An electrodiagnostic evaluation of the effect of pre-existing peripheral nervous system disorders in patients treated with the novel proteasome inhibitor bortezomib.
OBJECTIVE
Bortezomib (Velcade), a novel proteasome inhibitor, has shown promise in the treatment of malignancies, including multiple myeloma and non-Hodgkin's lymphoma. Several studies have identified neuropathy as a potentially dose-limiting side effect of treatment with bortezomib. We report the clinical and electrodiagnostic data from four patients who developed signs and symptoms of peripheral neuropathy from treatment with bortezomib.


METHODS
Patients were included if they were enrolled in active phase 2 trials of bortezomib for non-Hodgkin's lymphoma or prostate cancer, developed signs and symptoms of peripheral neuropathy, and were referred for electrodiagnostic evaluation.


RESULTS
Four patients, including two with non-Hodgkin's lymphoma and two with prostate cancer, underwent electrodiagnostic testing. Electrodiagnostic evaluation showed pre-existing peripheral nervous system disorders in three out of four patients. Multiple peripheral nervous system disorders were present in two out of four patients.


CONCLUSIONS
Bortezomib can cause a predominately sensory axonal polyneuropathy. Pre-existing peripheral nervous system disorders, such as neuropathy and radiculopathy, are common in patients with cancer, and may pre-dispose to the development of symptomatic neuronal toxicity when treated with bortezomib. Baseline electrodiagnostic evaluation may identify patients with pre-existing peripheral nervous system disorders at risk for additive neuronal toxicity from neurotoxic chemotherapeutic agents.
Stubblefield
M D
MD
Memorial Sloan-Kettering Cancer Center, Department of Neurology, Rehabilitation Medicine Service, New York, NY 10021, USA. stubblem@mskcc.org
Slovin
S
S
MacGregor-Cortelli
B
B
Muzzy
J
J
Scher
H
H
Wright
J
J
Esseltine
D
D
Schenkein
D
D
O'Connor
O A
OA
D000368:Aged; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D004568:Electrodiagnosis; D005260:Female; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000150:complications / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D010523:Peripheral Nervous System Diseases / Q000175:diagnosis / Q000188:drug therapy*; D011471:Prostatic Neoplasms / Q000150:complications / Q000188:drug therapy; D011480:Protease Inhibitors / Q000627:therapeutic use*; D011719:Pyrazines / Q000627:therapeutic use*
D001897:Boronic Acids; D011480:Protease Inhibitors; D011719:Pyrazines; D000069286:Bortezomib