A phase II trial of marimastat in advanced pancreatic cancer.

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.

• Authors: J D Evans, A Stark, C D Johnson, F Daniel, J Carmichael, J Buckels, C W Imrie, P Brown, J P Neoptolemos
• Journal: British journal of cancer (Br J Cancer) Vol. 85 Issue 12 Pg. 1865-70 (Dec 14 2001) ISSN: 0007-0920 [Print] England
• PMID: 11747327 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Multicenter Study)

Chemical References

• Biomarkers, Tumor
• CA-19-9 Antigen
• Hydroxamic Acids
• Neoplasm Proteins
• Protease Inhibitors
• marimastat
• Metalloendopeptidases

Topics

• Adenocarcinoma (drug therapy, enzymology, mortality)
• Administration, Oral
• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor (blood)
• CA-19-9 Antigen (blood)
• Female
• Gastrointestinal Diseases (chemically induced)
• Humans
• Hydroxamic Acids (administration & dosage, adverse effects, therapeutic use)
• Life Tables
• Male
• Metalloendopeptidases (antagonists & inhibitors)
• Middle Aged
• Musculoskeletal Diseases (chemically induced)
• Neoplasm Proteins (antagonists & inhibitors)
• Neoplasm Staging
• Pain (etiology)
• Palliative Care
• Pancreatic Neoplasms (drug therapy, enzymology, mortality)
• Pilot Projects
• Protease Inhibitors (administration & dosage, adverse effects, therapeutic use)
• Quality of Life
• Survival Analysis
• Treatment Outcome