title: Randomized phase II trial of nimotuzumab plus irinotecan versus irinotecan alone as second-line therapy for patients with advanced gastric cancer.
abstract: BACKGROUND
  This multicenter, randomized phase II trial was conducted to compare the efficacy and safety of nimotuzumab plus irinotecan (N-IRI) versus irinotecan alone (IRI) in patients with advanced gastric cancer (AGC) showing disease progression after previous 5-fluorouracil-based therapy.
  
  
  METHODS
  Irinotecan-naive patients (n = 82) received N-IRI (nimotuzumab 400 mg weekly plus irinotecan 150 mg/m(2) biweekly) or IRI (irinotecan 150 mg/m(2) biweekly) until disease progression. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS), response rate (RR), safety, tolerability, and the correlation between efficacy and tumor epidermal growth factor receptor (EGFR) expression.
  
  
  RESULTS
  Of 83 patients, 40 and 43 patients were randomly assigned to the N-IRI and IRI groups, respectively. In the N-IRI/IRI treatment group, median PFS was 73.0/85.0 days (P = 0.5668), and median OS and RR at 18 months were 250.5/232.0 days (P = 0.9778) and 18.4/10.3 %, respectively. Median PFS and OS in the EGFR 2+/3+ subgroups were 118.5/59.0 and 358.5/229.5 days, respectively. The RR was 33.3/0.0 % in the N-IRI/IRI treatment group. The incidence of grade 3 or higher adverse events was 77.5/64.3 %. No adverse events of grade 3 or higher skin rash or grade 3 or higher infusion-related reaction were reported.
  
  
  CONCLUSIONS
  There was no superiority of N-IRI over IRI alone in terms of PFS in 5-fluorouracil-refractory AGC patients. However, N-IRI showed potential improvement in the EGFR 2+/3+ subgroup based on improved RR, PFS, and OS.
authors.affiliation: Medical Oncology, Kinki University Faculty of Medicine, Osaka, Japan.
authors.forename: Taroh
authors.initials: T
authors.lastname: Satoh
authors.affiliation: Hemato-Oncology, Internal Medicine, Yeungnam University Hospital, Daegu, Republic of Korea.
authors.forename: Kyung Hee
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Medical Oncology, Internal Medicine, Yonsei Cancer Center, Yonsei Cancer Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Rha
authors.affiliation: Medical Oncology, Saitama Medical University International Medical Center, Saitama, Japan.
authors.forename: Yasutsuna
authors.initials: Y
authors.lastname: Sasaki
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Sungkyunkwan University Samsung Medical Center, Seoul, Republic of Korea.
authors.forename: Se Hoon
authors.initials: SH
authors.lastname: Park
authors.affiliation: Division of Cancer Chemotherapy, Hokkaido University Hospital, Hokkaido, Japan.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Komatsu
authors.affiliation: Division of GI Oncology, Shizuoka Cancer Center, Shizuoka, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yasui
authors.affiliation: Hematology-Oncology, Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Tae-You
authors.initials: TY
authors.lastname: Kim
authors.affiliation: Department of Gastroenterology, Saitama Cancer Center, Saitama, Japan.
authors.forename: Kensei
authors.initials: K
authors.lastname: Yamaguchi
authors.affiliation: Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan.
authors.forename: Nozomu
authors.initials: N
authors.lastname: Fuse
authors.affiliation: Gastrointestinal Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Yamada
authors.affiliation: Department of Clinical Oncology, Aichi Cancer Center Hospital, Aichi, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ura
authors.affiliation: Department of Medical Oncology and Hematology, Kyung Hee University Hospital, Seoul, Republic of Korea.
authors.forename: Si-Young
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Internal Medicine, Misawa Municipal Hospital, Aomori, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Munakata
authors.affiliation: Medical Oncology and Gastroenterology, Aomori Prefectural Central Hospital, Aomori, Japan.
authors.forename: Soh
authors.initials: S
authors.lastname: Saitoh
authors.affiliation: Department of Genome Biology, Kinki University School of Medicine, Osaka, Japan.
authors.forename: Kazuto
authors.initials: K
authors.lastname: Nishio
authors.affiliation: Department of Biostatics and Epidemiology, Yokohama City University, Kanagawa, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Morita
authors.affiliation: Clinical Development Department II, Daiichi Sankyo Co., Ltd., Tokyo, Japan.
authors.forename: Eriko
authors.initials: E
authors.lastname: Yamamoto
authors.affiliation: Clinical Data and Biostatistics Department, Daiichi Sankyo Co., Ltd., Tokyo, Japan.
authors.forename: Qingwei
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Medical and Regulatory Affairs Department, Kuhnil Pharm. Co., Ltd., Seoul, Republic of Korea.
authors.forename: Jung-mi
authors.initials: JM
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Section of Hemato-Oncology, Korea University Anam Hospital, 126-1 Anam-dong 5ga, Seongbuk-gu, Seoul, 136-705, Republic of Korea. yhk0215@korea.ac.kr.
authors.forename: Yeul Hong
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Internal Medicine, Misawa Municipal Hospital, Aomori, Japan.
authors.forename: Yuh
authors.initials: Y
authors.lastname: Sakata
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D000077146:Irinotecan; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D016133:Polymerase Chain Reaction; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D016879:Salvage Therapy / Q000379:methods; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D002166:Camptothecin; D066246:ErbB Receptors; D000077146:Irinotecan; D018719:Erb-b2 Receptor Tyrosine Kinases; C501466:nimotuzumab; C512478:EGFR protein, human; C508053:ERBB2 protein, human
keywords: Advanced gastric cancer; Anti-EGFR; Irinotecan; Nimotuzumab; Second-line therapy