Submitted April 1, 2008
Accepted June 2, 2008
Bortezomib-induced peripheral neuropathy in multiple myeloma: a comprehensive review of the literature
Andreas A. Argyriou, Gregoris Iconomou, and Haralabos P. Kalofonos*
Department of Neurology, Saint Andrew's General Hospital of Patras, Patras, Greece
Department of Medicine-Division of Oncology, University of Patras Medical School, Patras, Greece
* Corresponding author; email: kalofon{at}med.upatras.gr.
Bortezomib, a novel proteosome inhibitor, has demonstrated significant activity in clinical trials mainly against recurrent or newly diagnosed multiple myeloma (MM). Peripheral neuropathy is a significant toxicity of bortezomib, which when it occurs requires dose modification and potential changes in the treatment plan.
The mechanism underlying the bortezomib-induced peripheral neuropathy (BIPN) is still unknown. Metabolic changes resulting from the accumulation of bortezomib in the dorsal root ganglia cells, mitochondrial-mediated disregulation of Ca++ homeostasis and disregulation of neurotrophins may contribute to the pathogenesis of BIPN. It is increasingly recognised that BIPN may well be a proteosome inhibitor class effect and this produces primarily a small fiber and painful, axonal, sensory distal neuropathy, usually with sparing of the motor function.
The incidence of BIPN is mainly related to various risk factors, including cumulative dose and evidence of pre-existing neuropathy. The assessment of BIPN is primarily based on neurologic clinical examination and neurophysiological methods, such as nerve conduction study and quantitative sensory testing.
To date, apart from the use of dose reduction and schedule change algorithm, there is no effective treatment with neuroprotective agents for BIPN. Analgesics, tricyclic antidepressants, anticonvulsants and vitamin supplements have been used as symptomatic treatment against bortezomib-associated neuropathic pain with some measure of success.
This review critically looks at the pathogenesis, incidence, risk factors, diagnosis, characteristics and management of BIPN. We also highlight areas of future research to pursue.
