Cisplatin, Fluorouracil, and Docetaxel in Unresectable Head and Neck Cancer

TLDR

Phase 2 studies suggest that adding docetaxel to cisplatin and fluorouracil (TPF) improves outcomes in squamous‑cell carcinoma of the head and neck. We randomized 358 patients with stage III/IV unresectable squamous‑cell head and neck cancer to receive either induction TPF (docetaxel + cisplatin day 1, fluorouracil continuous infusion days 1‑5) or PF every 3 weeks for four cycles, followed by radiotherapy within 4‑7 weeks if no progression. TPF induction improved median progression‑free survival to 11.0 months versus 8.2 months (HR 0.72, P = 0.007) and overall survival to 18.8 months versus 14.5 months (27% risk reduction, P = 0.02), but was associated with higher rates of grade 3/4 leukopenia and neutropenia, while PF had more thrombocytopenia, nausea, vomiting, stomatitis, and hearing loss, with 2.3% versus 5.5% death from toxicity. ClinicalTrials.gov identifier: NCT00003888.

Abstract

Phase 2 studies suggest that the standard regimen of cisplatin and fluorouracil (PF) plus docetaxel (TPF) improves outcomes in squamous-cell carcinoma of the head and neck. We compared TPF with PF as induction chemotherapy in patients with locoregionally advanced, unresectable disease.We randomly assigned eligible patients between the ages of 18 and 70 years who had stage III or stage IV disease and no distant metastases to receive either TPF (docetaxel and cisplatin, day 1; fluorouracil by continuous infusion, days 1 to 5) or PF every 3 weeks for four cycles. Patients without progression of disease received radiotherapy within 4 to 7 weeks after completing chemotherapy. The primary end point was progression-free survival.A total of 358 patients underwent randomization, with 177 assigned to the TPF group and 181 to the PF group. At a median follow-up of 32.5 months, the median progression-free survival was 11.0 months in the TPF group and 8.2 months in the PF group (hazard ratio for disease progression or death in the TPF group, 0.72; P=0.007). Treatment with TPF resulted in a reduction in the risk of death of 27% (P=0.02), with a median overall survival of 18.8 months, as compared with 14.5 months in the PF group. There were more grade 3 or 4 events of leukopenia and neutropenia in the TPF group and more grade 3 or 4 events of thrombocytopenia, nausea, vomiting, stomatitis, and hearing loss in the PF group. The rates of death from toxic effects were 2.3% in the TPF group and 5.5% in the PF group.As compared with the standard regimen of cisplatin and fluorouracil, induction chemotherapy with the addition of docetaxel significantly improved progression-free and overall survival in patients with unresectable squamous-cell carcinoma of the head and neck. (ClinicalTrials.gov number, NCT00003888 [ClinicalTrials.gov]. ).