Phase III study comparing cisplatin plus fluorouracil to paclitaxel, cisplatin, and fluorouracil induction chemotherapy followed by chemoradiotherapy in locally advanced head and neck cancer

Purpose To compare the antitumor activity and toxicity of the two induction chemotherapy treatments of paclitaxel, cisplatin, and fluorouracil (FU; PCF) versus standard cisplatin and FU (CF), both followed by chemoradiotherapy (CRT), in locally advanced head and neck cancer (HNC). Patients and Methods Eligibility criteria included biopsy-proven, previously untreated, stage III or IV locally advanced HNC. Patients received either CIF (cisplatin 100 mg/m(2) on day 1 plus FU 1 mg/m(2) continuous infusion on days 1 through 5) or PCIF (paclitaxel 175 mg/m(2) on day 1, cisplatin 100 mg/m(2) on day 2, and FU 500 mg/m(2) continuous infusion on days 2 through 6); both regimens were administered for three cycles every 21 days. Patients with complete response (CB) or partial 100 mg/m(2) response of greater than 80% in primary tumor received additional CRT (cisplatin on days 1, 22, and 43 plus 70 Gy). Results A total of 382 eligible patients were randomly assigned to CF (n = 193) or PCF (n = 189). The CR rate was 14% in the CIF arm v33% in the PCIF arm (P < .001). Median time to treatment failure was 12 months in the CF arm compared with 20 months in the PCIF arm (log-rank test, P = .006; Tarone-Ware, P = .003). PCIF patients had a trend to longer overall survival (OS; 37 months in CIF arm v 43 months in PCF arm; log-rank test, P =.06; Tarone-Ware, P = .03). This difference was more evident in patients with unresectable disease (OS: 26 months in CIF arm v 36 months in PCIF arm; log-rank test, P = .04; Tarone-Ware, P = .03). CF patients had a higher occurrence of grade 2 to 4 mucositis than PCF patients (53% v 16%, respectively; P < .001). Conclusion Induction chemotherapy with PCIF was better tolerated and resulted in a higher CR rate than CF. However, new trials that compare induction chemotherapy plus CRT versus CRT alone are needed to better define the role of neoadjuvant treatment.