Randomized phase III study of thoracic radiation in combination with paclitaxel and carboplatin with or without thalidomide in patients with stage III non-small-cell lung cancer: The ECOG 3598 study

Purpose: The primary objective of this study was to compare the survival of patients with unresectable stage III non-small-cell lung cancer (NSCLC) treated with combined chemoradiotherapy with or without thalidomide. Patients and Methods: Patients were randomly assigned to the control arm (PC) involving two cycles of induction paclitaxel 225 mg/m ² and carboplatin area under the curve (AUC) 6 followed by 60 Gy thoracic radiation administered concurrently with weekly paclitaxel 45 mg/m ² and carboplatin AUC 2, or to the experimental arm (TPC), receiving the same treatment in combination with thalidomide at a starting dose of 200 mg daily. The protocol allowed an increase in thalidomide dose up to 1,000 mg daily based on patient tolerability. Results: A total of 546 patients were eligible, including 275 in the PC arm and 271 in the TPC arm. Median overall survival, progression-free survival, and overall response rate were 15.3 months, 7.4 months, and 35.0%, respectively, for patients in the PC arm, in comparison with 16.0 months (P = .99), 7.8 months (P = .96), and 38.2% (P = .47), respectively, for patients in the TPC arm. Overall, there was higher incidence of grade 3 toxicities in patients treated with thalidomide. Several grade 3 or higher events were observed more often in the TPC arm, including thromboembolism, fatigue, depressed consciousness, dizziness, sensory neuropathy, tremor, constipation, dyspnea, hypoxia, hypokalemia, rash, and edema. Low-dose aspirin did not reduce the thromboembolic rate. Conclusion: The addition of thalidomide to chemoradiotherapy increased toxicities but did not improve survival in patients with locally advanced NSCLC.