Phase II study of carboplatin and edatrexate (10-EdAM) with leucovorin rescue for patients with recurrent squamous cell carcinoma of the head and neck.

Recurrent squamous cell carcinoma of the head and neck is poorly responsive to chemotherapy in most patients; therefore, the development of new approaches is essential. Edatrexate is a new antifolate with improved preclinical antitumor activity when compared to methotrexate. The purpose of this study was to define the feasibility and efficacy of combining edatrexate with another active single agent, carboplatin in chemotherapy-naive recurrent disease. Carboplatin was given as an outpatient on day 1 at a dosage based on the formula: Dose (mg/m2) = (0.091) (creatinine clearance) (body surface area) (desired percentage change in platelet count) + 86. Edatrexate (80 mg/m2) was given on days 1, 8, and 15 of a 21 day cycle. Calcium leucovorin 15 mg was given orally every 6 h for 4 doses after edatrexate. Of the 26 patients entered on the study, 1 was inevaluable for toxicity or response and 3 patients were evaluable for toxicity only. Grade 3 or 4 neutropenia occurred in 2 patients each, and grade 3 or 4 thrombocytopenia occurred in 2 and 4 patients, respectively. Grade 3 stomatitis occurred in only two patients. Overall, major responses occurred in 2 of 22 evaluable patients (9%). The combination of carboplatin and edatrexate was not superior to the results expected with either agent alone.