compared to 35% for methotrexate alone, with 16% complete remissions versus 8%, respectively. The difference in overall and complete remission rates is significant (P = 0.04) using a one-sided binary regression test. Median time to disease progression among responders was 5.8 months for the combination and 5 months for methotrexate, and median survival was 5.6 months in each group. Toxicity was similar in the two groups. Ambulatory patients, those without fixed neck nodes and those without distant metastases, responded more often. Poor performance status, distant metastases, history of heavy smoking, and adjacent organ invasion by the primary tumor were associated with shorter survival, as were weight loss, the presence of tumor in the neck, and heavy alcohol consumption. The addition of bleomycin and cisplatin to methotrexate produces more remissions, and especially complete remissions, but has not made a major impact on the course of far-advanced head and neck cancer.