Within a combination chemotherapy regimen , oral capecitabine is preferred over intravenous 5-fluorouracil (5fu)-that is , epirubicin-cisplatin-capecitabine is preferred over the prior st and ard regimen , epirubicin-cisplatin-5fu (ecf).Epirubicin-oxaliplatin-capecitabine ( eox ) is a reasonable alternative to ecf .
QUESTION What is the optimal chemotherapy regimen in advanced gastric cancer ?
PERSPECTIVES Gastric cancer is the second leading cause of cancer mortality worldwide .
Despite low incidence rates for gastric cancer in Ontario , the overall prognosis is bleak , with 5-year survival rates of approximately 23 % in Canada .
Even with the considerable body of research available on chemotherapy for advanced gastric cancer , uncertainty remains .
There is no recognized st and ard treatment , and there appears to be geographic variation in practice .
Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial
BACKGROUND Trastuzumab , a monoclonal antibody against human epidermal growth factor receptor 2 ( HER2 ; also known as ERBB2 ) , was investigated in combination with chemotherapy for first-line treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer . METHODS ToGA ( Trastuzumab for Gastric Cancer ) was an open-label , international , phase 3 , r and omised controlled trial undertaken in 122 centres in 24 countries . Patients with gastric or gastro-oesophageal junction cancer were eligible for inclusion if their tumours showed overexpression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in-situ hybridisation . Participants were r and omly assigned in a 1:1 ratio to receive a chemotherapy regimen consisting of capecitabine plus cisplatin or fluorouracil plus cisplatin given every 3 weeks for six cycles or chemotherapy in combination with intravenous trastuzumab . Allocation was by block r and omisation stratified by Eastern Cooperative Oncology Group performance status , chemotherapy regimen , extent of disease , primary cancer site , and measurability of disease , implemented with a central interactive voice recognition system . The primary endpoint was overall survival in all r and omised patients who received study medication at least once . This trial is registered with Clinical Trials.gov , number NCT01041404 . FINDINGS 594 patients were r and omly assigned to study treatment ( trastuzumab plus chemotherapy , n=298 ; chemotherapy alone , n=296 ) , of whom 584 were included in the primary analysis ( n=294 ; n=290 ) . Median follow-up was 18.6 months ( IQR 11 - 25 ) in the trastuzumab plus chemotherapy group and 17.1 months ( 9 - 25 ) in the chemotherapy alone group . Median overall survival was 13.8 months ( 95 % CI 12 - 16 ) in those assigned to trastuzumab plus chemotherapy compared with 11.1 months ( 10 - 13 ) in those assigned to chemotherapy alone ( hazard ratio 0.74 ; 95 % CI 0.60 - 0.91 ; p=0.0046 ) . The most common adverse events in both groups were nausea  ( trastuzumab plus chemotherapy , 197 [ 67 % ] vs chemotherapy alone , 184 [ 63 % ] ) , vomiting ( 147 [ 50 % ] vs 134 [ 46 % ] ) , and neutropenia ( 157 [ 53 % ] vs 165 [ 57 % ] ) . Rates of overall grade 3 or 4 adverse events ( 201 [ 68 % ] vs 198 [ 68 % ] ) and cardiac adverse events ( 17 [ 6 % ] vs 18 [ 6 % ] ) did not differ between groups . INTERPRETATION Trastuzumab in combination with chemotherapy can be considered as a new st and ard option for patients with HER2-positive advanced gastric or gastro-oesophageal junction cancer . FUNDING F Hoffmann-La Roche
Within a combination chemotherapy regimen , oral capecitabine is preferred over intravenous 5-fluorouracil (5fu)-that is , epirubicin-cisplatin-capecitabine is preferred over the prior st and ard regimen , epirubicin-cisplatin-5fu (ecf).Epirubicin-oxaliplatin-capecitabine ( eox ) is a reasonable alternative to ecf .
QUESTION What is the optimal chemotherapy regimen in advanced gastric cancer ?
PERSPECTIVES Gastric cancer is the second leading cause of cancer mortality worldwide .
Despite low incidence rates for gastric cancer in Ontario , the overall prognosis is bleak , with 5-year survival rates of approximately 23 % in Canada .
Even with the considerable body of research available on chemotherapy for advanced gastric cancer , uncertainty remains .
There is no recognized st and ard treatment , and there appears to be geographic variation in practice .