The Massachusetts General Hospital Handbook of Neurology

Authors: Flaherty, Alice W.; Rost, Natalia S.

Title: Massachusetts General Hospital Handbook of Neurology, The, 2nd Edition

Copyright 2007 Lippincott Williams & Wilkins

> Table of Contents > Drugs > Chemotherapy

Chemotherapy

A. Neurological complications of cancer

Metastases; encephalopathy (metabolic, drug, or radiation induced), paraneoplastic syndromes, CNS infection, infarct or bleed, myopathy (steroid-induced, cachectic), myositis, myasthenic syndromes.

B. Neurological side effects of chemotherapy by class

• Alkylating agents:

  • Nitrogen mustards: Cyclophosphamide, melphalan, chlorambucil. Neuro side effects rare.

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  • Nitrosoureas: Lomustine (CCNU), carmustine (BCNU). BCNU causes leukoencephalopathy at high doses. CCNU causes blindness in combination with cranial irradiation.

• Antimetabolites:

  • Folate analogs: Methotrexate:

    • Acute transient chemical meningitis: 4-6 h after intrathecal dose, in ~10% of pts.

    • Transient encephalopathy: 7-10 d after third or fourth intrathecal dose, in ~4% of pts.

    • Transverse myelopathy: After intrathecal dose, uncommon; paraplegia often permanent.

    • Leukoencephalopathy: Weeks or months after brain XRT plus intrathecal or high-dose IV methotrexate.

  • Pyrimidine analogs: 5-Fluorouracil, cytarabine. Occasional transient cerebellar dysfunction. Cytarabine can cause neuropathy.

• Purine analogs: Azathioprine, fludarabine. Avoid allopurinol.

  Table 47. Antineoplastic agent side effects.

  Neuro Heart Liver GI Vasc Lung Renal GU Azathioprine     X X         Bleomycin       X   X     Busulfan           X     Carboplatin X               Carmustine (BCNU) X   X X   X X   Cisplatin (CDDP) X           X X Cyclophosphamide   X             Cytarabine (Ara-C) X     X         Dacarbazine (DTIC)       X         Doxorubicin (Adria.)   X   X X       Etoposide (VP-16) X               Fluorouracil (5-FU)       X         Ifosfamide   X X         X Methotrexate     X X   X X   Mitomycin C       X X X     Taxol X X             Temozolomide       X         Vinblastine X       X       Vincristine X       X

• Natural products:

  • Vinca alkaloids: Vincristine, vinblastine. Especially vincristine: peripheral nerve dysfunction, usually hours to days after dose, usually reversible. Worse if liver dz. See autonomic dysfunction and

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    ileus (metoclopramide can help), decreased reflexes, toe and finger paresthesias, weak foot and wrist.

  • Abx: Daunorubicin, doxorubicin, bleomycin, mitomycin. Neuro effects rare.

  • Other: Etoposide, L-asparaginase. L-asparaginase causes encephalopathy, usually transient, in ~15% of pts.; also stroke or cerebral bleed in ~2% (drug-induced coagulopathy).

• Hormonal agents: Tamoxifen, flutamide, leuprolide. Neurological side effects rare.

• Other: Cisplatin, hydroxyurea, procarbazine, mitotane, aminoglutethimide. Cisplatin (but not carboplatin) causes hearing loss, dose-dependent large-fiber sensory neuropathy; sx can progress even after drug stopped. Sometimes seizures, confusion (but r/o Mg and Ca wasting). Procarbazine can cause encephalopathy and peripheral neuropathy.

• Antineoplastic agent side effects: See Table 47.