Researchers have conducted a multicenter phase II clinical trial to assess marimastat, an oral matrix metalloproteinase inhibitor, in patients with advanced pancreatic cancer.
Pancreatic cancer has a poor response to conventional chemotherapy and radiotherapy.
Inhibition of matrix metalloproteinase activity involved in tumor invasion and metastases is a novel biological approach for cancer treatment.
A total of 113 patients received marimastat for 28 days at 100 mg b.d. (n = 9), 25 mg o.d. (n = 90) or 10 mg b.d. (n = 14).
Patients with a response to treatment could continue marimastat beyond 28 days.
Of the 113 patients, 90 (80%) completed the 28-day study and 83 (73%) continued treatment.
The principal side-effect was arthralgia in 14 (12%) patients at 28 days, and 33 (29%) patients over the whole study.
| Arthralgia was reported in 29% of patients taking marimastat.
| British Journal of Cancer |
The team found that there were 31 patients (27%) who required dose modification.
Of 76 patients with evaluable CA19-9 levels, 23 (30%) showed no increase or fall in CA19-9.
Of 83 patients with radiologically assessable disease, 41 (49%) had stable disease.
The median survival was found to be 245 days for those with a stable or falling CA19-9 level, and 128 days in those with rising CA19-9.
The overall survival was 3.8 months - 5.9 months for stage II, 4.7 months for stage III, and 3 months for stage IV disease.
The researchers found that, of 90 patients, 46 (51%) had stabilization or reduction in pain, mobility, and analgesia scores.
Author J. D. Evans concluded on behalf of the group, "Further development and clinical evaluation of matrix metalloproteinase inhibitors for the treatment of pancreatic cancer is warranted."