A phase II trial of marimastat in advanced pancreatic cancer
Evans, J.D., Stark, A., Johnson, C.D., Daniel, F., Carmichael, J., Buckels, J., Imrie, C.W., Brown, P. and Neoptolemos, J.P. (2001) A phase II trial of marimastat in advanced pancreatic cancer. British Journal of Cancer, 85, (12), 1865-1870.
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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.
|Keywords:||pancreatic cancer, matrix metalloproteinases, marimastat, toxicity|
|Subjects:||R Medicine > RS Pharmacy and materia medica
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
|Divisions:||University Structure - Pre August 2011 > School of Medicine > Cancer Sciences
|Date Deposited:||24 Apr 2006|
|Last Modified:||01 Jun 2011 06:28|
|Contributors:||Evans, J.D. (Author)
Stark, A. (Author)
Johnson, C.D. (Author)
Daniel, F. (Author)
Carmichael, J. (Author)
Buckels, J. (Author)
Imrie, C.W. (Author)
Brown, P. (Author)
Neoptolemos, J.P. (Author)
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