PURPOSE: This multicenter, phase II study was conducted to evaluate the activity of amrubicin, a topoisomerase II inhibitor, against refractory or relapsed small-cell lung cancer (SCLC). PATIENTS AND METHODS: SCLC patients with measurable disease who had been treated previously with at least one platinum-based chemotherapy regimen and had an Eastern Cooperative Oncology Group performance status of 0 to 2 were eligible. Two groups of patients were selected: patients who experienced first-line treatment failure less than 60 days from treatment discontinuation (refractory group), and patients who responded to first-line treatment and experienced disease progression > or = 60 days after treatment discontinuation (sensitive group). Amrubicin was administered as a 5-minute daily intravenous injection at a dose of 40 mg/m2 for 3 consecutive days, every 3 weeks. RESULTS: Between June 2003 and December 2004, 60 patients (16 refractory and 44 sensitive) were enrolled. The median number of treatment cycles was four (range, one to eight). Grade 3 or 4 hematologic toxicities comprised neutropenia (83%), thrombocytopenia (20%), and anemia (33%). Febrile neutropenia was observed in three patients (5%). Nonhematologic toxicities were mild. No treatment-related death was observed. The overall response rates were 50% (95% CI, 25% to 75%) in the refractory group, and 52% (95% CI, 37% to 68%) in the sensitive group. The progression-free survival, overall survival, and 1-year survival in the refractory group and the sensitive group were 2.6 and 4.2 months, 10.3 and 11.6 months, and 40% and 46%, respectively. CONCLUSION: Amrubicin exhibits significant activity against SCLC, with predictable and manageable toxicities; this agent deserves to be studied more extensively in additional trials.
PURPOSE: This multicenter, phase II study was conducted to evaluate the activity of amrubicin, a topoisomerase II inhibitor, against refractory or relapsed small-cell lung cancer (SCLC). PATIENTS AND METHODS: SCLCpatients with measurable disease who had been treated previously with at least one platinum-based chemotherapy regimen and had an Eastern Cooperative Oncology Group performance status of 0 to 2 were eligible. Two groups of patients were selected: patients who experienced first-line treatment failure less than 60 days from treatment discontinuation (refractory group), and patients who responded to first-line treatment and experienced disease progression > or = 60 days after treatment discontinuation (sensitive group). Amrubicin was administered as a 5-minute daily intravenous injection at a dose of 40 mg/m2 for 3 consecutive days, every 3 weeks. RESULTS: Between June 2003 and December 2004, 60 patients (16 refractory and 44 sensitive) were enrolled. The median number of treatment cycles was four (range, one to eight). Grade 3 or 4 hematologic toxicities comprised neutropenia (83%), thrombocytopenia (20%), and anemia (33%). Febrile neutropenia was observed in three patients (5%). Nonhematologic toxicities were mild. No treatment-related death was observed. The overall response rates were 50% (95% CI, 25% to 75%) in the refractory group, and 52% (95% CI, 37% to 68%) in the sensitive group. The progression-free survival, overall survival, and 1-year survival in the refractory group and the sensitive group were 2.6 and 4.2 months, 10.3 and 11.6 months, and 40% and 46%, respectively. CONCLUSION:Amrubicin exhibits significant activity against SCLC, with predictable and manageable toxicities; this agent deserves to be studied more extensively in additional trials.
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