Vinorelbine, cisplatin, and 5-fluorouracil as initial treatment for previously untreated, unresectable squamous cell carcinoma of the head and neck results of a Phase II multicenter study

BACKGROUND. The combination of vinorelbine (VNR), cisplatin (CDDP), and 5-fluoro- uracil (5-FU) has previously been shown to be active in recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCHNC). This multicenter Phase II study was carried out with the aim of evaluating the effectiveness of this combination in patients with previously untreated, unresectable locally advanced SCHNC. METHODS. Sixty patients with previously untreated, unresectable SCHNC were treated with CDDP 80 mg/ m 2 on Days 1, 5-FU 600 mg/ m 2 as a 4-hour infusion on Days 2–5, and VNR 25 mg/ m 2 iv bolus on Days 2 and 8. There were 15 patients with laryngeal carcinoma, 19 patients with oropharyngeal carcinoma, 15 with carci- noma in the oral cavity, 5 with carcinoma in the hypopharynx, and 4 with carci- noma in the maxillary sinus. Most patients (78%) had Stage IV disease. After achievement of the best possible objective response, patients were subjected to definitive locoregional treatment, i.e., radiotherapy and/or surgery, as appropriate. RESULTS. All patients completed the induction chemotherapy. After a mean of 3.86 cycles per patient, the overall response rate was 88% (95% confidence interval [CI], 82–94%), with a complete response rate of 23% (95% CI, 14–26%). Complete responses were more frequently seen in patients with N0-1 disease than in those with N2–3 disease (P = 0.037). No other statistically significant correlation between type of response and extent of disease was noted. Toxicity consisted mainly of myelosuppression and gastrointestinal side effects. After definitive locoregional treatment, 58% of patients were clinically free of disease. These patients included those who had complete response after induction chemotherapy, 19 of 39 patients who had partial response, and 2 with stable disease. Median disease free survival was 16 months, and median overall survival was 23 months. CONCLUSIONS. The combination regimen of CDDP, 5-FU, and VNR was very active in previously untreated SCHNC. It was well tolerated in most cases, and neurotoxic- ity was not a major side effect. This regimen, which does not require hospitalization, should be compared with standard chemotherapy, such as the combination of CDDP and continuous-infusion 5-FU.