Peripheral Nervous System
Other Drug Related Neuropathy
- 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
- Risk increased in:
- 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
