Concomitant chemoradiotherapy is the standard treatment for patients with unresectable squamous cell carcinoma of the head and neck; however, induction chemotherapy with cisplatin and fluorouracil (PF) can also be a beneficial treatment. Induction chemotherapy with docetaxel plus PF (TPF) has resulted in high response rates in phase I and II studies.OBJECTIVE
To compare outcomes after treatment with PF or TPF followed by carboplatin-based chemo-radiotherapy in patients with squamous cell carcinoma of the head and neck.DESIGN
From May 1999 to December 2003, this randomized, open-label, phase III trial recruited patients with measurable, nonmetastatic, histologically proven stage III or IV squamous cell carcinoma of the oral cavity, larynx, oropharynx or hypopharynx that was unresectable. To be eligible for inclusion in the trial patients had to be aged over 18 years, with a WHO performance status of 0 or 1 and adequate bone marrow, renal and liver function. The exclusion criteria included previous chemotherapy or radiotherapy, cancer diagnosis within the previous 5 years and previous surgery for head and neck carcinoma.INTERVENTION
Patients were randomized to receive three cycles of TPF induction chemotherapy docetaxel 75 mg/m2, cisplatin 100 mg/m2, then fluorouracil 1,000 mg/mm2) or three cycles of PF induction chemotherapy (cisplatin 100 mg/m2, followed by fluorouracil 1,000 mg/m2). Both regimens were given every 3 weeks and were followed by 7 weeks of chemoradiotherapy consisting of weekly carboplatin, and radio-therapy for 5 days per week). Following completion of chemoradiotherapy, neck dissections were performed in some cases.OUTCOME MEASURE
The primary outcome was overall survival.RESULTS
A total of 501 patients started induction chemotherapy-255 with TPF and 246 with PF. The median follow-up was 42 months (minimum 24 months). Patients in the TPF group had a 30% lower risk of death (hazard ratio 0.70, 95% CI 0.54-0.90; P = 0.006). The median overall survival was 71 months in the TPF group and 30 months in the PF group (P = 0.006). The estimated 3-year survival rate was 62% in the TPF group (95% CI 56-68%) and 48% in the PF group (95% CI 42-55%; P = 0.002). The median progression-free survival was 36 months in the TPF group and 13 months in the PF group. The overall response rate was 72% in the TPF group and 64% in the PF group (P = 0.07). Patients in the TPF group experienced higher rates of neutropenia and febrile neutropenia than were seen in the PF group.CONCLUSION
Induction chemotherapy with TPF results in higher survival rates than induction chemotherapy with PF in patients with stage III-IV squamous cell carcinoma of the head and neck.