[Trastuzumab combined with chemotherapy in patients with HER2-positive chemo-refractory advanced gastric or gastro-esophageal junction adenocarcinoma].
OBJECTIVE
To evaluate the efficacy and safety of trastuzumab combined with chemotherapy in the treatment for HER-2-positive chemo-refractory advanced gastric or gastro-esophageal junction adenocarcinoma.


METHODS
Twenty consecutive cases of chemo-refractory advanced gastric or gastro-esophageal junction adenocarcinoma treated in Peking University Cancer Hospital between 2009 June and 2013 August were included in this study. The patients with adenocarcinoma were previously confirmed and were eligible if their tumor showed overexpression of HER-2+++ by immunohistochemistry or HER-2 gene amplification-positive by FISH, and if they failed to at least one previous chemotherapy. Response and toxicities were evaluated with RECIST 1.0 and CTC AE 3.0 criteria.


RESULTS
The twenty patients received trastuzumab plus second- or later-line chemotherapy, consisting of nine platinum with fluoropyrimidines, five paclitaxel with fluoropyrimidines, three fluoropyrimidines monotherapy, two irinotecan monotherapy, and one docetaxel monotherapy. In these 20 cases, 3 PR (15.0%) and 10 SD (50.0%) were achieved, with a disease control rate of 65.0%. The median PFS was 6.1 months (95%CI 3.0-9.2) and median OS was 11.1 months (95%CI 8.4-13.7). The median cycle number of Trastuzumab administration was 6.5. The patients treated with Trastuzumab ≥ 6 times had a median OS of 13.8 months, significantly longer than that of 9.5 months in the patients treated <6 times (P < 0.001). The patients treated with Trastuzumab ≥ 6 times had a median PFS of 7.8 months, significantly longer than that of 3.7 months in patients treated <6 times (P = 0.029). Among the 20 cases, loss of appetite (13 cases of grade 1-2), neutropenia (12 cases of grade 1-2 and 3 cases of grade 3-4) and fatigue (9 cases of grade 1-2 and 3 cases of grade 3-4) were the most frequent adverse events. No cardiac events including asymptomatic decreases in LVEF ≥ 10% and no treatment-related death were recorded.


CONCLUSIONS
Combination of trastuzumab with chemotherapy is effective and safe in patients with HER2-positive advanced chemo-refractory gastric or gastro-esophageal junction adenocarninoma. However, prospective studies are warranted to further confirm its efficacy and safety.
Key laboratory of Carcinogenesis and Translational Research (Ministry of Education) , Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
Xiaotian
X
Zhang
Key laboratory of Carcinogenesis and Translational Research (Ministry of Education) , Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
Yuanhang
Y
Wu
Key laboratory of Carcinogenesis and Translational Research (Ministry of Education) , Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
Jifang
J
Gong
Key laboratory of Carcinogenesis and Translational Research (Ministry of Education) , Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
Zhihao
Z
Lu
Key laboratory of Carcinogenesis and Translational Research (Ministry of Education) , Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
Jun
J
Zhou
Key laboratory of Carcinogenesis and Translational Research (Ministry of Education) , Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
Xicheng
X
Wang
Key laboratory of Carcinogenesis and Translational Research (Ministry of Education) , Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
Ming
M
Lu
Key laboratory of Carcinogenesis and Translational Research (Ministry of Education) , Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
Jian
J
Li
Key laboratory of Carcinogenesis and Translational Research (Ministry of Education) , Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
Yanshuo
Y
Cao
Key laboratory of Carcinogenesis and Translational Research (Ministry of Education) , Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
Yan
Y
Li
Key laboratory of Carcinogenesis and Translational Research (Ministry of Education) , Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
Jie
J
Li
Key laboratory of Carcinogenesis and Translational Research (Ministry of Education) , Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China. Email: lin100@medmail.com.cn.
Lin
L
Shen
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary / Q000601:surgery; D000328:Adult; D000368:Aged; D000855:Anorexia / Q000139:chemically induced; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D018450:Disease Progression; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D004943:Esophagogastric Junction; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000077146:Irinotecan; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D012074:Remission Induction; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary / Q000601:surgery; D015996:Survival Rate; D000068878:Trastuzumab
D061067:Antibodies, Monoclonal, Humanized; D002166:Camptothecin; D002945:Cisplatin; D000077146:Irinotecan; D017239:Paclitaxel; D011743:Pyrimidines; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C029269:5-fluoropyrimidine