Preoperative chemotherapy in advanced resectable OCSCC: long-term results of a randomized phase III trial

Ann Oncol. 2014 Feb;25(2):462-6. doi: 10.1093/annonc/mdt555. Epub 2014 Jan 8.

Abstract

Background: Data on preoperative chemotherapy in resectable oral cavity cancer are conflicting. We present the long-term results of a randomized trial of induction chemotherapy in resectable oral cavity cancer.

Patients and methods: A randomized, parallel, multicentre trial evaluated the impact of three cycles of cisplatin 100 mg/m2 and fluorouracil 1000 mg/m2 (120-h infusion administered every 21 days) in stage T2-T4, N0-N2, previously untreated patients with advanced disease. Control group received upfront surgery. Postoperative radiation was offered to both arms when pathologic risk features were identified. The co-primary end points were the occurrence of locoregional or distant tumour relapse, and death.

Results: Among the 198 enrolled patients, with a median follow-up of 11.5 years, there was no difference in the incidence of locoregional relapse between chemotherapy and control group (P=0.6337), nor in distant metastasis development (P=0.1527). There was also no difference between groups in overall survival (P=0.3402). Patients with a pathological complete response (pCR) had higher probability of survival than those without (10-year OS: 76.2% versus 41.3%, P=0.0004). Late toxicities in patients with a minimum follow-up of 60 months (42 in each group) were similar between arms, except from fibrosis (cumulative incidence 40% versus 22% in chemotherapy arm) and grade 2 dysphagia (14% versus 5%).

Conclusions: Long-term follow-up of this randomized trial confirmed the absence of survival benefit with preoperative chemotherapy in oral cavity cancer. Late toxicity was similar in the two arms except for fibrosis and dysphagia, which were less in the chemotherapy arm. The survival benefit for patients achieving a pCR was maintained.

Keywords: cisplatin; fluorouracil; induction chemotherapy; pathological complete response; randomised trial; resectable oral cavity cancer.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / therapy*
  • Chemotherapy, Adjuvant
  • Cisplatin / administration & dosage
  • Disease-Free Survival
  • Fluorouracil / administration & dosage
  • Follow-Up Studies
  • Humans
  • Induction Chemotherapy
  • Kaplan-Meier Estimate
  • Mouth Neoplasms / mortality
  • Mouth Neoplasms / therapy*
  • Preoperative Period
  • Proportional Hazards Models
  • Treatment Outcome

Substances

  • Cisplatin
  • Fluorouracil