title: Randomised phase III trial of second-line irinotecan plus cisplatin versus irinotecan alone in patients with advanced gastric cancer refractory to S-1 monotherapy: TRICS trial.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  No survival benefit was observed upon adding CDDP to CPT-11 after S-1 monotherapy failure.
authors: Department of Surgery, Osaka National Hospital, 2-1-14, Houenzaka, Chuo-ku, Osaka 540-0006, Japan. Electronic address: kazuno13@hotmail.co.jp.
authors: Kazuhiro
authors: K
authors: Nishikawa
authors: Department of Surgery, Osaka General Medical Center, 3-1-56, Bandaihigashi, Sumiyoshi-ku, Osaka 558-0056, Japan. Electronic address: fujitani@gh.opho.jp.
authors: Kazumasa
authors: K
authors: Fujitani
authors: Department of Surgery, Gifu Central Hospital, 3-25, Kawabe, Gifu 501-1151, Japan. Electronic address: hinagaki@skhosp.or.jp.
authors: Hitoshi
authors: H
authors: Inagaki
authors: 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.
authors: Yusuke
authors: Y
authors: Akamaru
authors: 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.
authors: Shinya
authors: S
authors: Tokunaga
authors: Department of Surgery, Shizuoka General Hospital, 4-27-1, Kitaando, Aoi-ku, Shizuoka 420-0881, Japan. Electronic address: masakazu-takagi@i.shizuoka-pho.jp.
authors: Masakazu
authors: M
authors: Takagi
authors: Department of Surgery, Kansai Rosai Hospital, 3-1-69, Inabaso, Amagasaki 537-0025, Japan. Electronic address: stamura@kanrou.net.
authors: Shigeyuki
authors: S
authors: Tamura
authors: 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.
authors: Naotoshi
authors: N
authors: Sugimoto
authors: Department of Gastroenterology, Saiseikai Shiga Prefectural Hospital, 2-4-1, Ohashi, Ritto 520-3046, Japan. Electronic address: bssjh242@yahoo.co.jp.
authors: Tadashi
authors: T
authors: Shigematsu
authors: Department of Gastrointestinal Surgery, Kanagawa Cancer Center, 2-3-2, Nakao, Asahi-ku, Yokohama 241-0815, Japan. Electronic address: yoshikawat@kcch.jp.
authors: Takaki
authors: T
authors: Yoshikawa
authors: Department of Digestive Tract and General Surgery, Saitama Medical Center, 1981, Kamoda, Kawagoe 350-0844, Japan. Electronic address: itoru@saitama-med.ac.jp.
authors: Tohru
authors: T
authors: Ishiguro
authors: Comprehensive Cancer Center, Aizawa Hospital, 2-5-1, Honjo, Matsumoto 390-0814, Japan. Electronic address: geka-dr7@ai-hosp.or.jp.
authors: Masato
authors: M
authors: Nakamura
authors: 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.
authors: Satoshi
authors: S
authors: Morita
authors: Date Center, Epidemiological & Clinical Research Information Network, 21-7, Shogoinsannocho, Sakyo-ku, Kyoto 606-8392, Japan. Electronic address: miya@ecrin.or.jp.
authors: Yumi
authors: Y
authors: Miyashita
authors: Department of Gastroenterological Center, Yokohama City University Medical Center, 4-57, Urafunecho, Minami-ku, Yokohama 232-0024, Japan. Electronic address: tuburayaa@gmail.com.
authors: Akira
authors: A
authors: Tsuburaya
authors: Tokai Central Hospital, 4-6-2, Higashijimacho Sohara, Kakamigahara 504-8601, Japan. Electronic address: sakamjun@tokaihp.jp.
authors: Junichi
authors: J
authors: Sakamoto
authors: Kaizuka City Hospital, 3-10-20, Hori, Kaizuka 597-0015, Japan. Electronic address: tsujinaka@hosp.kaizuka.osaka.jp.
authors: Toshimasa
authors: T
authors: Tsujinaka
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects; D018450:Disease Progression; D004338:Drug Combinations; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D010094:Oxonic Acid / Q000627:therapeutic use*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D005641:Tegafur / Q000627:therapeutic use*; D017211:Treatment Failure
chemical_list: D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D000077146:Irinotecan; D002945:Cisplatin; D002166:Camptothecin
keywords: Cisplatin; Combination chemotherapy; Fluoropyrimidine; Gastric cancer; Irinotecan; Phase III; S-1; Second-line