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A phase II trial of marimastat in advanced pancreatic cancer
J D Evans1, A Stark, C D Johnson
1Department of Surgery, Queen Elizabeth Hospital, Birmingham, UK.
Abstract:
Pancreatic cancer has a poor response to conventional chemotherapy and radiotherapy. Inhibition of matrix metalloproteinase activity involved in tumour invasion and metastases is a novel biological approach for cancer treatment. This multicentre phase II clinical trial assessed marimastat, an oral matrix metalloproteinase inhibitor, in patients with advanced pancreatic cancer. 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 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. 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 245 days for those with a stable or falling CA19-9 level 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. Of 90 patients, 46 (51%) had stabilization or reduction in pain, mobility and analgesia scores. Further development and clinical evaluation of matrix metalloproteinase inhibitors for the treatment of pancreatic cancer is warranted.
Insights
Marimastat, a matrix metalloproteinase inhibitor, showed potential in treating advanced pancreatic cancer by stabilizing disease and improving survival. Further clinical evaluation is warranted for this novel cancer treatment approach.
Area of Science:
- Oncology
- Pharmacology
Background:
- Pancreatic cancer exhibits poor response to conventional therapies.
- Matrix metalloproteinase (MMP) inhibition presents a novel strategy targeting tumor invasion and metastasis.
Purpose of the Study:
- To assess the efficacy and safety of marimastat, an oral MMP inhibitor, in patients with advanced pancreatic cancer.
Main Methods:
- A multicenter phase II clinical trial involving 113 patients with advanced pancreatic cancer.
- Patients received varying doses of marimastat (100 mg b.d., 25 mg o.d., or 10 mg b.d.) for 28 days, with options for extended treatment.
- Evaluations included tumor markers (CA19-9), radiological assessment, survival, and pain/mobility scores.
Main Results:
- 80% of patients completed the 28-day study, and 73% continued treatment.
- The primary side effect was arthralgia (29%). Dose modifications were required in 27% of patients.
- Disease stabilization was observed in 49% of patients radiologically, and 30% showed stable or falling CA19-9 levels.
- Median survival was 245 days for patients with stable/falling CA19-9 versus 128 days for those with rising levels.
- Pain and mobility scores improved in 51% of patients.
Conclusions:
- Marimastat demonstrated potential in stabilizing advanced pancreatic cancer and improving patient outcomes, including survival and symptom management.
- The matrix metalloproteinase inhibitor marimastat warrants further clinical development for pancreatic cancer treatment.
- Matrix metalloproteinase inhibitors represent a promising therapeutic avenue for pancreatic cancer, addressing limitations of conventional treatments.