RANDOMIZED COMPARISON OF CISPLATIN, METHOTREXATE, BLEOMYCIN AND VINCRISTINE (CABO) VERSUS CISPLATIN AND 5-FLUOROURACIL (CF) VERSUS CISPLATIN (C) IN RECURRENT OR METASTATIC SQUAMOUS-CELL CARCINOMA OF THE HEAD AND NECK - A PHASE-III STUDY OF THE EORTC HEAD AND NECK-CANCER COOPERATIVE GROUP

Background. The EORTC Head and Neck Cancer Cooperative Group conducted a randomized comparison of cisplatin, methotrexate, bleomycin and vin cristine (CABO) versus cisplatin and 5-fluorouracil (CF) versus cispla tin (C) in chemotherapy naive patients with recurrent or metastatic sq uamous cell carcinoma of the head and neck. The primary objectives of this study were to investigate whether the CF regimen was in anyway su perior to the CABO regimen and to detect any superiority of these two combinations over cisplatin alone. Patients and methods: Three hundred eighty-two patients were randomized to one of three treatments: (1) m ethotrexate (40 mg/M2) days 1 and 15, bleomycin (10 mg) and vincristin e (2 mg) days 1, 8 and 15, cisplatin (50 mg/M2) day 4, repeated every 21 days, (2) cisplatin (100 mg/M2) and 5-FU (1 g/m2 x 4), repeated eve ry 21 days, and (3) cisplatin (50 Mg/M2) days 1 and 8, repeated every 28 days. After 3 cycles, all responding and stable disease patients in the three arms of the study continued with cisplatin alone. Results: The overall response rates to CABO (34%) and CF (31%) were superior to C (15%) (p < 0.001, p = 0.003, respectively). In addition, complete r esponse rate to CABO (9.5%) was superior to that of C (2.5%) (p = 0.02 ), and also superior to that of CF (1.7%) (p = 0.01). Response was ass ociated with performance status and prior treatment, but by multivaria te analysis treatment type was the important determinant of response ( p = 0.0006). Although CABO and CF were superior to C with respect to t ime to progression within the first 6 to 8 months after randomization, there was no overall difference in progression-free survival or survi val between the three arms of the study. Both hematologic and non-hema tologic toxicity were worse in the combination chemotherapy arms. Conc lusion: We conclude that the CF regimen has no advantage over the CABO regimen, which in fact showed a higher complete response rate. Both c ombinations showed improved response rates but also more toxicity and no improvement in overall survival in comparison with cisplatin alone.