Kazuhiro Nishikawa1, Kazumasa Fujitani2, Hitoshi Inagaki3, Yusuke Akamaru4, Shinya Tokunaga5, Masakazu Takagi6, Shigeyuki Tamura7, Naotoshi Sugimoto8, Tadashi Shigematsu9, Takaki Yoshikawa10, Tohru Ishiguro11, Masato Nakamura12, Satoshi Morita13, Yumi Miyashita14, Akira Tsuburaya15, Junichi Sakamoto16, Toshimasa Tsujinaka17. 1. Department of Surgery, Osaka National Hospital, 2-1-14, Houenzaka, Chuo-ku, Osaka 540-0006, Japan. Electronic address: kazuno13@hotmail.co.jp. 2. Department of Surgery, Osaka General Medical Center, 3-1-56, Bandaihigashi, Sumiyoshi-ku, Osaka 558-0056, Japan. Electronic address: fujitani@gh.opho.jp. 3. Department of Surgery, Gifu Central Hospital, 3-25, Kawabe, Gifu 501-1151, Japan. Electronic address: hinagaki@skhosp.or.jp. 4. Department of Surgery, Osaka Kose-Nenkin Hospital, 4-2-78, Fukushima, Fukushima-ku, Osaka 553-0007, Japan. Electronic address: akamaru@ka3.so-net.ne.jp. 5. Department of Clinical Oncology, Osaka City General Hospital, 2-13-22, Miyakojimahondori, Miyakojima-ku, Osaka 534-0021, Japan. Electronic address: s-tokunaga@hospital.city.osaka.jp. 6. Department of Surgery, Shizuoka General Hospital, 4-27-1, Kitaando, Aoi-ku, Shizuoka 420-0881, Japan. Electronic address: masakazu-takagi@i.shizuoka-pho.jp. 7. Department of Surgery, Kansai Rosai Hospital, 3-1-69, Inabaso, Amagasaki 537-0025, Japan. Electronic address: stamura@kanrou.net. 8. Department of Clinical Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3, Nakamichi, Higashinari-ku, Osaka 537-0025, Japan. Electronic address: sugimoto-na2@mc.pref.osaka.jp. 9. Department of Gastroenterology, Saiseikai Shiga Prefectural Hospital, 2-4-1, Ohashi, Ritto 520-3046, Japan. Electronic address: bssjh242@yahoo.co.jp. 10. Department of Gastrointestinal Surgery, Kanagawa Cancer Center, 2-3-2, Nakao, Asahi-ku, Yokohama 241-0815, Japan. Electronic address: yoshikawat@kcch.jp. 11. Department of Digestive Tract and General Surgery, Saitama Medical Center, 1981, Kamoda, Kawagoe 350-0844, Japan. Electronic address: itoru@saitama-med.ac.jp. 12. Comprehensive Cancer Center, Aizawa Hospital, 2-5-1, Honjo, Matsumoto 390-0814, Japan. Electronic address: geka-dr7@ai-hosp.or.jp. 13. Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, 54, Shogoinkawaharacho, Sakyo-ku, Kyoto 606-8397, Japan. Electronic address: smorita@kuhp.kyoto-u.ac.jp. 14. Date Center, Epidemiological & Clinical Research Information Network, 21-7, Shogoinsannocho, Sakyo-ku, Kyoto 606-8392, Japan. Electronic address: miya@ecrin.or.jp. 15. Department of Gastroenterological Center, Yokohama City University Medical Center, 4-57, Urafunecho, Minami-ku, Yokohama 232-0024, Japan. Electronic address: tuburayaa@gmail.com. 16. Tokai Central Hospital, 4-6-2, Higashijimacho Sohara, Kakamigahara 504-8601, Japan. Electronic address: sakamjun@tokaihp.jp. 17. Kaizuka City Hospital, 3-10-20, Hori, Kaizuka 597-0015, Japan. Electronic address: tsujinaka@hosp.kaizuka.osaka.jp.
Abstract
AIM: The optimal second-line regimen for treating advanced gastric cancer (AGC) remains unclear. While irinotecan (CPT-11) plus cisplatin (CDDP) combination therapy and CPT-11 monotherapy have been explored in the second-line setting, the superiority of second-line platinum-based therapies for AGC patients initially treated with S-1 monotherapy has not yet been evaluated; therefore, we aimed to examine the survival benefit of CPT-11/CDDP combination over CPT-11 monotherapy. METHODS:AGC patients showing progression after S-1 monotherapy for advanced cancer or recurrence within 6 months after completion of S-1 adjuvant therapy were randomly allocated to CPT-11/CDDP (CPT-11, 60 mg/m(2); CDDP, 30 mg/m(2), q2w) or CPT-11 (150 mg/m(2), q2w). RESULTS:Sixty-eight advanced and95 recurrent cases were evaluated. The median overall survivals were 13.9 (95% confidence interval [CI]: 10.8-17.6) and 12.7 (95% CI: 10.3-17.2) months for CPT-11/CDDP and CPT-11, respectively (hazard ratio: 0.834; 95% CI: 0.596-1.167, P = 0.288). No significant differences were observed in the secondary end-points, including progression-free survival (4.6 [95% CI: 3.4-5.9] versus 4.1 [95% CI: 3.3-4.9]months) and response rate (16.9% [95% CI: 8.8-28.3] versus 15.4% [95% CI: 7.6-26.5]). The incidences of grade 3-4 anaemia (16% versus 4%) and elevated serum lactate dehydrogenase levels (5% versus 0%) were higher for CPT-11/CDDP than for CPT-11. Exploratory subgroup analysis revealed that CPT-11/CDDP was significantly more effective for intestinal-type AGC, compared with CPT-11 (overall survival: 15.8 versus 14.0 months; P = 0.019). CONCLUSION: No survival benefit was observed upon adding CDDP to CPT-11 after S-1 monotherapy failure.
RCT Entities:
AIM: The optimal second-line regimen for treating advanced gastric cancer (AGC) remains unclear. While irinotecan (CPT-11) plus cisplatin (CDDP) combination therapy and CPT-11 monotherapy have been explored in the second-line setting, the superiority of second-line platinum-based therapies for AGC patients initially treated with S-1 monotherapy has not yet been evaluated; therefore, we aimed to examine the survival benefit of CPT-11/CDDP combination over CPT-11 monotherapy. METHODS: AGC patients showing progression after S-1 monotherapy for advanced cancer or recurrence within 6 months after completion of S-1 adjuvant therapy were randomly allocated to CPT-11/CDDP (CPT-11, 60 mg/m(2); CDDP, 30 mg/m(2), q2w) or CPT-11 (150 mg/m(2), q2w). RESULTS: Sixty-eight advanced and 95 recurrent cases were evaluated. The median overall survivals were 13.9 (95% confidence interval [CI]: 10.8-17.6) and 12.7 (95% CI: 10.3-17.2) months for CPT-11/CDDP and CPT-11, respectively (hazard ratio: 0.834; 95% CI: 0.596-1.167, P = 0.288). No significant differences were observed in the secondary end-points, including progression-free survival (4.6 [95% CI: 3.4-5.9] versus 4.1 [95% CI: 3.3-4.9]months) and response rate (16.9% [95% CI: 8.8-28.3] versus 15.4% [95% CI: 7.6-26.5]). The incidences of grade 3-4 anaemia (16% versus 4%) and elevated serum lactate dehydrogenase levels (5% versus 0%) were higher for CPT-11/CDDP than for CPT-11. Exploratory subgroup analysis revealed that CPT-11/CDDP was significantly more effective for intestinal-type AGC, compared with CPT-11 (overall survival: 15.8 versus 14.0 months; P = 0.019). CONCLUSION: No survival benefit was observed upon adding CDDP to CPT-11 after S-1 monotherapy failure.