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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS029769-02
Application #
3416657
Study Section
Experimental Therapeutics Subcommittee 1 (ET)
Project Start
1992-04-01
Project End
1995-03-31
Budget Start
1993-04-01
Budget End
1994-03-31
Support Year
2
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
City
Rochester
State
MN
Country
United States
Zip Code
55905
Windebank, A J (1999) Chemotherapeutic neuropathy. Curr Opin Neurol 12:565-71
Gill, J S; Schenone, A E; Podratz, J L et al. (1998) Autocrine regulation of neurite outgrowth from PC12 cells by nerve growth factor. Brain Res Mol Brain Res 57:123-31
Schenone, A; Gill, J S; Zacharias, D A et al. (1996) Expression of high- and low-affinity neurotrophin receptors on human transformed B lymphocytes. J Neuroimmunol 64:141-9
Sun, X; Windebank, A J (1996) Calcium in suramin-induced rat sensory neuron toxicity in vitro. Brain Res 742:149-56
Gill, J S; Connolly, D C; McManus, M J et al. (1996) Suramin induces phosphorylation of the high-affinity nerve growth factor receptor in PC12 cells and dorsal root ganglion neurons. J Neurochem 66:963-72
Gill, J S; Hobday, K L; Windebank, A J (1995) Mechanism of suramin toxicity in stable myelinating dorsal root ganglion cultures. Exp Neurol 133:113-24
Russell, J W; Windebank, A J; Podratz, J L (1994) Role of nerve growth factor in suramin neurotoxicity studied in vitro. Ann Neurol 36:221-8