A phase II trial of marimastat in advanced pancreatic cancer.
Pancreatic cancer has a poor response to conventional chemotherapy and radiotherapy. Inhibition of matrix metalloproteinase activity involved in tumour invasion and metastases is a novel biological approach for cancer treatment. This multicentre phase II clinical trial assessed marimastat, an oral matrix metalloproteinase inhibitor, in patients with advanced pancreatic cancer. A total of 113 patients received marimastat for 28 days at 100 mg b.d. (n = 9), 25 mg o.d. (n = 90) or 10 mg b.d. (n = 14). Patients with a response to treatment could continue marimastat beyond 28 days. Of 113 patients, 90 (80%) completed the 28-day study and 83 (73%) continued treatment. The principal side effect was arthralgia in 14 (12%) patients at 28 days and 33 (29%) patients over the whole study. There were 31 patients (27%) who required dose modification. Of 76 patients with evaluable CA19-9 levels, 23 (30%) showed no increase or fall in CA19-9. Of 83 patients with radiologically assessable disease, 41 (49%) had stable disease. The median survival was 245 days for those with a stable or falling CA19-9 level 128 days in those with rising CA19-9. The overall survival was 3.8 months. 5.9 months for stage II, 4.7 months for stage III and 3 months for stage IV disease. Of 90 patients, 46 (51%) had stabilization or reduction in pain, mobility and analgesia scores. Further development and clinical evaluation of matrix metalloproteinase inhibitors for the treatment of pancreatic cancer is warranted.
Evans
J D
JD
Department of Surgery, Queen Elizabeth Hospital, Birmingham, UK.
Stark
A
A
Johnson
C D
CD
Daniel
F
F
Carmichael
J
J
Buckels
J
J
Imrie
C W
CW
Brown
P
P
Neoptolemos
J P
JP
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood; D018395:CA-19-9 Antigen / Q000097:blood; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015993:Life Tables; D008297:Male; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D008875:Middle Aged; D009140:Musculoskeletal Diseases / Q000139:chemically induced; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors*; D009367:Neoplasm Staging; D010146:Pain / Q000209:etiology; D010166:Palliative Care; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality; D010865:Pilot Projects; D011480:Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011788:Quality of Life; D016019:Survival Analysis; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D018395:CA-19-9 Antigen; D006877:Hydroxamic Acids; D009363:Neoplasm Proteins; D011480:Protease Inhibitors; C100342:marimastat; D008666:Metalloendopeptidases