Phase I study of intraperitoneal metalloproteinase inhibitor BB94 in patients with malignant ascites.
This was an open Phase I study of i.p. matrix metalloproteinase inhibitor BB94 in patients with malignant ascites. The objective of the study was to determine the effect of increasing i.p. doses of BB94 with reference to the tolerance, safety, and pharmacokinetics of the compound. Twenty-three patients with malignant ascites had BB94 instilled into the peritoneal cavity after paracentesis. The compound was well tolerated; no serious adverse events were seen, and no specific toxicities were observed. High plasma concentrations were seen an hour after dosing, and BB94 was still present in the plasma at day 28 after treatment at levels in excess of the IC50 identified in preclinical studies. Five of the 23 patients neither reaccumulated ascites nor died up to 112 days after dosing. Seven patients died without reaccumulating ascites. Although the study was not designed to demonstrate clinical efficacy, the results were encouraging and support the further therapeutic evaluation of matrix metalloproteinase inhibitors in the management of malignant ascites.
Beattie
G J
GJ
Department of Obstetrics and Gynaecology, St John's Hospital at Howden, West Lothian, United Kingdom.
Smyth
J F
JF
D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001201:Ascites / Q000188:drug therapy / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors; D008875:Middle Aged; D009369:Neoplasms / Q000378:metabolism*; D010649:Phenylalanine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013876:Thiophenes / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D011480:Protease Inhibitors; D013876:Thiophenes; D010649:Phenylalanine; C080985:batimastat; D008666:Metalloendopeptidases