Marimastat (BB-2516) is the first
matrix metalloproteinase inhibitor to have entered clinical trials in the field of oncology. It has excellent bioavailability and has completed phase I and II trials. Phase I studies involved healthy volunteers who received short courses of
marimastat; these were well tolerated. Symptoms experienced by many patients with various
malignancies included severe joint and
muscle pain which were debilitating in >60% of patients at doses >50 mg bid. These symptoms were reversible on discontinuation of the
drug, and their incidence has been decreased by using
marimastat 10 mg bid, the dose used in current studies. Phase II studies involved the use of serum
tumor markers as surrogate indicators of antitumor activity. Six studies in colorectal, ovarian, and
prostate cancer have been completed and pooled analysis has demonstrated a dose-dependent
biological effect (as defined by the authors); 58% of patients respond at doses >50 mg bid. Effects on
tumor markers were associated with increased survival. Small phase II studies have suggested potential activity in pancreatic and
gastric cancer and have demonstrated the safety of combining cytotoxic chemotherapeutic agents with
marimastat. Ongoing phase III studies are investigating the effects of
marimastat in addition to
chemotherapy in the treatment of
small cell lung cancer and pancreatic and gastric
carcinoma.