title: S-1 and Cisplatin With or Without Nimotuzumab for Patients With Untreated Unresectable or Metastatic Gastric Cancer: A Randomized, Open-Label Phase 2 Trial.
abstract: This open-label, randomized phase II trial was performed to compare the efficacy and safety of nimotuzumab plus S-1 and cisplatin (NCS) versus S-1 and cisplatin (CS) alone in patients with untreated unresectable or metastatic gastric cancer in the first-line setting. Eligible participants were randomly assigned (1:1) to receive either NCS or CS. The treatment consisted of 3-week cycles of twice-daily S-1 40 mg/m² (on days 1-14) and intravenous cisplatin 30 mg/m² (on days 1, 2), with or without weekly nimotuzumab (200 mg/m²). The primary endpoint was objective response rate (ORR). The second endpoint included progression-free survival (PFS), overall survival (OS), safety and association between efficacy and tumor epidermal growth factor receptor (EGFR) expression. Between October, 2009, and February, 2012, we enrolled 62 patients in Cancer Hospital Chinese Academy of Medical Sciences (CAMS). The ORR for 31 patients allocated NCS was 54.8% compared with 58.1% for 31 patients who were allocated to receive CS alone (P = 0.798). Median PFS for patients in CS arm was significantly improved than that in NCS arm [7.2 months vs. 4.8 months HR = 2.136 (95% CI 1.193-3.826), P = 0.011]. There was also a trend toward better overall survival for patients in CS arm compared with NCS arm [14.3 months vs. 10.2 months; HR = 1.776 (95% CI 0.972-3.246), P = 0.062]. In the EGFR 2+/3+ subgroup, adding nimotuzumab also failed to show additional benefit than chemotherapy alone. Both groups were well tolerated. Less than 10% of patients in both arms developed grade 3/4 toxicity. Combination of nimotuzumab and S-1-cisplatin provided no additional benefit than chemotherapy alone in the first-line treatment of unresectable or metastatic gastric cancer.
authors.affiliation: From the Department of Medical Oncology (FD, ZJ, YS, YS, LY, JZ, JW, YC); The Department of Abdominal Surgical Oncology (ZZ, XY); and Department of Pathology, Cancer Hospital Chinese Academy of Medical Sciences, Beijing, China (SSS).
authors.forename: Feng
authors.initials: F
authors.lastname: Du
authors.forename: Zhaoxu
authors.initials: Z
authors.lastname: Zheng
authors.forename: SuSheng
authors.initials: S
authors.lastname: Shi
authors.forename: Zhichao
authors.initials: Z
authors.lastname: Jiang
authors.forename: Tao
authors.initials: T
authors.lastname: Qu
authors.forename: Xinhua
authors.initials: X
authors.lastname: Yuan
authors.forename: Yongkun
authors.initials: Y
authors.lastname: Sun
authors.forename: Yan
authors.initials: Y
authors.lastname: Song
authors.forename: Lin
authors.initials: L
authors.lastname: Yang
authors.forename: Jiuda
authors.initials: J
authors.lastname: Zhao
authors.forename: Jinwan
authors.initials: J
authors.lastname: Wang
authors.forename: Yihebali
authors.initials: Y
authors.lastname: Chi
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002945:Cisplatin / Q000008:administration & dosage*; D018572:Disease-Free Survival; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage*; D011446:Prospective Studies; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D005641:Tegafur / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; C501466:nimotuzumab; D002945:Cisplatin