Directed intravascular precipitation of bisantrene for pelvic malignant lesions: preclinical studies.
Bisantrene, a clinically active anticancer drug with limited solubility at physiologic pH, was delivered by selective injection into the internal iliac artery of male calves. The percutaneous transfemoral angiographic techniques used in the calves were identical to those used in adult human patients. Directed intravascular precipitation of bisantrene at the maximal tolerable clinical dose for intravenous administration (260 mg/m2) caused severe tissue damage in 5 of 10 animals that received these intra-arterial injections. (One calf in this study group died of unknown causes 10 days after the drug infusion). A reduced intra-arterial dose (50 mg/m2) was used in seven calves, and no local tissue damage was evident on gross or microscopic examination. Nevertheless, resultant concentrations of bisantrene deposited in the ipsilateral bladder wall were 10- to 100-fold those concentrations found after intravenous administration of a dose 5 times higher. These animal toxicology and pharmacology data support initiation of a phase I clinical trial of directed intravascular precipitation of bisantrene in humans. This clinical trial will be developed for patients with advanced refractory cancers of the anatomic true pelvis, such as those originating in the urinary bladder, prostate, rectum, and uterine cervix.
D000792:Angiography; D000818:Animals; D000873:Anthracenes / Q000378:metabolism / Q000627:therapeutic use / Q000633:toxicity; D002417:Cattle; D004353:Drug Evaluation, Preclinical; D006863:Hydrogen-Ion Concentration; D007083:Iliac Artery; D007261:Infusions, Intra-Arterial; D008297:Male; D014018:Tissue Distribution; D001745:Urinary Bladder Diseases / Q000139:chemically induced* / Q000473:pathology; D014565:Urogenital Neoplasms / Q000188:drug therapy
D000873:Anthracenes; C031404:bisantrene