Marimastat as First-Line Therapy for Patients With Unresectable Pancreatic Cancer: A Randomized Trial

• Published in: Journal of clinical oncology Vol. 19; no. 15; pp. 3447 - 3455
• Main Authors: BRAMHALL, S. R, ROSEMURGY, A, BROWN, P. D, BOWRY, C, BUCKELS, J. A. C
• Format: Journal Article
• Language: English
• Published: Baltimore, MD American Society of Clinical Oncology 01.08.2001; Lippincott Williams & Wilkins
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - mortality; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic - adverse effects; Antimetabolites, Antineoplastic - therapeutic use; Antineoplastic agents; Biological and medical sciences; Chemotherapy; Deoxycytidine - adverse effects; Deoxycytidine - analogs & derivatives; Deoxycytidine - therapeutic use; Disease-Free Survival; Dose-Response Relationship, Drug; Enzyme Inhibitors - adverse effects; Enzyme Inhibitors - therapeutic use; Female; Humans; Hydroxamic Acids - adverse effects; Hydroxamic Acids - therapeutic use; Male; Medical sciences; Middle Aged; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - mortality; Pharmacology. Drug treatments; Survival Rate; Adenocarcinoma; Antineoplastic agent; Human; Prognosis; First line; Enzyme; Enzyme inhibitor; Metalloendopeptidases; Malignant tumor; Peptidases; Chemotherapy; Randomization; Treatment; Marimastat; Unresectable; Digestive diseases; Hydrolases; Clinical trial; Pancreas; Pancreatic disease
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2001.19.15.3447

The prognosis for unresectable pancreatic cancer remains dismal (1-year survival rate, < 10%; 5-year survival rate, < 5%). Recent advances in conventional chemotherapy and novel molecular treatment strategies warrant investigation. This, the largest randomized study in pancreatic cancer performed to date, compares marimastat, the first of a new class of agents, with gemcitabine. Four hundred fourteen patients with unresectable pancreatic cancer were randomized to receive marimastat 5, 10, or 25 mg bid or gemcitabine 1,000 mg/m2. The primary end point was survival. Progression-free survival, patient benefit, and safety were also assessed. There was no significant difference in survival between 5, 10, or 25 mg of marimastat and gemcitabine (P =.19). Median survival times were 111, 105, 125, and 167 days, respectively, and 1-year survival rates were 14%, 14%, 20%, and 19%, respectively. There was a significant difference in survival rates between patients treated with gemcitabine and marimastat 5 and 10 mg (P <.003). Both agents were well tolerated, although grade 3 or 4 toxicities were reported in 22% and 12% of the gemcitabine- and marimastat-treated patients, respectively. The major toxicity of marimastat was musculoskeletal (44% of marimastat patients, compared with 12% of gemcitabine patients; musculoskeletal toxicity was severe in only 8% of marimastat patients). The results of this study provide evidence of a dose response for marimastat in patients with advanced pancreatic cancer. The 1-year survival rate for patients receiving marimastat 25 mg was similar to that of patients receiving gemcitabine. In view of the manageable tolerability of marimastat and its ease of administration, further studies are warranted.