Chemotherapy-Induced Peripheral Neuropathy

Chemotherapy induced peripheral neuropathy is a dose dependent, mostly sensory and length dependent neuropathy from neurotoxic cancer drugs. It affects about 30 to 70% of patients, and persists for 6 months or more in about 30%. Causative drugs are platinum agents (cisplatin, oxaliplatin, carboplatin), taxanes (paclitaxel, docetaxel), vinca alkaloids (vincristine), proteasome inhibitors (bortezomib) and thalidomide.

Pathophysiology. Drugs damage dorsal root ganglia (platinum), microtubules (taxanes, vinca) or mitochondria, and alter ion channels (oxaliplatin acute cold induced symptoms).

Numbness, tingling and pain in a stocking and glove pattern, loss of vibration and proprioception, reduced ankle reflexes and balance problems. Oxaliplatin causes acute cold triggered paraesthesia and pharyngolaryngeal dysaesthesia. Vincristine may cause foot drop, jaw pain, constipation and autonomic neuropathy. Platinum neuropathy can progress for weeks after "coasting".

Red flags.

• Rapidly progressive weakness or severe pain.
• Autonomic failure or ileus (vincristine).

Diagnosis is clinical, from the temporal relationship to treatment. Grade severity. Nerve conduction studies show axonal sensory neuropathy. Exclude other causes: diabetes, vitamin B12 deficiency, thyroid disease, alcohol, paraneoplastic neuropathy, nerve compression or spinal metastases, and hereditary neuropathy (vincristine severity is greater in Charcot-Marie-Tooth disease).

Differential diagnosis.

• Paraneoplastic neuropathy, spinal cord or root compression.
• Diabetic, nutritional and hereditary neuropathy.
• Immune checkpoint inhibitor neuropathy and chemotherapy induced myopathy.

Prevention and dose modification. Reduce, delay or stop the culprit drug for disabling (grade 2 or higher) neuropathy, in discussion with oncology. Cryotherapy and compression of the hands and feet reduce taxane neuropathy. No drug reliably prevents it.

Painful neuropathy. Duloxetine 30 mg daily for 1 week, then 60 mg daily (the only agent with supporting evidence), then gabapentin 300 mg daily, increased to 600 to 1200 mg three times daily (adjust to eGFR) or pregabalin 75 to 300 mg twice daily, amitriptyline 10 to 75 mg at night, and topical capsaicin or lidocaine. Opioids only if needed.

Function and safety. Exercise and balance training, physiotherapy, occupational therapy, footwear review and falls prevention. Acupuncture may help.

Avoid vitamin supplements and calcium magnesium infusions as proven prevention.

Monitoring. Symptom scores at each cycle, and function after treatment.

Referral and escalation. Refer to oncology and neurology, and to pain services if refractory.