Chemotherapy

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.