A prospective study of suramin-induced peripheral neuropathy

Research output: Contribution to journalArticle

Abstract

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 ug ml-1 (cohort I), 350 ug m-1 (cohort II) and 400 ug ml-1 (cohort III). Twelve patients developed a mild, axonal, length-dependant, 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 ug 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.

Original languageEnglish (US)
Pages (from-to)2039-2052
Number of pages14
JournalBrain
Volume119
Issue number6
DOIs
StatePublished - Jan 1 1996

    Fingerprint

Keywords

  • Guillain-Barre syndrome
  • Prostate cancer
  • Suramin
  • Total neuropathy score
  • Toxic neuropathy

ASJC Scopus subject areas

  • Clinical Neurology

Cite this