The efficacy and distribution of suramin in the treatment of the 9L gliosarcoma.
Suramin inhibits the stimulation of brain tumor deoxyribonucleic acid synthesis in vitro at concentrations of 200 to 400 mg/ml. This report evaluates suramin in the rodent 9L tumor model. Survival was analyzed by treating 10 tumor-bearing animals with suramin (7 mg/kg/d intraperitoneally) for 7 days, beginning 1 week after implantation, and compared with 20 untreated animals. Tissue distribution was analyzed with reverse-phase high-pressure liquid chromatography in homogenized organs of normal animals. Tumor concentration was measured over time in animals treated with a range of suramin doses, beginning 2 weeks after implantation. Suramin imparted no benefit as tumor-bearing control animals and treated animals survived 24.7 +/- 3.4 days and 24.5 +/- 1.5 days, respectively. In the animals receiving 7 mg/kg/d, renal concentrations of suramin were highest--339.8 +/- 30.9 mg/g as late as 25 days after treatment. Concentration in the brain peaked at only 3.3 +/- 1.3 mg/g after 10 days. Concentration in the tumor peaked at 74.4 +/- 16.5 mg/g the day of the last injection, significantly less than estimated by in vitro studies of efficacy. After injections of 35 mg/kg/d, tumor levels reached 230.9 +/- 139.2 mg/g with no evidence of inhibition of tumor progression. The response to a 7 mg/kg direct brain inoculation of suramin was assessed and compared with saline as a control. Animals treated with suramin died after 1 to 3 hours. Intracerebral hematoma volume at the injection site was 13.9 +/- 10.7 mm3 and 1.9 +/- 3.32 mm3 in the suramin-treated and control animals, respectively (P = 0.02), confirming the reported anticoagulant activity of suramin. Suramin is without efficacy in the 9L model because of poor systemic delivery. Alternative direct inoculation results in lethal local hemorrhage. Further consideration is necessary before the broad clinical application of this drug.
Olson
J J
JJ
Department of Neurosurgery, Emory University School of Medicine, Atlanta, Georgia.
Polk
D M
DM
Reisner
A
A
D000818:Animals; D001932:Brain Neoplasms / Q000473:pathology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D018316:Gliosarcoma / Q000473:pathology*; D008297:Male; D009368:Neoplasm Transplantation; D051381:Rats; D011916:Rats, Inbred F344; D013498:Suramin / Q000493:pharmacokinetics / Q000494:pharmacology*; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000473:pathology; D014410:Tumor Stem Cell Assay
D013498:Suramin