Targeted HER2 treatment in advanced gastric cancer.
Amplification of the HER2 gene and over-expression of the HER2 protein in gastric cancer have been shown in a large number of studies. HER2 positivity can be detected in approximately 20% of patients, which is a characteristic associated with poor prognosis. Preclinical in vitro and in vivo studies have demonstrated that both trastuzumab and lapatinib are effective in different gastric cancer models and have thus lead to the initiation of clinical studies. In the first phase III study, the ToGA trial, HER2-positive patients with advanced gastroesophageal and gastric adenocarcinoma were randomized to receive 5-fluorouracil/capecitabine and cisplatin either alone or in combination with trastuzumab. A statically significant gain in overall survival was seen in the patients who received the combined treatment of trastuzumab and chemotherapy. It is expected that the encouraging results from the ToGA trial will have an immediate impact on the management of patients and that routine HER2 testing of patients with advanced gastric cancer will be initiated within a relatively short period of time.
Jørgensen
Jan Trøst
JT
Dx-Rx Institute, Baunevaenget 76, DK-3480 Fredensborg, Denmark. jan.trost@dx-rx.dk
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069287:Capecitabine; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D005784:Gene Amplification; D018734:Genes, erbB-2 / Q000235:genetics*; D006801:Humans; D000077341:Lapatinib; D011799:Quinazolines / Q000008:administration & dosage; D016032:Randomized Controlled Trials as Topic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D016019:Survival Analysis; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000069287:Capecitabine; D002945:Cisplatin; D003841:Deoxycytidine; D005472:Fluorouracil; D000077341:Lapatinib; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human