A double-blind placebo-controlled, randomised study comparing gemcitabine and marimastat with gemcitabine and placebo as first line therapy in patients with advanced pancreatic cancer

• Published in: British journal of cancer Vol. 87; no. 2; pp. 161 - 167
• Main Authors: BRAMHALL, S. R, SCHULZ, J, NEMUNAITIS, J, BROWN, P. D, BAILLET, M, BUCKETS, J. A. C
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 15.07.2002
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - mortality; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic - adverse effects; Antimetabolites, Antineoplastic - therapeutic use; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Chemotherapy; Clinical; Deoxycytidine - administration & dosage; Deoxycytidine - adverse effects; Deoxycytidine - analogs & derivatives; Deoxycytidine - therapeutic use; Disease Progression; Disease-Free Survival; Double-Blind Method; Female; Humans; Hydroxamic Acids - administration & dosage; Hydroxamic Acids - adverse effects; Life Tables; Male; Matrix Metalloproteinase Inhibitors; Medical sciences; Middle Aged; Musculoskeletal Diseases - chemically induced; Neoplasm Proteins - antagonists & inhibitors; Pancreatic cancer; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - mortality; Pharmacology. Drug treatments; Protease Inhibitors - administration & dosage; Protease Inhibitors - adverse effects; Quality of Life; Safety; Survival Analysis; British Isles; Adenocarcinoma; Antineoplastic agent; Prognosis; Intravenous administration; Gemcitabine; Toxicity; Metalloendopeptidases; Randomization; Marimastat; Complication; Advanced stage; Pancreas; Pyrimidine nucleoside; Pancreatic disease; Human; Drug combination; Enzyme; Treatment efficiency; Oral administration; Enzyme inhibitor; Malignant tumor; Peptidases; Chemotherapy; Treatment; Antimetabolic; Double blind study; Digestive diseases; Hydrolases; Fluorine Organic compounds; Comparative study
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6600446

Pancreatic cancer is the fifth most common cause of cancer death in the western world and the prognosis for unresectable disease remains poor. Recent advances in conventional chemotherapy and the development of novel 'molecular' treatment strategies with different toxicity profiles warrant investigation as combination treatment strategies. This randomised study in pancreatic cancer compares marimastat (orally administered matrix metalloproteinase inhibitor) in combination with gemcitabine to gemcitabine alone. Two hundred and thirty-nine patients with unresectable pancreatic cancer were randomised to receive gemcitabine (1000 mg m(-2)) in combination with either marimastat or placebo. The primary end-point was survival. Objective tumour response and duration of response, time to treatment failure and disease progression, quality of life and safety were also assessed. There was no significant difference in survival between gemcitabine and marimastat and gemcitabine and placebo (P=0.95 log-rank test). Median survival times were 165.5 and 164 days and 1-year survival was 18% and 17% respectively. There were no significant differences in overall response rates (11 and 16% respectively), progression-free survival (P=0.68 log-rank test) or time to treatment failure (P=0.70 log-rank test) between the treatment arms. The gemcitabine and marimastat combination was well tolerated with only 2.5% of patients withdrawn due to presumed marimastat toxicity. Grade 3 or 4 musculoskeletal toxicities were reported in only 4% of the marimastat treated patients, although 59% of marimastat treated patients reported some musculoskeletal events. The results of this study provide no evidence to support a combination of marimastat with gemcitabine in patients with advanced pancreatic cancer. The combination of marimastat with gemcitabine was well tolerated. Further studies of marimastat as a maintenance treatment following a response or stable disease on gemcitabine may be justified.