A pilot study of the safety and effects of the matrix metalloproteinase inhibitor marimastat in gastric cancer

The aim of this study was to evaluate the safety and tolerability of 4 week s administration of marimastat, and to seek evidence of biological activity as observed by changes in the endoscopic appearance of the gastric tumours . 35 patients with advanced, inoperable gastric or gastro-oesophageal tumou rs were recruited. The dose of marimastat was reduced from the starting dos e of 50 mg twice daily (6 patients) to 25 mg once daily (29 patients). 31 c ompleted the 28 day study period. Marimastat was generally well tolerated, with the principal treatment-related toxicity being pain and stiffness of t he musculoskeletal system. These symptoms occurred more frequently at the h igher-dose, and increased to involve a total of 13 patients (37%) with long er-term treatment. The events were usually rapidly reversible on drug disco ntinuation. 3 patients receiving prolonged treatment experienced more sever e symptoms, with the development of skin thickening and contractures in the hands. At endoscopy, 10 patients showed an increased fibrotic cover of the tumour, 8 had decreased haemorrhagic appearance, and in at least 2 cases w here comparative tumour histology was assessable, there was evidence of inc reased stromal fibrotic tissue. (C) 1999 Elsevier Science Ltd. All rights r eserved.