A prospective study of suramin-induced peripheral neuropathy

被引:58
作者
Chaudhry, V
Eisenberger, MA
Sinibaldi, VJ
Sheikh, K
Griffin, JW
Cornblath, DR
机构
[1] JOHNS HOPKINS UNIV, SCH MED, DEPT NEUROL, BALTIMORE, MD 21205 USA
[2] JOHNS HOPKINS UNIV, SCH MED, DEPT ONCOL, BALTIMORE, MD 21205 USA
[3] JOHNS HOPKINS UNIV, SCH MED, DEPT NEUROSCI, BALTIMORE, MD 21205 USA
关键词
toxic neuropathy; suramin; Guillain-Barre syndrome; prostate cancer; total neuropathy score;
D O I
10.1093/brain/119.6.2039
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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 mu g ml(-1) (cohort I), 350 mu g m(-1) (cohort II) and 400 mu g ml(-1) (cohort III). Twelve patients developed a mild, axonal, length-dependent, sensory-motor polyneuropathy. The other three 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 greater than or equal to 350 mu g ml(-1) it 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.
引用
收藏
页码:2039 / 2052
页数:14
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