Cisplatin and Fluorouracil Alone or with Docetaxel in Head and Neck Cancer

TAX 324 Trial

• 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 radiation):
  • Only 30% to 50% of patients with locally advanced disease:
    • Live for three years
  • 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
• Results of the TAX 324 study here
• METHODS:
  • 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
• RESULTS:
  • 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
• CONCLUSIONS:
  • 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