Prospective, Multicenter, Phase 2 Trial of Induction Chemotherapy Followed by Bio-Chemoradiotherapy for Locally Advanced Recurrent Nasopharyngeal Carcinoma

Int J Radiat Oncol Biol Phys. 2018 Mar 1;100(3):630-638. doi: 10.1016/j.ijrobp.2017.11.038. Epub 2017 Dec 1.

Abstract

Purpose: To evaluate, in a phase 2 study, whether induction docetaxel, cisplatin, and fluorouracil (TPF) followed by weekly docetaxel and cetuximab in concurrence with intensity modulated radiation therapy can improve the treatment outcome for patients with advanced locally recurrent nasopharyngeal carcinoma (rNPC).

Methods and materials: Thirty-three patients with rNPC (T3-T4, N0-N1, M0) were recruited. Of these, 19 patients (57.6%) had stage rT3 recurrence, and the rest had stage rT4. Eight patients also had rN1 at the time of relapse. Treatment outcomes and safety were evaluated.

Results: Among these 33 patients, 1 died after 1 cycle of TPF, 5 patients withdrew from the study during the induction period because of grade ≥3 toxicities; 27 patients completed the whole course of treatment, but 1 died before any assessment could be made. The median follow-up period was 28.5 months. The progression-free survival and overall survival at 3 years for the whole group were 35.7% and 63.8%, respectively. Among the 26 patients who could be assessed after treatment, the complete response rate was 30.8%, and the locoregional control rate at 3 years was 49.2%. Temporal lobe necrosis (TLN) developed in 8 cases. The rates of grade ≥3 hearing loss, soft tissue necrosis, dysphagia, and trismus were 30.8%, 15.4%, 11.5%, and 19.2%, respectively. Overall, 5 patients died owing to acute (1 after cycle 1 TPF and 1 after completion of bio-chemoradiotherapy) or late (2 epistaxis and 1 TLN) treatment-related complications.

Conclusions: The proposed salvage treatment regimen for advanced locally recurrent NPC could achieve a better treatment outcome than seen in previous studies. However, poor tolerability of induction TPF and the high rate of TLN limit its applicability outside clinical trials.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cause of Death
  • Cetuximab / administration & dosage
  • Chemoradiotherapy / adverse effects
  • Chemoradiotherapy / methods*
  • Cisplatin / administration & dosage
  • Docetaxel / administration & dosage
  • Female
  • Fluorouracil / administration & dosage
  • Humans
  • Induction Chemotherapy / adverse effects
  • Induction Chemotherapy / methods*
  • Male
  • Middle Aged
  • Nasopharyngeal Carcinoma / mortality
  • Nasopharyngeal Carcinoma / pathology
  • Nasopharyngeal Carcinoma / therapy*
  • Nasopharyngeal Neoplasms / mortality
  • Nasopharyngeal Neoplasms / pathology
  • Nasopharyngeal Neoplasms / therapy*
  • Necrosis / etiology
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / therapy*
  • Progression-Free Survival
  • Prospective Studies
  • Radiotherapy, Intensity-Modulated* / adverse effects
  • Salvage Therapy / methods
  • Temporal Lobe / pathology
  • Temporal Lobe / radiation effects
  • Treatment Outcome

Substances

  • Docetaxel
  • Cetuximab
  • Cisplatin
  • Fluorouracil