Bortezomib-induced peripheral neuropathy in multiple myeloma: a comprehensive review of the literature.
Bortezomib has demonstrated significant activity in clinical trials, mainly against recurrent or newly diagnosed multiple myeloma (MM). Peripheral neuropathy is a significant toxicity of bortezomib, requiring dose modification and potential changes in the treatment plan when it occurs. The mechanism underlying bortezomib-induced peripheral neuropathy (BIPN) is 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 recognized that BIPN may be a proteasome inhibitor class effect, producing primarily a small fiber and painful, axonal, sensory distal neuropathy. Incidence of BIPN is mainly related to various risk factors, including cumulative dose and evidence of preexisting neuropathy. Assessment of BIPN is based primarily on neurologic clinical examination and neurophysiologic methods. 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 success. This review looks critically at the pathogenesis, incidence, risk factors, diagnosis, characteristics, and management of BIPN, and highlights areas for future research.
Department of Neurology, Saint Andrew's General Hospital of Patras, Greece.
Andreas A
AA
Argyriou
Gregoris
G
Iconomou
Haralabos P
HP
Kalofonos
D000970:Antineoplastic Agents / Q000009:adverse effects*; D001897:Boronic Acids / Q000009:adverse effects*; D000069286:Bortezomib; D004594:Electrophysiology; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000175:diagnosis / Q000503:physiopathology / Q000517:prevention & control; D011480:Protease Inhibitors / Q000009:adverse effects*; D011719:Pyrazines / Q000009:adverse effects*; D012307:Risk Factors
D000970:Antineoplastic Agents; D001897:Boronic Acids; D011480:Protease Inhibitors; D011719:Pyrazines; D000069286:Bortezomib