Akira Inoue1, Shunichi Sugawara2, Makoto Maemondo3, Yoshiaki Mori4, Satoshi Oizumi5, Masao Harada6, Kageaki Taima7, Naoto Morikawa8, Takashi Ishida9, Ichiro Kinoshita10, Hiroshi Watanabe11, Toshiro Suzuki12, Taku Nakagawa13, Ryota Saito14, Toshihiro Nukiwa14. 1. Department of Palliative Medicine, Tohoku University School of Medicine, 1-1, Seiryocho, Aobaku, Sendai 980-8574, Japan. Electronic address: akinoue@idac.tohoku.ac.jp. 2. Department of Pulmonary Medicine, Sendai Kousei Hospital, Sendai, Japan. 3. Department of Respiratory Medicine, Miyagi Cancer Center, Natori, Japan. 4. Department of Respiratory Medicine, Iwate Prefectural Central Hospital, Morioka, Japan. 5. First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan. 6. Department of Respiratory Medicine, Hokkaido Cancer Center, Sapporo, Japan. 7. Department of Respiratory Medicine, Hirosaki University, Hirosaki, Japan. 8. Divison of Pulmonary Medicine, Allergy, and Rheumatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Morioka, Japan. 9. Department of Pulmonary Medicine, Fukushima Medical University Hospital, Fukushima, Japan. 10. Department of Medical Oncology, Hokkaido University School of Medicine, Sapporo, Japan. 11. Department of Respiratory Medicine, Saka General Hospital, Shiogama, Japan. 12. Department of Respiratory Medicine, Isawa Hospital, Oshu, Japan. 13. Department of Thoracic Surgery, Omagari Kosei Medical Center, Daisen, Japan. 14. Department of Palliative Medicine, Tohoku University School of Medicine, 1-1, Seiryocho, Aobaku, Sendai 980-8574, Japan.
Abstract
PURPOSE: Amrubicin and re-challenge of platinum doublet are both effective treatments for sensitive-relapsed small-cell lung cancer (SCLC). However, no comparative study of these treatments has been reported. This randomized study was conducted to select the most suitable regimen for future evaluation. PATIENTS AND METHODS: SCLC patients who had relapsed more than 90 days after their first-line platinum-doublet regimen were randomized to receive amrubicin (40mg/m(2), days 1-3) or re-challenge with platinum doublet. Primary endpoint was objective response rate (ORR), with secondary endpoints of progression-free survival (PFS), overall survival and toxicity profiles. We assumed that an ORR of 50% indicates potential usefulness, while that of 30% would constitute the lower limit of interest (alpha 0.1; beta 0.1). Initial estimated accrual was 28 patients to each arm. RESULTS:From February 2008 to June 2013, 60 patients were enrolled and 57 patients (27 amrubicin and 30 re-challenge) were found to be evaluable for efficacy and safety. The ORR and PFS were 67% (90% confidence interval, 52-82) and 5.4 months in the amrubicin group, and 43% (90% confidence interval, 28-58) and 5.1 months in the re-challenge group, respectively. Although grade 3 febrile neutropenia was observed in 19% of patients in the amrubicin group, these episodes were transient and manageable. Non-hematological toxicities were generally moderate and no treatment-related death was observed in either group. CONCLUSION: Only amrubicin met the primary endpoint. Moreover, amrubicin demonstrated superior efficacy over re-challenge of platinum with acceptable levels of toxicity. Further evaluation of amrubicin for sensitive-relapsed SCLC is warranted.
RCT Entities:
PURPOSE:Amrubicin and re-challenge of platinum doublet are both effective treatments for sensitive-relapsed small-cell lung cancer (SCLC). However, no comparative study of these treatments has been reported. This randomized study was conducted to select the most suitable regimen for future evaluation. PATIENTS AND METHODS: SCLCpatients who had relapsed more than 90 days after their first-line platinum-doublet regimen were randomized to receive amrubicin (40mg/m(2), days 1-3) or re-challenge with platinum doublet. Primary endpoint was objective response rate (ORR), with secondary endpoints of progression-free survival (PFS), overall survival and toxicity profiles. We assumed that an ORR of 50% indicates potential usefulness, while that of 30% would constitute the lower limit of interest (alpha 0.1; beta 0.1). Initial estimated accrual was 28 patients to each arm. RESULTS: From February 2008 to June 2013, 60 patients were enrolled and 57 patients (27 amrubicin and 30 re-challenge) were found to be evaluable for efficacy and safety. The ORR and PFS were 67% (90% confidence interval, 52-82) and 5.4 months in the amrubicin group, and 43% (90% confidence interval, 28-58) and 5.1 months in the re-challenge group, respectively. Although grade 3 febrile neutropenia was observed in 19% of patients in the amrubicin group, these episodes were transient and manageable. Non-hematological toxicities were generally moderate and no treatment-related death was observed in either group. CONCLUSION: Only amrubicin met the primary endpoint. Moreover, amrubicin demonstrated superior efficacy over re-challenge of platinum with acceptable levels of toxicity. Further evaluation of amrubicin for sensitive-relapsed SCLC is warranted.