title: Neurological adverse effects caused by cytotoxic and targeted therapies.
abstract: Historically, body tissues with a high rate of cell turnover, such as the bone marrow, have been most susceptible to chemotherapy-induced damage. The widespread use of hematopoietic colony-stimulating factors, as well as the development of new agents, has led to improved outcomes in many types of cancer. As a consequence, neurotoxicity has become increasingly important as a cause of dose-limiting chemotherapy toxicity. An understanding of the neurologic complications of these new agents is crucial in order to prevent irreversible neurologic injury. Moreover, chemotherapy complications that require discontinuation of a potentially effective drug need to be distinguished from other causes of neurotoxicity including the tumor itself, paraneoplasia, radiation and surgery, which may require a different therapeutic strategy. We review the prevalence, prevention, and management of important and unusual neurotoxicities related to chemotherapy and targeted agents approved by the FDA since January 1999. These agents include DNA-damaging agents such as oxaliplatin and temozolomide, microtubule poisons like ixabepilone, proteasome inhibitors (bortezomib), and signal transduction inhibitors such as imatinib, sunitinib and bevacizumab.
authors.affiliation: Department of Neurology, University of Virginia in Charlottesville, VA 22908-0432, USA. davidschiff@virginia.edu
authors.forename: David
authors.initials: D
authors.lastname: Schiff
authors.forename: Patrick Y
authors.initials: PY
authors.lastname: Wen
authors.forename: Martin J
authors.initials: MJ
authors.lastname: van den Bent
mesh_terms: D020533:Angiogenesis Inhibitors / Q000009:adverse effects; D000911:Antibodies, Monoclonal / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000009:adverse effects*; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects; D001549:Benzamides; D000068258:Bevacizumab; D001897:Boronic Acids / Q000009:adverse effects; D000069286:Bortezomib; D002986:Clinical Trials as Topic; D003606:Dacarbazine / Q000009:adverse effects / Q000031:analogs & derivatives; D017277:Drug Approval; D034261:Epothilones / Q000009:adverse effects; D006801:Humans; D000068877:Imatinib Mesylate; D007211:Indoles / Q000009:adverse effects; D009369:Neoplasms / Q000188:drug therapy*; D020258:Neurotoxicity Syndromes / Q000209:etiology*; D009944:Organoplatinum Compounds / Q000009:adverse effects; D000077150:Oxaliplatin; D010879:Piperazines / Q000009:adverse effects; D011719:Pyrazines / Q000009:adverse effects; D011743:Pyrimidines / Q000009:adverse effects; D011758:Pyrroles / Q000009:adverse effects; D000077210:Sunitinib; D000077204:Temozolomide; D050257:Tubulin Modulators / Q000009:adverse effects; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D001549:Benzamides; D001897:Boronic Acids; D034261:Epothilones; D007211:Indoles; D009944:Organoplatinum Compounds; D010879:Piperazines; D011719:Pyrazines; D011743:Pyrimidines; D011758:Pyrroles; D050257:Tubulin Modulators; D000077150:Oxaliplatin; D000068258:Bevacizumab; D000069286:Bortezomib; D003606:Dacarbazine; D000068877:Imatinib Mesylate; C430592:ixabepilone; D000077210:Sunitinib; D000077204:Temozolomide
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