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 .
AVAGAST: A randomized, double-blind, placebo-controlled, phase III study of first-line capecitabine and cisplatin plus bevacizumab or placebo in patients with advanced gastric cancer (AGC).
LBA4007 Background : The median survival for patients ( pts ) with AGC in most phase III studies is less than 1 year . The addition of bevacizumab ( bev ) to chemotherapy ( chemo ) is supported by a strong pre clinical rationale and by phase II evaluation . AVAGAST is the first r and omized study to compare the efficacy and safety of bev + chemo vs placebo + chemo . METHODS Pts with inoperable , locally advanced or metastatic stomach/gastroesophageal junction adenocarcinoma with no prior therapy were r and omized 1:1 to capecitabine ( cape , or 5-FU ) + cisplatin ( cis ) and either bev ( 7.5 mg/kg iv ) or placebo q3w . Stratification variables : geographical region , fluoropyrimidine treatment , disease status . Cis was given for 6 cycles ; bev/placebo + cape/5-FU were given until disease progression or unmanageable toxicity . PRIMARY OBJECTIVE compare overall survival ( OS ) ; secondary objectives : compare progression-free survival ( PFS ) , overall response rate ( ORR ) , and safety ( as overseen by an independent DSMB ) . RESULTS From Sep 2007 to Dec 2008 , 774 pts were enrolled . Treatment arms were balanced . Approx 95 % of pts were metastatic . Two-thirds of pts were male , 49 % of pts were from Asia/Pacific , 32 % from Europe and 19 % from the Americas . Median OS was 10.1 months with chemo + placebo and 12.1 months with chemo + bev in the intent-to-treat population ( HR 0.87 ; p=0.1002 ) . Median OS according to geographical region was 6.8 vs. 11.5 months ( HR 0.63 ) in the Americas , 8.6 vs. 11.1 months ( HR 0.85 ) in Europe and 12.1 vs. 13.9 months in Asia-Pacific ( HR 0.97 ) . Secondary endpoints and AEs of special interest for Bev are summarized below ( Table ) . CONCLUSIONS While the primary endpoint was not met ( median OS HR 0.87 ; p=0.1002 ) , there was a significant improvement in PFS and ORR and an acceptable safety profile for bev + chemo in patients with AGC . [ Table : see text ] [ Table : see text ]
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 .