The addition of amifostine to carboplatin and paclitaxel based chemoradiation in locally advanced non-small cell lung cancer: long-term follow-up of Radiation Therapy Oncology Group (RTOG) randomized trial 9801

Abstract

Introduction: We report the long-term results of RTOG 9801, a randomized trial investigating the ability of amifostine, a radioprotector, to reduce chemoradiation-induced esophagitis.

Methods: Patients with stages II and IIIA/B non-small-cell lung cancer received induction paclitaxel 225 mg/m2 intravenously (IV) and carboplatin area under the curve (AUC) 6 both days 1 and 22, followed by concurrent weekly paclitaxel (50 mg/m2) and carboplatin (AUC 2), with hyperfractionated radiation therapy (69.6 Gy at 1.2 Gy BID). Patients were randomly assigned to amifostine (AM) 500 mg IV four times per week or no-AM during chemoradiotherapy. Stratification factors included age (<70 vs. ≥70 years), stage and performance status.

Results: 243 patients (pts) were enrolled; 120 received AM, 123 received no-AM. Two pts on each arm were found ineligible. Overall, 85% of patients were ≤70 years; 75% had a KPS ≥90. 34% had squamous histology. With median follow-up of 96.3 months (for patients still alive), overall survival was identical (hazard ratio 1.03 (0.79-1.34), NS): five-year survival 17% in both arms. The incidence of late grade 3-5 toxicities was 16% in the AM arm and 19% in the control arm (hazard ratio 1.24 (0.66-2.32), NS). There was no significant difference between the arms regarding overall survival, disease-free survival or long-term toxicity.

Conclusion: The chemoradiation regimen of carboplatin and paclitaxel produced long-term results in the multi-institutional setting comparable to other regimens. Amifostine did not appear to compromise survival. As done in RTOG 9801, more consistent reporting of long term toxicity is needed for comparison of different chemoradiation regimens.

Trial registration: ClinicalTrials.gov NCT00003313.

Figure 1

CONSORT flow diagram

Figure 2

(a) Disease-Free Survival, hazard ratio between the arms: 1.07, confidence interval (0.82, 1.38) p=0.64 (b) Overall Survival, hazard ratio between the arms: 1.03, confidence interval (0.79, 1.34) p=0.85 (c) Time to Progression, hazard ratio between the arms: 0.98, confidence interval (0.72, 1.32) p=0.88 (d) Cumulative Severe Toxicity (>= grade 3), hazard ratio between the arms: 1.24, confidence interval (0.66, 2.32) p=0.51. Overall survival and disease-free survival hazard ratios from Cox proportional hazards model; hazard ratios for time to progression and toxicity from Fine-Gray proportional hazards model.