A team from the United Kingdom evaluated the ability of orally administered marimastat to prolong survival in patients with non-resectable gastric and gastroesophageal adenocarcinoma.
A total of 369 patients with histological proof of adenocarcinoma, who had received no more than a single regimen of 5-fluorouracil-based chemotherapy, were included in the study.
Each was randomized to receive either marimastat (10 mg twice daily) 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 study completion (85% mortality in the placebo arm), there was a modest difference in survival in the intention-to-treat population in favor of marimastat (hazard ratio = 1.23).
This survival benefit was maintained over a further 2 years of follow-up (hazard ratio = 1.27).
The median survival was 138 days for placebo and 160 days for marimastat, with 2-year survival of 3% and 9%, respectively.
In addition, a significant survival benefit was identified at study completion in a sub-group of 123 patients who had received prior chemotherapy (hazard ratio = 1.53).
|2-year survival rates:|
| British Journal of Cancer |
This benefit increased with 2 years additional follow-up (hazard ratio = 1.68), with 2-year survival of 5% and 18%, respectively.
Progression-free survival was also significantly longer for patients receiving marimastat compared to placebo (hazard ratio = 1.32).
However, marimastat treatment was associated with the development of musculoskeletal pain and inflammation.
Events of anemia, abdominal pain, jaundice, and weight loss were more common in the placebo arm.
Dr S. R. Bramhall, of the Queen Elizabeth Hospital, Birmingham, England, concluded on behalf of fellow authors, "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 randomized study of marimastat in these patients is warranted."