IN VITRO STUDIES OF SURAMIN NEUROTOXICITY

Sodium suramin is a promising chemotherapeutic agent with possible efficacy against prostate and adrenal cancer. It is being used in phase II trials for patients with advanced D2 cancer of the prostate in a multicenter trial. One of the major adverse effects observed in preliminary trials was a severe peripheral neuropathy. In the studies proposed, patients entered into clinical trials of suramin will be studied prospectively to identify the appearance of peripheral nerve injury. Sensitive quantitative techniques (Neuropathy Symptom Score, Neurologic Disability Score, Computer Assisted Sensory Examination, Nerve Conduction Studies, Needle Electromyography, and Quantitative Autonomic Examination) will be used at baseline and at intervals during therapy. The characteristics of the neuropathy in terms of fiber class loss and fiber pathology (axonal degeneration versus demyelination) will be determined by study of nerve biopsy. Weekly estimation of serum suramin will allow correlation of development of neuropathy with duration and level of exposure to the drug. This adverse effect will be compared to tumor regression to determine if a therapeutic window exists. Those patients developing neuropathy will be studied for 12 months following cessation of therapy to determine whether the neuropathy is reversible.