A prospective study of suramin-induced peripheral neuropathy.
Suramin is an investigational drug that has shown therapeutic activity in hormone-refractory metastatic prostate cancer in Phase I/II trials. Dose-limiting neurotoxicity remains the most serious complication of suramin treatment. We performed a prospective study to define the incidence, severity, characteristics, and dose relationships of suramin-induced peripheral neuropathy. Twenty-two patients who received suramin in a Phase-I trial underwent baseline and serial follow-up neurological evaluations consisting of history, examination, nerve conduction studies and quantitative sensory testing (QST). Suramin was administered intravenously in escalating dosages by using a 5-day schedule (repeated monthly), with the dose, determined by a population pharmacokinetic model, to accomplish 30-min post-infusion concentrations of 300 micrograms ml-1 (cohort I), 350 micrograms m-1 (cohort II) and 400 micrograms ml-1 (cohort III). Twelve patients developed a mild, axonal, length-dependent, sensory-motor poly-neuropathy. Three other patients developed a subacutely progressive, functionally disabling, demyelinating neuropathy; sural nerve biopsy in two patients showed lymphocytic inflammation. These three patients improved after drug discontinuation and plasmapheresis. Although there was no apparent correlation between the cumulative dose and the severity of the neuropathy, no patient from cohort I, but 88% of patients from cohorts II and III, developed neuropathy. We conclude that when suramin is used at peak concentrations of > or = 350 micrograms ml-1 its administration is associated with two patterns of neuropathy, a distal axonal neuropathy and an inflammatory demyelinating neuropathy that is partially reversible. Neurological monitoring for development of neuropathy will improve the safety of suramin use in future clinical studies.
Chaudhry
V
V
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Eisenberger
M A
MA
Sinibaldi
V J
VJ
Sheikh
K
K
Griffin
J W
JW
Cornblath
D R
DR
D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001369:Axons / Q000473:pathology; D002986:Clinical Trials as Topic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009431:Neural Conduction; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000473:pathology; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000188:drug therapy; D013498:Suramin / Q000009:adverse effects*
D000970:Antineoplastic Agents; D013498:Suramin