Combined analysis of studies of the effects of the matrix metalloproteinase inhibitor marimastat on serum tumor markers in advanced cancer: selection of a biologically active and tolerable dose for longer-term studies.
This combined analysis investigated the effect of marimastat, a specific inhibitor of matrix metalloproteinases, on markers of tumor progression measured in patients with advanced cancer. By defining the tolerability and biological activity of the drug, it aimed to establish an appropriate dose range for use in Phase III trials. Patients with advanced, serologically progressive ovarian, prostatic, pancreatic, and colorectal cancer were recruited into six nonrandomized, dose ranging, multicenter clinical trials in North America and Europe. The biological activity of marimastat was assessed by serial measurements of the serum tumor markers carcinoembryonic antigen, CA125, CA19-9, and prostate-specific antigen. Patients were recruited with tumor markers rising by more than 25% averaged over a 4-week screening period. A biological effect was defined as a level of tumor marker at the end of treatment no greater than at study entry; a partial biological effect was defined as a rise in the level of tumor marker over the treatment period of 0-25% per 4 weeks. Pharmacokinetic and safety data were collected and assessed as the studies progressed. All patients were followed up for survival.
Nemunaitis
J
J
Texas Oncology Center, Dallas 75246, USA.
Poole
C
C
Primrose
J
J
Rosemurgy
A
A
Malfetano
J
J
Brown
P
P
Berrington
A
A
Cornish
A
A
Lynch
K
K
Rasmussen
H
H
Kerr
D
D
Cox
D
D
Millar
A
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D014408:Biomarkers, Tumor / Q000097:blood*; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006877:Hydroxamic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D008875:Middle Aged; D009367:Neoplasm Staging; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate
D014408:Biomarkers, Tumor; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; C100342:marimastat; D008666:Metalloendopeptidases