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 vincristine (CABO) versus cisplatin and 5-fluorouracil (CF) versus cisplatin (C) in chemotherapy naive patients with recurrent or metastatic squamous cell carcinoma of the head and neck. The primary objectives of this study were to investigate whether the CF regimen was in anyway superior 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) methotrexate (40 mg/M2) days 1 and 15, bleomycin (10 mg) and vincristine (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 every 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 response 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 associated with performance status and prior treatment, but by multivariate analysis treatment type was the important determinant of response (p = 0.0006). Although CABO and CF were superior to C with respect to time to progression within the first 6 to 8 months after randomization, there was no overall difference in progression-free survival or survival between the three arms of the study. Both hematologic and non-hematologic toxicity were worse in the combination chemotherapy arms. Conclusion: We conclude that the CF regimen has no advantage over the CABO regimen, which in fact showed a higher complete response rate. Both combinations showed improved response rates but also more toxicity and no improvement in overall survival in comparison with cisplatin alone.