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 weeks 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 tumours were recruited. The dose of marimastat was reduced from the starting dose of 50 mg twice daily (6 patients) to 25 mg once daily (29 patients). 31 completed the 28 day study period. Marimastat was generally well tolerated, with the principal treatment-related toxicity being pain and stiffness of the musculoskeletal system. These symptoms occurred more frequently at the higher-dose, and increased to involve a total of 13 patients (37%) with longer-term treatment. The events were usually rapidly reversible on drug discontinuation. 3 patients receiving prolonged treatment experienced more severe 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 where comparative tumour histology was assessable, there was evidence of increased stromal fibrotic tissue.
Tierney
G M
GM
Department of Surgery, University Hospital, Queen's Medical Centre, Nottingham, U.K.
Griffin
N R
NR
Stuart
R C
RC
Kasem
H
H
Lynch
K P
KP
Lury
J T
JT
Brown
P D
PD
Millar
A W
AW
Steele
R J
RJ
Parsons
S L
SL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D008875:Middle Aged; D010865:Pilot Projects; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016896:Treatment Outcome
D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; C100342:marimastat; D008666:Metalloendopeptidases