Effects of induction docetaxel, platinum, and fluorouracil chemotherapy in patients with stage III or IVA/B nasopharyngeal cancer treated with concurrent chemoradiation therapy: Final results of 2 parallel phase 2 clinical trials

Cancer. 2017 Jun 15;123(12):2258-2267. doi: 10.1002/cncr.30566. Epub 2017 Feb 13.

Abstract

Background: The effects of docetaxel, platinum, and fluorouracil (TPF) induction chemotherapy plus concurrent chemoradiotherapy (CCRT) on locoregionally advanced nasopharyngeal cancer (NPC) are unclear. This study examined the long-term outcomes of the addition of this regimen to CCRT for stage III and IVA/B NPC.

Methods: Two parallel, single-arm phase 2 trials were performed synchronously to evaluate the efficacy and toxicity of TPF-based induction chemotherapy in patients with stage III or IVA/B NPC. The induction chemotherapy, which preceded standard intensity-modulated radiation therapy/platinum-based chemoradiation, consisted of 3 cycles of docetaxel (75 mg/m2 on day 1), cisplatin (75 mg/m2 on day 1), and a continuous infusion of fluorouracil (500 mg/m2 /d on days 1-5) every 4 weeks. The primary endpoint for both trials was 5-year overall survival (OS).

Results: Between January 2007 and July 2010, 52 eligible patients with stage III NPC and 64 eligible patients with nonmetastatic stage IV NPC were accrued to the 2 trials. With a median follow-up of 67 months, the 5-year OS, progression-free survival, distant metastasis-free survival, and local progression-free survival (LPFS) rates were all improved in comparison with historical benchmarks for patients with stage III or IVA/IVB NPC. Multivariate analyses indicated that T and N classifications (T1/T2 vs T3/T4 and N3 vs N0-N2) were the only significant prognosticators for OS. The number of induction chemotherapy cycles was the only significant prognostic factor for predicting LPFS.

Conclusions: TPF-based induction chemotherapy appears to significantly improve outcomes in comparison with historical data when it is administered before CCRT for locoregionally advanced NPC. A phase 3 trial is currently being performed to confirm this benefit. Cancer 2017;123:2258-2267. © 2017 American Cancer Society.

Keywords: intensity-modulated radiation therapy; nasopharyngeal cancer; neoadjuvant chemotherapy; taxane.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma / drug therapy*
  • Carcinoma / pathology
  • Chemoradiotherapy
  • Cisplatin / administration & dosage
  • Disease-Free Survival
  • Docetaxel
  • Female
  • Fluorouracil / administration & dosage
  • Humans
  • Induction Chemotherapy / methods*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / drug therapy*
  • Nasopharyngeal Neoplasms / pathology
  • Neoadjuvant Therapy / methods*
  • Neoplasm Staging
  • Prognosis
  • Radiotherapy, Intensity-Modulated
  • Survival Rate
  • Taxoids / administration & dosage

Substances

  • Taxoids
  • Docetaxel
  • Cisplatin
  • Fluorouracil