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


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 1000 [corrected] 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).


CONCLUSIONS
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.
Hitt
Ricardo
R
Servicio de Oncología Médica, Hospital Universitario 12 de Octubre de Madrid, Carretera de Andalucía, km 5,400, 28041, Madrid, Spain. rhitt@h12o.es
López-Pousa
Antonio
A
Martínez-Trufero
Javier
J
Escrig
Vicente
V
Carles
Joan
J
Rizo
Alfredo
A
Isla
Dolores
D
Vega
M Eugenia
ME
Martí
Juan L
JL
Lobo
Francisco
F
Pastor
Pedro
P
Valentí
Vicente
V
Belón
Joaquín
J
Sánchez
Miguel A
MA
Chaib
Carlos
C
Pallarés
Cinta
C
Antón
Antonio
A
Cervantes
Andrés
A
Paz-Ares
Luis
L
Cortés-Funes
Hernán
H
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000628:therapy*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D052016:Mucositis / Q000139:chemically induced; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000628:therapy; D009503:Neutropenia / Q000139:chemically induced; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D010349:Patient Compliance; D011446:Prospective Studies; D018714:Radiotherapy, Adjuvant; D012074:Remission Induction; D013030:Spain; D016019:Survival Analysis; D016896:Treatment Outcome
D017239:Paclitaxel; D002945:Cisplatin; D005472:Fluorouracil