title: Optimal regimen of trastuzumab in combination with oxaliplatin/ capecitabine in first-line treatment of HER2-positive advanced gastric cancer (CGOG1001): a multicenter, phase II trial.
abstract: BACKGROUND
  The ToGA study showed that trastuzumab plus chemotherapy prolonged median survival in patients with human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer. Among chemotherapy options, oxaliplatin might be as effective as cisplatin but has shown to be more tolerable. To further improve treatment options for patients with advanced gastric cancer, we initiated a study to evaluate the efficacy and safety of trastuzumab plus oxaliplatin/capecitabine in patients with HER2-positive advanced gastric cancer.
  
  
  METHODS
  CGOG1001 was an open-label, multicenter, prospective phase II study. Patients with chemotherapy-naive HER2-positive advanced gastric cancer were eligible. Trastuzumab was administered at a loading dose of 8 mg/kg followed by 6 mg/kg infusion every 3 weeks (q3w). Oxaliplatin was administrated as a 130 mg/m(2) infusion, q3w, for up to 6 cycles. Capecitabine 1000 mg/m(2) was given orally twice daily on days 1-14 followed by a 7-day rest interval. Trastuzumab and capecitabine were continued until disease progression or intolerable toxicity. The primary endpoint was objective response rate. Simon two-stage design (H0 = 40%, H1 = 60%, α = 0.05, β = 0.2) by Response Evaluation Criteria In Solid Tumors 1.0 was applied.
  
  
  RESULTS
  Fifty-one patients were enrolled. Confirmed response was recorded in 46 patients. One patient achieved complete response and 33 patients achieved partial response (response rate 34/51 [66.7%] in the intent-to-treat population). Median follow-up time was 28.6 months, with a median progression-free survival of 9.2 months (95% confidence interval [CI]: 6.5-11.6) and a median overall survival (OS) of 19.5 months (95% CI: 15.5-26.0). Patients with a HER2/CEP17 ratio of greater than five achieved improved OS (20.9 vs 19.5 months, p = 0.001). The most common adverse events of grade 3 or above were thrombocytopenia (21.6%), neutropenia (13.7%), anemia (5.9 %) and leucopenia (3.9%).
  
  
  CONCLUSIONS
  The addition of trastuzumab to oxaliplatin/capecitabine was well tolerated and the results demonstrated encouraging efficacy.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01364493.
authors: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, #52 Fucheng Road, Haidian District, Beijing, 100142,, P. R. China. goodjf@163.com.
authors: Jifang
authors: J
authors: Gong
authors: Zhongshan Hospital, Fudan University, Shanghai, China. liutianshu@188.com.
authors: Tianshu
authors: T
authors: Liu
authors: The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. FQX2243@126.com.
authors: Qingxia
authors: Q
authors: Fan
authors: General Hospital of the Chinese People's Liberation Army, Beijing, China. Baili0795@yahoo.com.
authors: Li
authors: L
authors: Bai
authors: West China Medical School, West China Hospital, Sichuan University, Chengdu, Sichuan, China. bifeng@medmail.com.cn.
authors: Feng
authors: F
authors: Bi
authors: Cancer Center of People's Liberation Army, 81 Hospital of People's Liberation Army, Nanjing, China. qinsk@csco.org.cn.
authors: Shukui
authors: S
authors: Qin
authors: Cancer Hospital/Institute, Chinese Academy of Medical Sciences, Beijing, China. jwwang@csco.org.cn.
authors: Jinwan
authors: J
authors: Wang
authors: The First Affiliated Hospital of Medical School of Zhejiang University, Hangzhou, Zhejiang, China. xunong@medmail.com.cn.
authors: Nong
authors: N
authors: Xu
authors: Jilin Provincial Cancer Hospital, Changchun, China. Jl.cheng@163.com.
authors: Ying
authors: Y
authors: Cheng
authors: Cancer Hospital, Harbin Medical University, Harbin, China. baiyuxian@126.com.
authors: Yuxian
authors: Y
authors: Bai
authors: Hebei Medical University Fourth Hospital, Hebei Provincial Tumor Hospital, Shijiazhuang, Hebei, China. newhebeiliuwei@163.com.
authors: Wei
authors: W
authors: Liu
authors: Shanghai First People's Hospital, Shanghai, China. yzwlw@yahoo.com.
authors: Liwei
authors: L
authors: Wang
authors: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, #52 Fucheng Road, Haidian District, Beijing, 100142,, P. R. China. lin100@medmail.com.cn.
authors: Lin
authors: L
authors: Shen
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D000069287:Capecitabine / Q000008:administration & dosage*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage*; D000077150:Oxaliplatin; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000068878:Trastuzumab / Q000008:administration & dosage*
chemical_list: D000069287:Capecitabine; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human