A randomized phase three trial of the treatment of squamous-cell carcinoma of the head and neck compared induction chemotherapy with docetaxel plus cisplatin and fluorouracil (TPF) with cisplatin and fluorouracil (PF), followed by chemoradiotherapy.
Squamous-cell carcinoma of the head and neck accounts for 5% of newly diagnosed cancers in adults in the United States and 8% of cancers worldwide. The disease is potentially curable at an early stage, but most patients present with locally advanced disease. After standard therapy (surgery and irradiation), only 30% to 50% of patients with locally advanced disease live for three years, and locoregional recurrences or distant metastases develop in 40% to 60% of them. Various strategies to improve outcomes by coordinating chemotherapy with surgery and radiotherapy have been tried, but the optimal schedule for integrating chemotherapy into the management of this disease has yet to be defined.
Although chemoradiotherapy (radiotherapy plus concurrent chemotherapy) has become the standard of care for patients with unresectable squamous-cell carcinoma of the head and neck and for organ preservation, induction chemotherapy with cisplatin and fluorouracil (PF) also has benefits in this disease. A comprehensive meta-analysis showed that induction chemotherapy (i.e., chemotherapy as the initial treatment) with PF significantly improved the rate of survival at 5 years, as compared with standard radiotherapy plus surgery in patients with locally advanced disease.
Docetaxel (Taxotere, Sanofi-Aventis) has substantial activity when administered alone in patients with recurrent or incurable disease. In phase 1 and phase 2 studies of docetaxel plus cisplatin and fluorouracil (TPF) in the treatment of locally advanced squamous-cell carcinoma of the head and neck, including phase 2 studies of treatment with curative intent, clinical and pathological response rates have been high and survival has been prolonged.
Two phase 3 trials in which induction chemotherapy with TPF or PF was followed by radiotherapy (the European Organization for Research and Treatment of Cancer [EORTC] 24971 / TAX 323 study by Vermorken et al.) or chemoradiotherapy (TAX 324) in locally advanced disease have now been completed. They report on the results of the TAX 324 study here.
They randomly assigned 501 patients (all of whom had stage III or IV disease with no distant metastases and tumors considered to be unresectable or were candidates for organ preservation) to receive either TPF or PF induction chemotherapy, followed by chemoradiotherapy with weekly carboplatin therapy and radiotherapy for 5 days per week. The primary end point was overall survival.
With a minimum of 2 years of follow-up (≥3 years for 69% of patients), significantly more patients survived in the TPF group than in the PF group (hazard ratio for death, 0.70; P=0.006). Estimates of overall survival at 3 years were 62% in the TPF group and 48% in the PF group; the median overall survival was 71 months and 30 months, respectively (P=0.006). There was better locoregional control in the TPF group than in the PF group (P=0.04), but the incidence of distant metastases in the two groups did not differ significantly (P=0.14). Rates of neutropenia and febrile neutropenia were higher in the TPF group; chemotherapy was more frequently delayed because of hematologic adverse events in the PF group.
Patients with squamous-cell carcinoma of the head and neck who received docetaxel plus cisplatin and fluorouracil induction chemotherapy plus chemoradiotherapy had a significantly longer survival than did patients who received cisplatin and fluorouracil induction chemotherapy plus chemoradiotherapy. (ClinicalTrials.gov number, NCT00273546. opens in new tab.)