Bortezomib-induced peripheral neuropathy in multiple myeloma: a comprehensive review of the literature

Argyriou, Andreas A.; Iconomou, Gregoris; Kalofonos, Haralabos P.

doi:10.1182/blood-2008-04-149385

Cited by 371 publications

(308 citation statements)

References 52 publications

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“…In our study cohort, 88% of myeloma patients treated with subcutaneous bortezomib developed clinical signs of neuropathy of any grade which led in 16% to prolongation of treatment intervals or discontinuation of bortezomib treatment. The majority of the patients had sensory deficits which is consistent with previous reports on bortezomib inducing a dose-related peripheral, mainly sensory polyneuropathy with accompanying neuropathic pain (Argyriou et al, 2008;Delforge et al, 2010;Keller et al, 2015;Koeppen et al, 2014;Mohty et al, 2010;Richardson et al, 2006). Thus, optimized concepts for the prevention and treatment of bortezomib induced CIPN are obviously essential for myeloma patients, and such strategies involve subcutaneous application, the once weekly administration, and timely discontinuation at early signs of neuropathy to enable reversibility of symtoms (Argyriou et al, 2008;Cavaletti et al, 2010;Stubblefield et al, 2009).…”

Section: Discussionsupporting

confidence: 79%

“…However, chemotherapy-induced polyneuropathy (CIPN) is a major and often limiting side effect of bortezomib (Argyriou et al, 2008;Delforge et al, 2010;Keller et al, 2015;Koeppen et al, 2014;Mohty et al, 2010;Richardson et al, 2006). In our study cohort, 88% of myeloma patients treated with subcutaneous bortezomib developed clinical signs of neuropathy of any grade which led in 16% to prolongation of treatment intervals or discontinuation of bortezomib treatment.…”

Section: Discussionmentioning

confidence: 94%

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Stem cell mobilization chemotherapy with gemcitabine is effective and safe in myeloma patients with bortezomib-induced neurotoxicity

Mueller

Keller

Seipel

et al. 2015

Leukemia & Lymphoma

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Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 94%

Stem cell mobilization chemotherapy with gemcitabine is effective and safe in myeloma patients with bortezomib-induced neurotoxicity

Mueller

Keller

Seipel

et al. 2015

Leukemia & Lymphoma

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“…Another possible explanation comes from studies of bortezomib action in cancerous cells, suggesting that its neurotoxicity might be a side effect of blocking NF‐kB activation and subsequent inhibition of nerve growth factors required for neuronal survival. Finally, there is a body of evidence suggesting that bortezomib neurotoxicity might be triggered by inflammatory processes concomitant with neoplastic growth (Argyriou, Iconomou, & Kalofonos, 2008; Meregalli, 2015). Surprisingly, studies showed that cancer therapy involving both bortezomib and thalidomide reduced incidence of chemotherapy‐induced neuropathies in cancer patients, suggesting that both substances might cancel each other's neurotoxic activity in the course of treatment (Chaudhry, Cornblath, Polydefkis, Ferguson, & Borrello, 2008).…”

Section: Bortezomibmentioning

confidence: 99%

Chemotherapy‐induced neuropathies—a growing problem for patients and health care providers

2016

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IntroductionChemotherapy‐induced neuropathies are one of the most common side effects of cancer treatment, surpassing bone marrow suppression and kidney dysfunction. Chemotherapy effects on the nervous system vary between different classes of drugs and depend on specific chemical and physical properties of the drug used. The three most neurotoxic classes of anti‐cancer drugs are: platinum‐based drugs, taxanes, and thalidomide and its analogs; other, less neurotoxic but also commonly used drugs are: bortezomib, ixabepilone, and vinca alkaloids.MethodsHere, in this paper, based on our experience and current knowledge, we provide a short review of the most common, neuropathy‐inducing anti‐cancer drugs, describe the most prevalent neuropathy symptoms produced by each of them, and outline preventive measures and treatment guidelines for cancer patients suffering from neuropathy and for their health care providers.ResultsPatients should be encouraged to report any signs of neuropathic pain, alteration in sensory perception, tingling, numbness, burning, increased hot/cold sensitivity and motor dysfunctions as early as possible. If known neurotoxic chemotherapeutics are used, a neurological examination with electrophysiological evaluation should be implemented early in the course of treatment so, both patients and physicians would be better prepared to cope with possible neurotoxic effects.ConclusionsThe use of neurotoxic chemotherapeutics should be closely monitored and if clinically permitted, that is, if a patient shows signs of cancer regression, drug doses should be reduced or combined with other less neurotoxic anti‐cancer medication. If not counteractive, the use of over the counter antineuropathic supplements such as calcium or magnesium might be encouraged. If physically possible, patients should also be encouraged to exercise regularly and avoid factors that might increase nerve damage such as excessive drinking, smoking, or sitting in a cramped position.

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“…Currently, only broad-acting proteasome inhibitors are in clinical use. Proteasome inhibitors bortezomib (Velcade) and carfilzomib (Kyprolis) have reached phase II clinical trials for use in mantle cell lymphoma (MCL) and multiple myeloma (9)(10)(11)(12), although use is associated with peripheral neuropathy (12,13). The E3 ligase modulator Lenalidomide (Revlimid, an analogue of Thalidomide), is also used in treatment of multiple myeloma but has associated resistance and toxicity (14).…”

Section: Ubiquitination and The Role Of E3 Ubiquitin Ligasesmentioning

confidence: 99%

Functional Roles of the E3 Ubiquitin Ligase UBR5 in Cancer

Shearer

Iconomou

Watts

et al. 2015

Molecular Cancer Research

106

141

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The Ubiquitin-Proteasome System (UPS) is an important regulator of cell signaling and proteostasis, which are essential to a variety of cellular processes. The UPS is disrupted in many diseases including cancer, and targeting the UPS for cancer therapy is gaining wide interest. E3 ubiquitin ligases occupy a key position in the hierarchical UPS enzymatic cascade, largely responsible for determining substrate specificity and ubiquitin (Ub) chain topology. The E3 ligase UBR5 (aka EDD1) is emerging as a key regulator of the UPS in cancer and development. UBR5 expression is deregulated in many cancer types and UBR5 is frequently mutated in mantle cell lymphoma. UBR5 is highly conserved in metazoans, has unique structural features, and has been implicated in regulation of DNA damage response, metabolism, transcription, and apoptosis. Hence, UBR5 is a key regulator of cell signaling relevant to broad areas of cancer biology. However, the mechanism by which UBR5 may contribute to tumor initiation and progression remains poorly defined. This review synthesizes emerging insights from genetics, biochemistry, and cell biology to inform our understanding of UBR5 in cancer. These molecular insights indicate a role for UBR5 in integrating/coordinating various cellular signaling pathways. Finally, we discuss outstanding questions in UBR5 biology and highlight the need to systematically characterize substrates, and address limitations in current animal models, to better define the role of UBR5 in cancer.

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Bortezomib-induced peripheral neuropathy in multiple myeloma: a comprehensive review of the literature

Cited by 371 publications

References 52 publications

Stem cell mobilization chemotherapy with gemcitabine is effective and safe in myeloma patients with bortezomib-induced neurotoxicity

Stem cell mobilization chemotherapy with gemcitabine is effective and safe in myeloma patients with bortezomib-induced neurotoxicity

Chemotherapy‐induced neuropathies—a growing problem for patients and health care providers

Functional Roles of the E3 Ubiquitin Ligase UBR5 in Cancer

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