9618
document
Marimastat as maintenance therapy for patients with advanced gastric cancer : a randomised trial . This randomised , double-blind , placebo-controlled study was designed to evaluate the ability of the orally administered matrix metalloproteinase inhibitor , marimastat , to prolong survival in patients with non-resectable gastric and gastro-oesophageal adenocarcinoma . Three hundred and sixty-nine patients with histological proof of adenocarcinoma , who had received no more than a single regimen of 5-fluorouracil-based chemotherapy , were randomised to receive either marimastat ( 10 mg b.d . ) or placebo . Patients were treated for as long as was tolerable . The primary endpoint was overall survival with secondary endpoints of time to disease progression and quality of life . At the point of protocol-defined study completion ( 85 % mortality in the placebo arm ) there was a modest difference in survival in the intention-to-treat population in favour of marimastat ( P=0.07 log-rank test , hazard ratio=1.23 ( 95 % confidence interval 0.98-1.55 ) ) . This survival benefit was maintained over a further 2 years of follow-up ( P=0.024 , hazard ratio=1.27 ( 1.03-1.57 ) ) . The median survival was 138 days for placebo and 160 days for marimastat , with 2-year survival of 3 % and 9 % respectively . A significant survival benefit was identified at study completion in the pre-defined sub-group of 123 patients who had received prior chemotherapy ( P=0.045 , hazard ratio=1.53 ( 1.00-2.34 ) ) . This benefit increased with 2 years additional follow-up ( P=0.006 , hazard ratio=1.68 ( 1.16-2.44 ) ) , with 2-year survival of 5 % and 18 % respectively . Progression-free survival was also significantly longer for patients receiving marimastat compared to placebo ( P=0.009 , hazard ratio=1.32 ( 1.07-1.63 ) ) . Marimastat treatment was associated with the development of musculoskeletal pain and inflammation . Events of anaemia , abdominal pain , jaundice and weight loss were more common in the placebo arm . This is one of the first demonstrations of a therapeutic benefit for a matrix metalloproteinase inhibitor in cancer patients . The greatest benefit was observed in patients who had previously received chemotherapy . A further randomised study of marimastat in these patients is warranted .
9619
Intervention_Pharmacological
Marimastat
9620
Intervention_Pharmacological
marimastat
9621
Intervention_Pharmacological
marimastat
9622
Intervention_Control
placebo
9623
Intervention_Pharmacological
marimastat
9624
Intervention_Control
placebo
9625
Intervention_Pharmacological
marimastat
9626
Intervention_Pharmacological
marimastat
9627
Intervention_Pharmacological
Marimastat
9628
Intervention_Pharmacological
marimastat
9629
Outcome_Mortality
survival
9630
Outcome_Mortality
overall survival
9631
Outcome_Physical
disease progression
9632
Outcome_Mental
quality of life
9633
Outcome_Mortality
survival benefit
9634
Outcome_Mortality
median survival
9635
Outcome_Mortality
significant survival benefit
9636
Outcome_Mortality
2-year survival
9637
Outcome_Mortality
Progression-free survival
9638
Outcome_Pain
musculoskeletal pain and inflammation
9639
Outcome_Physical
Events of anaemia , abdominal pain , jaundice and weight loss
9640
Participant_Condition
advanced gastric cancer
9641
Participant_Condition
non-resectable gastric and gastro-oesophageal adenocarcinoma
9642
Participant_Sample-size
Three hundred and sixty-nine
9643
Participant_Condition
histological proof of adenocarcinoma
9644
Participant_Sample-size
123