What are the approved medications for chemotherapy-induced peripheral neuropathy (CIPN)?

Management of Chemotherapy-Induced Peripheral Neuropathy

Duloxetine is the only FDA-approved medication for the treatment of chemotherapy-induced peripheral neuropathy (CIPN) pain. 1

Understanding CIPN

CIPN is a common adverse effect of many chemotherapeutic agents, particularly:

• Taxanes (paclitaxel)
• Platinum drugs (oxaliplatin, cisplatin)
• Vinca alkaloids
• Bortezomib
• Epothilones
• Eribulin

CIPN typically presents as:

• Symmetric, distal, length-dependent "glove and stocking" distribution
• Predominantly sensory symptoms rather than motor
• Dose-dependent symptoms
• Sensory axonal damage with reduced amplitude of sensory nerve action potentials

Prevention of CIPN

Based on current evidence, no agents are recommended for the prevention of CIPN 1. In fact:

• Acetyl-L-carnitine should be actively discouraged for CIPN prevention due to potential harm 1
• The following agents should NOT be used for prevention:
  • All-trans retinoic acid
  • Amifostine
  • Amitriptyline
  • Calcium magnesium
  • Calmangafodipir
  • Cannabinoids
  • Carbamazepine
  • L-carnosine
  • Diethyldithiocarbamate (DDTC)
  • Gabapentin/pregabalin
  • Glutamate
  • Glutathione (for paclitaxel/carboplatin chemotherapy)
  • Goshajinkigan (GJG)
  • Metformin

Treatment of Established CIPN

First-Line Treatment:

• Duloxetine (60 mg daily) is the only agent with sufficient evidence to support its use for painful CIPN 1, 2
  • Start at 30 mg daily for one week, then increase to 60 mg daily
  • May be more effective for oxaliplatin-induced than paclitaxel-induced neuropathy
  • Taper slowly when discontinuing to avoid withdrawal symptoms
  • Provides moderate benefit for pain control

Alternative Options (Limited Evidence):

While not formally recommended due to inconclusive evidence, the following may be considered when duloxetine is ineffective or contraindicated:

1. Tricyclic antidepressants (e.g., nortriptyline) 1

   • Use with caution, especially in elderly patients due to potential toxicity
   • Limited evidence specifically for CIPN

2. Gabapentinoids (gabapentin, pregabalin) 1

   • One negative trial exists for gabapentin in CIPN
   • May be considered based on efficacy in other neuropathic pain conditions

3. Topical compounded gel containing baclofen (10 mg), amitriptyline HCL (40 mg), and ketamine (20 mg) 1

   • Limited availability (requires compounding pharmacy)
   • Long-term safety not established

Emerging Therapies with Preliminary Evidence:

The following therapies show promise but require further research:

• Scrambler therapy 1
• Acupuncture 1, 3
• Exercise therapy 1, 4
• Photobiomodulation/low-level laser therapy 3

Management of Chemotherapy During CIPN

When patients develop CIPN during chemotherapy, clinicians should:

• Assess the appropriateness of dose delaying, dose reduction, or stopping chemotherapy 1
• Consider substituting with agents that do not cause CIPN
• Weigh the benefits of continuing chemotherapy against the risk of worsening neuropathy and functional impairment

Clinical Pearls

• CIPN can be a dose-limiting toxicity that may require chemotherapy modification
• Regular assessment of CIPN symptoms during chemotherapy is essential
• Duloxetine provides modest benefit but is currently the best-supported pharmacological option
• The benefit-risk profile should be carefully considered for each patient
• Patients should be educated about potential CIPN symptoms and the importance of early reporting

Common Pitfalls

• Failing to recognize CIPN early, leading to severe symptoms
• Using medications without sufficient evidence for CIPN (e.g., acetyl-L-carnitine)
• Abruptly discontinuing duloxetine (should be tapered)
• Overlooking non-pharmacological approaches that may provide benefit
• Not considering chemotherapy dose modifications when CIPN becomes severe

Remember that while several treatments are being investigated, duloxetine remains the only agent with sufficient evidence to recommend for CIPN treatment.