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Neurological adverse effects caused by cytotoxic and targeted therapies

Nature Reviews Clinical Oncology volume 6, pages 596–603 (2009)Cite this article

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.

Key Points

  • Peripheral neuropathy often represents the dose-limiting toxicity for thalidomide, bortezomib, Abraxane®, ixabepilone, and oxaliplatin

  • Sensory neuropathy from microtubule poisons typically recovers quickly after drug discontinuation; however, neuropathy from oxaliplatin and bortezomib improves more slowly (over several months), and recovery from thalidomide neuropathy is variable and incomplete

  • The addition of temozolomide to fractionated radiotherapy is associated with an increased risk of peritumoral contrast enhancement and vasogenic edema, attributed to blood–brain barrier breakdown that mimics early tumor progression

  • Among the new purine and pyrimidine analogs, nelarabine commonly produces peripheral neuropathy and encephalopathy, and liposomal cytarabine routinely causes arachnoiditis warranting corticosteroid prophylaxis

  • Muscle cramps and myalgias frequently arise in patients receiving imatinib and generally respond to supportive measures; rhabdomyolysis is rarely seen

  • All drugs that target the VEGF pathway convey a small risk of producing reversible posterior encephalopathy syndrome, probably because they all are capable of producing hypertension

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Figure 1: Pseudoprogression from radiation and temozolomide: a 69-year-old woman presented with right-sided weakness and underwent stereotactic biopsy of a left frontal mass that demonstrated glioblastoma.
Figure 2: Imatinib-associated hemorrhage: a 45-year-old man with grade 2 oligoastrocytoma who had failed radiation and temozolomide was placed on a clinical trial of imatinib.

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  1. Departments of Neurology, Neurological Surgery, and Medicine, University of Virginia in Charlottesville, VA, USA

    David Schiff

  2. Division of Neuro-Oncology, Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA

    Patrick Y. Wen

  3. Daniel den Hoed Cancer Center at Erasmus University Hospital in Rotterdam, The Netherlands

    Martin J. van den Bent

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D. Schiff is a Consultant for Genentech and Schering-Plough and he receives grant/research support from Genentech. P. Wen receives grant/research support from Genentech. M. van den Bent is a Consultant and receives grant/research support from Roche and Schering-Plough; he is also on the Speakers bureau for Schering-Plough.

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Schiff, D., Wen, P. & van den Bent, M. Neurological adverse effects caused by cytotoxic and targeted therapies. Nat Rev Clin Oncol 6, 596–603 (2009). https://doi.org/10.1038/nrclinonc.2009.128

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