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.