Phase III double-blind, placebo-controlled study of thalidomide in extensive-disease small-cell lung cancer after response to chemotherapy:: An intergroup study FNCLCC cleo04-IFCT 00-01

Purpose This randomized, double-blind, placebo-controlled phase III study aimed to determine whether thalidomide prolongs survival of patients with extensive- disease small- cell lung cancer ( SCLC). Patients and Methods One hundred nineteen patients received two courses of etoposide, cisplatin, cyclophosphamide, and 4'- epidoxorubicin ( PCDE). Responder patients who had recovered from chemotherapy toxicity were randomly assigned to receive four additional PCDE cycles plus thalidomide ( 400 mg daily) or placebo. Results After the first two PCDE cycles, objective response rate was 81.5%, and 92 patients were randomly assigned to placebo ( n = 43) or thalidomide ( n = 49). Median exposure duration to placebo was 4.5 months, and median exposure to thalidomide was 4.9 months. Patients treated with thalidomide had a longer survival compared with patients who received placebo, although the difference was not statistically significant ( minimal follow-up, 3 years; median survival time, 11.7 v 8.7 months, respectively; log- rank test: hazard ratio [ HR] = 0.74; 95% CI, 0.49 to 1.12; P =.16). Patients with a performance status ( PS) of 1 or 2 who received thalidomide had a significantly longer survival ( HR = 0.59; 95% CI, 0.37 to 0.92; P =.02). The disease also progressed slower in patients with PS of 1 or 2 receiving thalidomide ( HR = 0.54; 95% CI, 0.36 to 0.87; P =.02), whereas the difference did not reach statistical significance for the whole population ( HR = 0.74; 95% CI, 0.49 to 1.12; P =.15). Neuropathy occurred more frequently in the thalidomide group compared with the placebo group ( 33% v 12%, respectively). Conclusion Treatment with thalidomide was not associated with a significant improvement in survival of SCLC patients. There was pronounced heterogeneity in survival outcomes between groups of patients. Some benefit was observed among patients with a PS of 1 or 2 ( exploratory analyses), deserving further studies targeting angiogenesis in this disease.