Yosuke Kawashima1, Akira Inoue2, Shunichi Sugawara3, Satoshi Oizumi4, Makoto Maemondo5, Koichi Okudera6, Toshiro Suzuki7, Kazuhiro Usui8, Masao Harada9, Naoto Morikawa10, Yukihiro Hasegawa11, Ryota Saito12, Osamu Ishimoto13, Tomohiro Sakakibara14, Hajime Asahina15, Toshihiro Nukiwa16. 1. Department of Pulmonary Medicine, Sendai Kousei Hospital, 4-15 Hirose-machi, Aoba-ku, Sendai 980-0873, Japan. Electronic address: yousukekawashima3@yahoo.co.jp. 2. Department of Respiratory Medicine, Tohoku University Hospital, 1-1 Seiryou-machi, Aoba-ku, Sendai 980-8574, Japan. Electronic address: akinoue@idac.tohoku.ac.jp. 3. Department of Pulmonary Medicine, Sendai Kousei Hospital, 4-15 Hirose-machi, Aoba-ku, Sendai 980-0873, Japan. Electronic address: swara357@cat-v.ne.jp. 4. First Department of Medicine, Hokkaido University School of Medicine, Kita 15-jo Nishi 7-chome, Kita-ku, Sapporo 060-8638, Japan. Electronic address: soizumi@med.hokudai.ac.jp. 5. Department of Respiratory Medicine, Miyagi Cancer Center, 47-1 Nodayama, Medeshima-shiote, Natori 981-1293, Japan. Electronic address: maemondo-ma693@miyagi-pho.jp. 6. Department of Respiratory Medicine, Hirosaki Central Hospital, 3-1 Yoshino-machi, Hirosaki 036-8188, Japan. Electronic address: hppokudera@gmail.com. 7. Department of Respiratory Medicine, Isawa Hospital, 61 Ryugababa, Mizusawa-ku, Oshu 023-0864, Japan. Electronic address: toshi@isawa-hosp.mizusawa.iwate.jp. 8. Division of Respirology, NTT Medical Center Tokyo, 5-9-22 Higashi Gotanda, Shinagawa-ku, Tokyo 141-8625, Japan. Electronic address: usui@east.ntt.co.jp. 9. Department of Respiratory Medicine, Hokkaido Cancer Center, 2-3-54 Kikusui 4-jo, Shiroishi-ku, Sapporo 003-0804, Japan. Electronic address: mharada@sap-cc.go.jp. 10. Division of Pulmonary Medicine, Allergy, and Rheumatology, Department of Internal Medicine, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka 020-8505, Japan. Electronic address: carcinoma@nifty.com. 11. Department of Respiratory Medicine, Aomori Prefectural Central Hospital, 2-1-1 Higashitukurimichi, Aomori 030-8553, Japan. Electronic address: yukihiro_hasegawa@med.pref.aomori.jp. 12. Department of Respiratory Medicine, Tohoku University Hospital, 1-1 Seiryou-machi, Aoba-ku, Sendai 980-8574, Japan. Electronic address: beambitious0529@yahoo.co.jp. 13. Department of Pulmonary Medicine, Sendai Kousei Hospital, 4-15 Hirose-machi, Aoba-ku, Sendai 980-0873, Japan. Electronic address: ishimoto@crest.ocn.ne.jp. 14. Department of Respiratory Medicine, Tohoku University Hospital, 1-1 Seiryou-machi, Aoba-ku, Sendai 980-8574, Japan. Electronic address: sakatomo@idac.tohoku.ac.jp. 15. First Department of Medicine, Hokkaido University School of Medicine, Kita 15-jo Nishi 7-chome, Kita-ku, Sapporo 060-8638, Japan. Electronic address: asahinah@huhp.hokudai.ac.jp. 16. South Miyagi Medical Center, 38-1 Nishi, Ogawara, Shibata 989-1253, Japan. Electronic address: toshinkw47@gmail.com.
Abstract
BACKGROUND: Amrubicin (AMR), a new anthracycline agent, has shown promising results for advanced small-cell lung cancer (SCLC), although the efficacy of AMR alone against refractory relapsed SCLC is insufficient. This study was conducted to evaluate the safety and efficacy of the combination of AMR and carboplatin (CBDCA) in patients with refractory relapsed SCLC. METHODS: Patients with advanced SCLC who relapsed within 90 days after the completion of first-line chemotherapy received AMR (30mg/m(2), days 1-3) and CBDCA (area under the curve 4.0mgmL(-1)min(-1), day 1) every 3 weeks. The primary endpoint of this study was the overall response rate (ORR), and the secondary endpoints were progression-free survival (PFS), overall survival, and the toxicity profile. Assuming that an ORR of 45% in eligible patients would indicate potential usefulness and an ORR of 20% would be the lower limit of interest, with α=0.10 and β=0.10, at least 24 patients were required. RESULTS: Among 29 eligible patients, the ORR was 34% (90% confidence interval, 20-48). The median PFS was 3.5 months, whereas the median survival time was 7.3 months. The most common grade 3-4 toxicity was neutropenia (79%), although only one patient (3%) suffered from febrile neutropenia. Non-hematological toxicities were of moderate severity and no treatment-related death was observed. CONCLUSIONS: This is the first prospective study of AMR combined with CBDCA for refractory relapsed SCLC, which was effective and well tolerated. However, further investigation of this regimen is warranted.
BACKGROUND:Amrubicin (AMR), a new anthracycline agent, has shown promising results for advanced small-cell lung cancer (SCLC), although the efficacy of AMR alone against refractory relapsed SCLC is insufficient. This study was conducted to evaluate the safety and efficacy of the combination of AMR and carboplatin (CBDCA) in patients with refractory relapsed SCLC. METHODS:Patients with advanced SCLC who relapsed within 90 days after the completion of first-line chemotherapy received AMR (30mg/m(2), days 1-3) and CBDCA (area under the curve 4.0mgmL(-1)min(-1), day 1) every 3 weeks. The primary endpoint of this study was the overall response rate (ORR), and the secondary endpoints were progression-free survival (PFS), overall survival, and the toxicity profile. Assuming that an ORR of 45% in eligible patients would indicate potential usefulness and an ORR of 20% would be the lower limit of interest, with α=0.10 and β=0.10, at least 24 patients were required. RESULTS: Among 29 eligible patients, the ORR was 34% (90% confidence interval, 20-48). The median PFS was 3.5 months, whereas the median survival time was 7.3 months. The most common grade 3-4 toxicity was neutropenia (79%), although only one patient (3%) suffered from febrile neutropenia. Non-hematological toxicities were of moderate severity and no treatment-related death was observed. CONCLUSIONS: This is the first prospective study of AMR combined with CBDCA for refractory relapsed SCLC, which was effective and well tolerated. However, further investigation of this regimen is warranted.