The randomized clinical trial compared the effects of three different doses of marimastat with the chemotherapy drug gemcitabine in 414 patients with advanced pancreatic cancer. During this clinical trial, gemcitabine was approved for use in pancreatic cancer, and is now considered the standard of care.
According to the study, the one-year survival rate for patients with localized cancer was 20 percent for patients given the highest dose of marimastat and 19 percent for patients treated with gemcitabine. Although patients taking gemcitabine reported greater improvements in pain and mood, fewer toxic side effects (e.g., pulmonary complications and nausea) were reported in patients taking marimastat versus gemcitabine (12 percent versus 22 percent, respectively).
Marimastat did not show benefit in lower doses or in patients with metastatic pancreatic cancer. The one-year survival rate for patients taking lower doses of marimastat was 14 percent.
Researchers say marimastat appears to benefit some non-metastatic patients and suggest the agent be tested in those patients in combination with gemcitabine. "Five years ago, patients with advanced pancreatic cancer did not have any good treatment options, but gemcitabine and newly engineered drugs like marimastat are giving us hope," says the study leader Simon Bramhall, from the Queen Elizabeth Hospital, Birmingham, England. "These clinical trial results are encouraging and suggest that targeted molecular therapy may benefit some patients."
Matrix metalloproteinase inhibitors restrict the growth and spread of solid tumors by blocking blood vessel growth to the site of tumors. Marimastat is also being tested in ovarian and gastric cancers.
"Marimastat as First-Line Therapy for Patients With Unresectable Pancreatic Cancer: A Randomized Trial." S.R. Bramhall, et al.; Queen Elizabeth Hospital, Birmingham, United Kingdom, Vol 19, No 15, August 1, 2001, pp: 3447-3455.