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 intraperi
toneally) for 7 days, beginning 1 week after implantation, and compare
d with 20 untreated animals. Tissue distribution was analyzed with rev
erse-phase high-pressure liquid chromatography in homogenized organs o
f normal animals. Tumor concentration was measured over time in animal
s treated with a range of suramin doses, beginning 2 weeks after impla
ntation. 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 i
n vitro studies of efficacy. After injections of 35 mg/kg/d, tumor lev
els reached 230.9 +/- 139.2 mg/g with no evidence of inhibition of tum
or progression. The response to a 7 mg/kg direct brain inoculation of
suramin was assessed and compared with saline as a control. Animals tr
eated with suramin died after 1 to 3 hours. Intracerebral hematoma vol
ume at the injection site was 13.9 +/- 10.7 mm(3) and 1.9 +/- 3.32 mm(
3) in the suramin-treated and control animals, respectively (P = 0.02)
, confirming the reported anticoagulant activity of suramin. Suramin i
s without efficacy in the 9L model because of poor systemic delivery.
Alternative direct inoculation results in lethal local hemorrhage. Fur
ther consideration is necessary before the broad clinical application
of this drug.