RTOG 0129 Long-Term Results: No Differences in Survival or Toxicity With Accelerated vs Standard Fractionation Plus Cisplatin in Head and Neck Cancer
As reported in the Journal of Clinical Oncology by Nguyen-Tan et al, long-term follow-up in the phase III Radiation Therapy Oncology Group (RTOG) 0129 trial indicates no difference in overall survival or late toxicity with use of accelerated vs standard radiation therapy plus cisplatin in patients with locally advanced head and neck cancer. As in the previous report from the trial, which also showed no overall survival difference, patients with human papillomavirus (HPV) p16-related oropharyngeal carcinoma had significantly better outcomes vs those with p16-negative disease.
Study Details
In the trial, 721 patients with stage III to IV carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx were randomly assigned between July 2002 and June 2005 to cisplatin plus accelerated fractionation with a concomitant boost (n = 360) or standard fractionation (n = 361). Radiation therapy schedules were 72 Gy in 42 fractions over 6 weeks in the accelerated fractionation group and 70 Gy in 35 fractions over 7 weeks in the standard fractionation group. Cisplatin was given at 100 mg/m2 once every 3 weeks for two (accelerated fractionation group) or three (standard fractionation group) cycles.
No Efficacy Differences
Median follow-up was 7.9 years (range = 0.3–10.1 years) in 355 surviving patients. There were no significant differences between the standard fractionation and accelerated fractionation plus concomitant boost groups in overall survival (hazard ratio [HR] = 0.96, P = .37; 5-year = 57% vs 60%, 8-year estimate = 48% vs48%), progression-free survival (HR = 1.02, P = .52; 5-year = 49% vs 50%, 8-year estimate = 42% vs41%), locoregional failure rate (HR = 1.08, P = .78; 5-year = 31% vs 34%, 8-year estimate = 37% vs39%), or rate of distant metastases (HR = 0.83, P = .16; 5-year = 14.5% vs 11.5%, 8-year estimate = 15% vs13%).
Effect of p16 Status
Among 215 patients with p16-positive and 101 with p16-negative oropharyngeal cancer, p16-positive patients had significantly better overall survival (HR = 0.34, 95% confidence interval [CI] = 0.22–0.52), progression-free survival (HR = 0.43, 95% CI = 0.29–0.64), and locoregional failure rate (HR = 0.29, 95% CI = 0.17–0.48) but not distant metastases rate (HR = 0.59, 95% CI = 0.26–1.35) after adjustment for prognostic covariates. Eight-year rates were 70.9% vs 30.2% for overall survival, 64.0% vs 23.3% for progression-free survival, 19.5% vs 52.4% for locoregional failure, and 10.3% vs 16.1% for distant metastases.
Toxicity
There were no significant differences in grade 3 to 5 acute or late toxicities between the standard fractionation and accelerated fractionation groups or according to p16 status. Toxicity rates were 74% vs 72.5% for nonhematologic toxicity ≤ 90 days from the start of radiation therapy, 39% vs 33% for mucositis/stomatitis at ≤ 90 days and 4% vs 5% at > 90 days, and 82% vs 77% for any toxicity ≤ 90 days and 36.5% vs 38% at > 90 days. Death occurred in 1.9% vs 3.3% of patients within 30 days of completing therapy (P = .26). Feeding tubes were used in 25% vs 22% of patients before treatment (P = .43), 69% vs 67% (P = .80) by completion of treatment, 29% vs 26% at 1 year after treatment (P = .53), and 6% vs 13% at 5 years after treatment (P = .08).
The investigators concluded: “When combined with cisplatin, [accelerated fractionation with a concomitant boost] neither improved outcome nor increased late toxicity in patients with [locally advanced head and neck cancer]. Long-term high survival rates in p16-positive patients with oropharyngeal cancer support the ongoing efforts to explore deintensification.”
Phuc Felix Nguyen-Tan, MD, of Centre Hospitalier de l’Université de Montréal Hôpital Notre-Dame, is the corresponding author for the Journal of Clinical Oncology article.
The study was supported by grants from the Radiation Therapy Oncology Group and National Cancer Institute. For full disclosures of the study authors, visit jco.ascopubs.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
