Naoto Morikawa1, Akira Inoue2, Shunichi Sugawara3, Makoto Maemondo4, Toshiyuki Harada5, Masao Harada6, Yuka Fujita7, Terufumi Katoh8, Hiroshi Yokouchi9, Hiroshi Watanabe10, Kazuhiro Usui11, Toshiro Suzuki12, Jun Sakakibara-Konishi13, Hiroki Nagai14, Mariko Kanbe15, Toshihiro Nukiwa16. 1. Iwate Medical University School of Medicine, 9-1, Uchimaru, Morioka, Iwate, 020-8505, Japan. Electronic address: carcinoma@nifty.com. 2. Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan. Electronic address: akira.inoue.b2@tohoku.ac.jp. 3. Sendai Kosei Hospital, 4-15, Hirosemachi, Sendai-shi Aoba-ku, Miyagi, 980-0873, Japan. Electronic address: swara357@sendai-kousei-hospital.jp. 4. Miyagi Cancer Center, 47-1 Unodayama, Aijimashiode, Natori, Miyagi 981-1293, Japan. Electronic address: maemondo-ma693@miyagi-pho.jp. 5. Japan Community Health Care Organization Hokkaido Hospital, 8-3-18, 1jo, Nakanoshima, Kotohira, Sapporo, Hokkaido, 062-8618, Japan. Electronic address: harada-toshiyuki@hokkaido.jcho.go.jp. 6. Hokkaido Cancer Center, 2-3-54, 4jo, Kikusui, Shiraishi, Sapporo, Hokkaido, 003-0804, Japan. Electronic address: mharada@sap-cc.go.jp. 7. Asahikawa Medical Center, 7-4048, Hanasakicho, Asahikawa, Hokkaido, 070-8644, Japan. Electronic address: yuka@asahikawamc.hosp.go.jp. 8. Kanagawa Cancer Center, 2-3-2, Nakao, Asahi, Yokohama, Kanagawa, 241-8514, Japan. Electronic address: t-kato@kanagawa-junko.jp. 9. Fukushima Medical University, 1Hikariga-oka, Fukushima, 960-1295, Japan. Electronic address: hyokouch@gmail.com. 10. Saka General Hospital, 16-5, Nishikicho, Shiogama, Miyagi, 985-0024, Japan. Electronic address: nabe14627@yahoo.co.jp. 11. NTT Medical Center Tokyo, 5-9-22, Higashigotanda, Shinagawa, Tokyo, 141-8625, Japan. Electronic address: usui@east.ntt.co.jp. 12. Iwate Prefectural Isawa Hospital, 61, Ryugababa, Mizusawa, Oshu, Iwate, 023-0864, Japan. Electronic address: toshi@isawa-hosp.mizusawa.iwate.jp. 13. Hokkaido University, Kita 8, Nishi 5, Kita-ku, Sapporo, Hokkaido, 060-0808, Japan. Electronic address: konishj@med.hokudai.ac.jp. 14. Kyoto University, Yoshida-honmachi, Sakyo-ku, Kyoto 606-8501, Japan. Electronic address: hwithe@kuhp.kyoto-u.ac.jp. 15. Senseki Hospital, 53-7, Akai-aza-dai, Higashimatsushima, Miyagi, 981-0501, Japan. Electronic address: m-kambe@senseki.gr.jp. 16. Japan Anti-Tuberculosis Association, 3-1-24 Matsuyama, Kiyose-shi, Tokyo, 204-8533, Japan. Electronic address: toshinkw47@gmail.com.
Abstract
OBJECTIVE:Carboplatin-based regimens are the standard regimens for patients with extensive-stage small-cell lung cancer (ES-SCLC). However, the efficacies of these regimens are unsatisfactory. We previously identified carboplatin plus irinotecan (CI) and carboplatin plus amrubicin (CA) as promising new carboplatin-based regimens. Accordingly, we conducted a randomized phase II study to identify the appropriate regimen for future phase III trials. MATERIALS AND METHODS:Chemotherapy-naïve patients with ES-SCLC were randomly assigned to receive 4-6 cycles of carboplatin [area under the curve (AUC) 5.0, day 1] plus irinotecan (70mg/m2, days 1 and 8) every 3 weeks (CI arm) or carboplatin (AUC 4.0, day 1) plus amrubicin (35mg/m2, days 1-3) every 3 weeks (CA arm). The primary endpoint was the overall response rate (ORR). The secondary endpoints were the progression-free survival (PFS), overall survival (OS) and toxicity. RESULTS:Between December 2009 and March 2013, 71 patients were enrolled. One patient in each arm did not receive any protocol treatment due to rapid disease progression. The characteristics of the treated patients were as follows: median age, 70 years (range 51-84 years); proportion of males, 84%. The ORRs were 79% and 89% in the CI and CA arms, respectively. The median PFS values were 5.1 and 6.2 months in the CI and CA arms, respectively [CA; hazard ratio (HR)=0.59, 95% confidence interval (CI): 0.35-0.98, P=0.042]. The grade 3 or higher toxicity severities were neutropenia (CI, 53% and CA, 89%), anemia (CI, 26% and CA, 20%), thrombocytopenia (CI, 18% and CA, 14%), and febrile neutropenia (CI, 12% and CA, 29%). No treatment-related deaths were observed. CONCLUSION:CA was numerically more effective than CI, with acceptable toxicity, in chemo-naïve ES-SCLC patients. CA could be selected for future phase III trials.
RCT Entities:
OBJECTIVE:Carboplatin-based regimens are the standard regimens for patients with extensive-stage small-cell lung cancer (ES-SCLC). However, the efficacies of these regimens are unsatisfactory. We previously identified carboplatin plus irinotecan (CI) and carboplatin plus amrubicin (CA) as promising new carboplatin-based regimens. Accordingly, we conducted a randomized phase II study to identify the appropriate regimen for future phase III trials. MATERIALS AND METHODS: Chemotherapy-naïve patients with ES-SCLC were randomly assigned to receive 4-6 cycles of carboplatin [area under the curve (AUC) 5.0, day 1] plus irinotecan (70mg/m2, days 1 and 8) every 3 weeks (CI arm) or carboplatin (AUC 4.0, day 1) plus amrubicin (35mg/m2, days 1-3) every 3 weeks (CA arm). The primary endpoint was the overall response rate (ORR). The secondary endpoints were the progression-free survival (PFS), overall survival (OS) and toxicity. RESULTS: Between December 2009 and March 2013, 71 patients were enrolled. One patient in each arm did not receive any protocol treatment due to rapid disease progression. The characteristics of the treated patients were as follows: median age, 70 years (range 51-84 years); proportion of males, 84%. The ORRs were 79% and 89% in the CI and CA arms, respectively. The median PFS values were 5.1 and 6.2 months in the CI and CA arms, respectively [CA; hazard ratio (HR)=0.59, 95% confidence interval (CI): 0.35-0.98, P=0.042]. The grade 3 or higher toxicity severities were neutropenia (CI, 53% and CA, 89%), anemia (CI, 26% and CA, 20%), thrombocytopenia (CI, 18% and CA, 14%), and febrile neutropenia (CI, 12% and CA, 29%). No treatment-related deaths were observed. CONCLUSION: CA was numerically more effective than CI, with acceptable toxicity, in chemo-naïve ES-SCLCpatients. CA could be selected for future phase III trials.