RANDOMIZED PHASE-III TRIAL OF EDATREXATE VERSUS METHOTREXATE IN PATIENTS WITH METASTATIC AND OR RECURRENT SQUAMOUS-CELL CARCINOMA OF THE HEAD AND NECK - A EUROPEAN ORGANIZATION FOR RESEARCH AND TREATMENT OF CANCER HEAD AND NECK-CANCER COOPERATIVE GROUP-STUDY/

Purpose: To compare the response rates and the toxicity of the new ant ifolate edatrexate (EDX) with that of methotrexate (MTX) in a randomiz ed trial in patients with metastatic or recurrent squamous cell cancer of the head and neck (SCC) and to compare the durations of response a nd survivor. Patients and Methods: Two hundred seventy-three patients with SCC were randomized to receive either EDX or MTX as a weekly intr avenous (IV) bolus injection. Doses of EDX were initially 80 mg/m(2)/w k, but because of the toxicity, this was later reduced to 70 mg/m(2)/w k. MTX was administered at a dose of 40 mg/m(2)/wk throughout. In both arms, two dose increments of 10% were scheduled in case of no toxicit y. Results: Of 264 eligible patients, 131 were treated with EDX and 13 3 with MTX. There were five treatment-related deaths: four on EDX and one on MTX, Overall, toxicity was similar in both arms; however, stoma titis, skin toxicity, and hair loss were more pronounced on the EDX ar m, The overall response rate was 21% (six complete responses [CRs] and 21 partial responses [PRs]) for EDX and 16% (nine CRs and 12 PRs) for MTX (P = .392). Responses were mainly seen in patients with locoregio nal disease, Tumors that originated from the hypopharynx responded poo rly in comparison to tumors from other sites. The median duration of r esponse was 6.1 months for EDX and 6.4 months for MTX (log-rank P = .2 62). There was no difference in overall or progression-free survival. The median survival duration was 6 months on both treatment groups, Co nclusion: Both EDX and MTX ore moderately active against SCC. In this large phase III study, response rates, time to treatment failure, and overall survival appeared to be similar for both antifolates. However, EDX had more side effects than MTX and therefore cannot be recommende d for routine palliative treatment of patients with SCC.