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Late Effects

Peripheral Nervous System


Vincristine Related Neuropathy


Vincristine neuropathy:

  • Distal symmetric sensory and motor neuropathy6
  • Generally begins 4-5 weeks after treatment start
  • Impaired ankle jerks can be seen as early as 2 weeks following onset of therapy
  • This neurotoxicity is very common, affecting 70-90% of all patients3 given this drug

Vincristine more frequently causes severe peripheral neuropathy than other vinca alkaloids (vinblastine, vindesine)1.

Vinblastine can also cause peripheral neuropathy. Peripheral neuropathy is rarely caused by vinblastine.

A distal dose-dependent axonal sensorimotor polyneuropathy has been described after treatment with vinorelbine.



  • Vinca alkaloids disrupt microtubule formation and axoplasmic transport which leads to axonal degeneration and neuropathy of peripheral nerve fibres5


Signs and Symptoms:

First symptoms are usually paresthesias in the fingers and feet, and loss of ankle jerks.



 Paresthesias (57% of patients)3

    • Initially in fingers, followed by feet
    • Impaired vibration sense
    • Proprioception is spared


Wrist and foot “drop”6


Neuritic pain and muscle cramps


Autonomic symptoms (constipation, ileus) in up to 33% of patients.5


Loss of deep tendon reflexes (absent ankle jerks6) (22-34% of patients)3


Motor weakness involving:

  • Extensor muscles of the fingers
  • Wrists
  • Toes and dorsiflexors of the feet.


Less frequently causes:

    • Paralytic ileus
    • Postural hypotension
    • Cranial nerve palsies
      • Bilateral ptosis (commonest cranial problem)
    • Transient cortical blindness
    • Oculomotor nerve dysfunction
      • paralytic strabismus
    • Jaw pain
    • Facial palsy
    • Sensorineural hearing loss
    • Laryngeal nerve paresis (hoarseness)





EMG studies show:

  • Denervation with fibrillation
  • Reduced amplitude of sensory nerve potentials and prolonged distal motor latencies with normal or mildly slowed conduction velocities, indicating a primary axonal degeneration
  • Decreased numbers of motor units in the distal muscles


 Risk Factors:

  • Incidence and severity of symptoms is related to the cumulative dose:
    • Peripheral neuropathy in vincristine treatment is seen when the cumulative dose rises above 6 mg/m2
    • Significant toxicities occur above 15-20 mg total3
  • Severe Vincristine related neuropathy associated with:
    • Underlying peripheral neuropathy
    • Patients with type 1 Charcot-Marie-Tooth hereditary neuropathy can develop rapidly progressive, severe neuropathy after low cumulative doses of vincristine7
    • Bedridden patients
    • Hepatic insufficiency
    • Administration of concurrent granulocyte- or granulocyte-macrophage-colony stimulating factor



  • Slowly reversible upon removal of the drug.  Symptoms may worsen for a few months after vincristine is discontinued, and then improve slowly.
    • Usually mostly resolved 4 months or so after the end of therapy, but may take up to 2 years
  • Charcot-Marie-Tooth can be associated with a severe exacerbation after Vincristine therapy6
  • Drop foot can be prevented in bedridden patients with the use of bilateral foot braces to keep the foot dorsiflexed6


If vincristine therapy continues, sensory symptoms in the limbs progress proximally and distal weakness occurs in more severely affected cases6.

Neurotoxicity is the dose limiting toxicity of vincristine3



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