Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer

N Engl J Med. 2004 May 6;350(19):1945-52. doi: 10.1056/NEJMoa032641.

Abstract

Background: We compared concomitant cisplatin and irradiation with radiotherapy alone as adjuvant treatment for stage III or IV head and neck cancer.

Methods: After undergoing surgery with curative intent, 167 patients were randomly assigned to receive radiotherapy alone (66 Gy over a period of 6 1/2 weeks) and 167 to receive the same radiotherapy regimen combined with 100 mg of cisplatin per square meter of body-surface area on days 1, 22, and 43 of the radiotherapy regimen.

Results: After a median follow-up of 60 months, the rate of progression-free survival was significantly higher in the combined-therapy group than in the group given radiotherapy alone (P=0.04 by the log-rank test; hazard ratio for disease progression, 0.75; 95 percent confidence interval, 0.56 to 0.99), with 5-year Kaplan-Meier estimates of progression-free survival of 47 percent and 36 percent, respectively. The overall survival rate was also significantly higher in the combined-therapy group than in the radiotherapy group (P=0.02 by the log-rank test; hazard ratio for death, 0.70; 95 percent confidence interval, 0.52 to 0.95), with five-year Kaplan-Meier estimates of overall survival of 53 percent and 40 percent, respectively. The cumulative incidence of local or regional relapses was significantly lower in the combined-therapy group (P=0.007). The estimated five-year cumulative incidence of local or regional relapses (considering death from other causes as a competing risk) was 31 percent after radiotherapy and 18 percent after combined therapy. Severe (grade 3 or higher) adverse effects were more frequent after combined therapy (41 percent) than after radiotherapy (21 percent, P=0.001); the types of severe mucosal adverse effects were similar in the two groups, as was the incidence of late adverse effects.

Conclusions: Postoperative concurrent administration of high-dose cisplatin with radiotherapy is more efficacious than radiotherapy alone in patients with locally advanced head and neck cancer and does not cause an undue number of late complications.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / radiotherapy*
  • Carcinoma, Squamous Cell / surgery
  • Cisplatin / adverse effects
  • Cisplatin / therapeutic use*
  • Combined Modality Therapy / adverse effects
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Head and Neck Neoplasms / drug therapy*
  • Head and Neck Neoplasms / mortality
  • Head and Neck Neoplasms / radiotherapy*
  • Head and Neck Neoplasms / surgery
  • Humans
  • Male
  • Middle Aged
  • Radiotherapy / adverse effects
  • Risk
  • Survival Rate

Substances

  • Antineoplastic Agents
  • Cisplatin

Grants and funding