Originally published as JCO Early Release 10.1200/JCO.2004.00.1990 on November 7 2005

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Phase III Study Comparing Cisplatin Plus Fluorouracil to Paclitaxel, Cisplatin, and Fluorouracil Induction Chemotherapy Followed by Chemoradiotherapy in Locally Advanced Head and Neck Cancer

From the Hospital Universitario Doce de Octubre de Madrid, Madrid; Hospital de la Santa Creu I Sant Pau, Sant Pau; Hospital Miguel Servet de Zaragoza; Hospital Clínico Universitario de Zaragoza, Zaragoza; Hospital Clínico Universitario de Valencia, Valencia; Hospital del Mar de Barcelona, Barcelona; Hospital San Juan de Alicante; Hospital General de Alicante, Alicante; Hospital Universitario Marqués de Valdecilla de Santander, Santander; Fundación Jiménez Díaz, Madrid; Hospital Virgen del Rocío de Sevilla, Sevilla; Hospital Sant Joan de Reus, Reus; Hospital Virgen de las Nieves de Granada, Granada; Hospital Ntra Sra de Aranzazu, Aranzazu; and Bristol-Myers Squibb, Madrid, Spain

Address reprint requests to Ricardo Hitt, MD, PhD, Servicio de Oncología Médica, Hospital Universitario 12 de Octubre de Madrid, Carretera de Andalucía, km 5,400, 28041, Madrid, Spain; e-mail: rhitt{at}h12o.es; CC: rhitt{at}telefonica.net

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 CF (cisplatin 100 mg/m² on day 1 plus FU 1,000 mg/m² continuous infusion on days 1 through 5) or PCF (paclitaxel 175 mg/m² on day 1, cisplatin 100 mg/m² on day 2, and FU 500 mg/m² continuous infusion on days 2 through 6); both regimens were administered for three cycles every 21 days. Patients with complete response (CR) or partial response of greater than 80% in primary tumor received additional CRT (cisplatin 100 mg/m² 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 CF arm v 33% in the PCF arm (P < .001). Median time to treatment failure was 12 months in the CF arm compared with 20 months in the PCF arm (log-rank test, P = .006; Tarone-Ware, P = .003). PCF patients had a trend to longer overall survival (OS; 37 months in CF 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 CF arm v 36 months in PCF 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 PCF 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.

Supported by Bristol-Myers Squibb.

Presented in part at the 39th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 31-June 3, 2003.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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