What is the management of chemotherapy-induced neuropathy?

Management of Chemotherapy-Induced Peripheral Neuropathy

Duloxetine is the only medication with adequate evidence for treating established painful chemotherapy-induced peripheral neuropathy, and no agents are recommended for prevention. 1

Prevention Strategies

No Effective Preventive Agents

• No pharmacologic agents should be used to prevent CIPN based on consistent lack of high-quality evidence demonstrating benefit. 1, 2
• Actively discourage acetyl-L-carnitine for prevention, as evidence shows it may cause harm and worsen neuropathy rather than prevent it. 1, 2

Agents to Avoid for Prevention

Do not offer these agents, as they have been proven ineffective: 1

• Calcium/magnesium infusions (even for oxaliplatin-based regimens) 1
• Amifostine 1, 2
• Amitriptyline 1, 2
• Gabapentin/pregabalin 2
• Glutathione 1
• Vitamin E 1
• Cannabinoids 2
• Metformin 2

Chemotherapy Dose Modification

• Assess appropriateness of dose reduction, dose delay, substitution to non-neurotoxic alternatives, or stopping chemotherapy when patients develop intolerable neuropathy or functional impairment. 1, 2
• This is the only proven strategy to limit progression of CIPN during active treatment. 1

Treatment of Established CIPN

First-Line Pharmacologic Treatment

Duloxetine is the only agent with adequate evidence for treating painful CIPN: 1, 2

• Start at 20 mg orally daily for the first week 2
• Increase to 40 mg daily thereafter 2
• The benefit is limited but represents the best available evidence 1
• Duloxetine showed superior efficacy compared to vitamin B12 for both numbness (p=0.03) and pain (p=0.04) 2

Alternative Pharmacologic Options

When duloxetine is ineffective or not tolerated, consider these agents based on evidence from other neuropathic pain conditions (though CIPN-specific evidence is inconclusive): 1

• Pregabalin: One 2020 trial showed greater improvement compared to duloxetine (93% vs 38%, p<0.001) 2
• Tricyclic antidepressants (such as nortriptyline): Evidence is inconclusive specifically for CIPN but supported for other neuropathic pain 1
• Gabapentin: Inconclusive evidence for CIPN but may be offered given limited alternatives 1
• Compounded topical gel (baclofen, amitriptyline HCL, and ketamine): May be offered based on other neuropathic pain data 1

Non-Pharmacologic Approaches

• Acupuncture as adjunctive therapy: When combined with methylcobalamin (vitamin B12), showed better pain reduction than methylcobalamin alone, suggesting a potential role as adjunctive rather than monotherapy. 2
• Exercise during chemotherapy: Home-based, low-to-moderate walking and resistance exercise can reduce severity and prevalence of CIPN symptoms, especially in older patients. 3
• Photobiomodulation (low-level laser therapy): Considered of moderate benefit based on evidence review. 4

Agents NOT Recommended for Treatment

• Vitamin B12 monotherapy: A placebo-controlled trial found no significant reduction in CIPN incidence (p=0.73), and it was inferior to duloxetine in direct comparison. 2
• Lamotrigine and topical ketamine/amitriptyline (4%/2%): Evidence does not support their use. 4

Clinical Characteristics to Guide Management

Agent-Specific Neuropathy Patterns

• Paclitaxel-induced neuropathy: More prominent in lower limbs during treatment and tends to improve in months following completion. 2
• Oxaliplatin-induced neuropathy: More severe in upper limbs, worsens for 2-3 months after therapy completion (coasting phenomenon), then begins to improve. 2
• Acute oxaliplatin neuropathy: Characterized by cold sensitivity, throat discomfort, difficulty swallowing cold liquids, and muscle cramps peaking 2-3 days post-dose. 1

High-Risk Chemotherapy Agents

The most neurotoxic agents requiring vigilant monitoring include: 2, 3

• Platinum compounds (especially oxaliplatin)
• Taxanes (paclitaxel, docetaxel)
• Vinca alkaloids
• Bortezomib
• Thalidomide

Pre-Treatment Risk Assessment

Before initiating neurotoxic chemotherapy, assess: 2

• Pre-existing neuropathy
• Diabetes mellitus
• Family history of hereditary neuropathies
• Cumulative dose exposure to neurotoxic agents

Common Pitfalls to Avoid

• Do not use gabapentin/pregabalin prophylactically for prevention—they are ineffective and should only be considered for established painful CIPN. 2
• Never use acetyl-L-carnitine for prevention as it may worsen outcomes. 1, 2
• Do not rely solely on motor nerve testing as CIPN predominantly affects sensory nerves with motor function remaining unchanged in most cases. 1
• Recognize the coasting phenomenon with oxaliplatin—neuropathy worsens after treatment stops before improving, so do not assume immediate post-treatment worsening represents treatment failure. 2