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Late Effects

Peripheral Nervous System


Other Drug Related Neuropathy


Taxanes (Paclitaxel)

  • A predominantly sensory/sensorimotor axonal polyneuropathy
  • Dose-limiting toxicity of paclitaxel9
  • Peripheral neuropathy develops in 60% of all patients treated with paclitaxel3
  • In more severely affected patients, autonomic involvement and distal or proximal weakness with myalgias can occur
  • Mechanism:
    • Axonal injury is caused by disruption of microtubule disassembly, resulting in the buildup of large, jumbled microtubule aggregates in dorsal root ganglion neurons, axons, and Schwann cells5
  • Degree of neurotoxicity:
    • Related to the cumulative drug dose and dose intensity, with mild-moderate sensorimotor symptoms at 200 mg/m2, remaining mild until cumulative dose exceeds 1400 mg/m23
  • Symptoms:
    • Can develop 1-3 days after treatment, affecting small fibres the most3
    • Numbness, tingling, burning pain in a stocking-and-glove pattern as first symptom
    • Motor dysfunction, autonomic involvement with high cumulative doses1
  • Investigation
    • Muscle stretch reflexes are diminished
  • Risk factors:
    • Risk increased in:
      • Adults receiving combination chemotherapy (such as adriamycin and cyclophosphamide with the paclitaxel)
      • Patients given prior cisplatin or vincristine
  • Glutamine has been shown to decrease the severity of paclitaxel-associated neuropathic symptoms by upregulating nerve growth factor, though the results have been inconsistent3
  • Progress
    • Generally reversible distal sensory neuropathy. Signs and symptoms may continue to worsen for several weeks after discontinuation of the drug, and then improve gradually.
    • It has been recently found that in patients treated with paclitaxel, 63% did not recover from their symptoms at follow-up1



Thalidomide neuropathy is predominantly a symmetric, length-dependent sensory neuropathy9.

  • Axonal degeneration is seen in the dorsal root ganglion cells and posterior columns with predominant changes being in large nerve fibers
  • Symptoms:
    • Abnormalities of sensory nerve action potentials
    • Painful paresthesias and numbness in a stocking-and-glove distribution
    • Usually no motor weakness
  • Incidence
    • Peripheral neuropathy seen in 20-70% of patients
    • Unlike other chemotherapy-induced peripheral neuropathy, the incidence is associated with daily dose and not cumulative dose
  • Risk factors include gender (female) and age (older)
  • Prognosis:
    • Symptoms and signs resolve very slowly and often incompletely

Thalidomide should be stopped immediately if any symptoms or signs of peripheral neuropathy appear.



Bortezomib causes peripheral sensory neuropathy

  • Dose-limiting toxicity at 1.6 mg/m23
  • Neuropathic symptoms occur in 3-30% of treated patients5, possibly due to impaired mRNA processing and damage to mitochondria and ER in the dorsal root ganglion cells1
  • 10% present with postural hypotension due to autonomic dysfunction10
  • Symptoms:
    • Patients first experience an atypical neuropathic pain syndrome which develops into the typical stocking-and-glove pattern 3
    • Causalgic, burning pain is frequently experienced, as bortezomib primarily affects small fibres (eg heat-sensitive C fibres)5
  • Prognosis:
    • 80% of patients recover within 3-4 months, but a small percentage remains severely affected with limited and prolonged recovery10



High dose IV Cytarabine can occasionally be associated with peripheral neuropathy.

Can present with:

  • Distal sensorimotor polyneuropathy
  • Brachial plexopathy
  • Rarely, a rapidly progressive, severe ascending demyelinating motor neuropathy resembling Guillain-Barre syndrome



Rarely causes peripheral neuropathy with:

  • Distal pain
  • numbness
  • Weakness that partially resolves after discontinuation of the drug



High dose Ifosfamide can induce rapid worsening of a pre-existing mild chemotherapy-related axonal polyneuropathy





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