Brain, Vol. 119, No. 6, 2039-2052, 1996
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A prospective study of suramin-induced peripheral neuropathy
1Departments of Neurology, Johns Hopkins University School of Medicine Baltimore, Maryland, USA 2Departments of Oncology, Johns Hopkins University School of Medicine Baltimore, Maryland, USA 3Departments of Neuroscience, Johns Hopkins University School of Medicine Baltimore, Maryland, USA
Correspondence to:
Correspondence to: V. Chaudhry. Department of Neurology, Johns Hopkins Hospital. Pathology 509, 600 North Wolfe Street, Baltimore, MD 2128, USA
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 µg ml–1 (cohort I), 350 µg m–1 (cohort II) and 400 µg ml–1 (cohort III). Twelve patients developed a mild, axonal, length-dependent, sensory-motor polyneuropathy. 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 
350 µg 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.
toxic neuropathy; suramin; Guillain-Barré syndrome; prostate cancer; total neuropathy score
Received March 27, 1996. Revised June 13, 1996. Accepted August 2, 1996.
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