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 receivedthalidomide 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.
RCT Entities:
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 SCLCpatients. 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.
Authors: Paul A Bunn; John D Minna; Alexander Augustyn; Adi F Gazdar; Youcef Ouadah; Mark A Krasnow; Anton Berns; Elisabeth Brambilla; Natasha Rekhtman; Pierre P Massion; Matthew Niederst; Martin Peifer; Jun Yokota; Ramaswamy Govindan; John T Poirier; Lauren A Byers; Murry W Wynes; David G McFadden; David MacPherson; Christine L Hann; Anna F Farago; Caroline Dive; Beverly A Teicher; Craig D Peacock; Jane E Johnson; Melanie H Cobb; Hans-Guido Wendel; David Spigel; Julien Sage; Ping Yang; M Catherine Pietanza; Lee M Krug; John Heymach; Peter Ujhazy; Caicun Zhou; Koichi Goto; Afshin Dowlati; Camilla Laulund Christensen; Keunchil Park; Lawrence H Einhorn; Martin J Edelman; Giuseppe Giaccone; David E Gerber; Ravi Salgia; Taofeek Owonikoko; Shakun Malik; Niki Karachaliou; David R Gandara; Ben J Slotman; Fiona Blackhall; Glenwood Goss; Roman Thomas; Charles M Rudin; Fred R Hirsch Journal: J Thorac Oncol Date: 2016-01-30 Impact factor: 15.609
Authors: Tien Hoang; Suzanne E Dahlberg; Joan H Schiller; Minesh P Mehta; Thomas J Fitzgerald; Steven A Belinsky; David H Johnson Journal: J Clin Oncol Date: 2012-01-23 Impact factor: 44.544
Authors: Stefan Hoschek; Ursula Hoschek-Risslegger; Michael Fiegl; August Zabernigg; Georg Pall; Thomas Auberger; Eberhard Gunsilius; Thomas Schmid; Herbert Jamnig; Wolfgang Hilbe Journal: Wien Klin Wochenschr Date: 2007 Impact factor: 1.704