Treatment of Chemotherapy-Induced Peripheral Neuropathy
Duloxetine is the only agent with sufficient evidence to support its use for the treatment of painful chemotherapy-induced peripheral neuropathy (CIPN). 1
Understanding CIPN
Chemotherapy-induced peripheral neuropathy is a common adverse effect of several cytotoxic drugs, including:
- Taxanes (paclitaxel, docetaxel)
- Platinum compounds (cisplatin, oxaliplatin)
- Vinca alkaloids
- Bortezomib
- Thalidomide
- Epothilones
- Eribulin
CIPN typically presents with a symmetric, distal, length-dependent "glove and stocking" distribution, predominantly affecting sensory rather than motor function. Symptoms may include:
- Numbness and tingling
- Pain (burning, shooting, electric-like)
- Temperature sensitivity (especially with oxaliplatin)
- Reduced vibration and position sense
- Motor weakness (less common)
- Autonomic dysfunction (rare)
Treatment Algorithm for CIPN
1. During Active Chemotherapy
- Assess severity and functional impact of neuropathy symptoms
- Consider dose modification strategies when neuropathy becomes intolerable or causes functional impairment 1:
- Dose delay
- Dose reduction
- Substitution with non-neurotoxic agents
- Discontinuation of the neurotoxic agent
2. For Established Painful CIPN
First-line treatment:
- Duloxetine 30mg daily for one week, then increase to 60mg daily 1
- This is the only agent with moderate-quality evidence supporting its efficacy
- Note that the benefit is modest but clinically meaningful
Alternative options (limited evidence):
For patients who do not respond to or cannot tolerate duloxetine:
- Tricyclic antidepressants (e.g., nortriptyline)
- Gabapentin or pregabalin
- Topical gel containing baclofen, amitriptyline HCL, and ketamine
These alternatives may be offered based on their efficacy in other neuropathic pain conditions, despite limited evidence specifically for CIPN 1.
3. Non-Pharmacological Approaches (Limited Evidence)
The following may be considered as adjuncts to pharmacological treatment, though evidence is preliminary:
- Exercise therapy (low-to-moderate walking and resistance exercise)
- Acupuncture
- Scrambler therapy
Important Considerations and Pitfalls
Prevention strategies are ineffective
- No agents are recommended for CIPN prevention
- Acetyl-L-carnitine should be specifically avoided as it may worsen CIPN 1
Monitoring is crucial
- Regular assessment of symptoms and functional impact
- Early intervention when symptoms develop
Common pitfalls to avoid:
- Delaying dose modifications when significant neuropathy develops
- Using unproven preventive agents that may cause harm
- Failing to recognize that symptoms may worsen even after chemotherapy discontinuation (coasting phenomenon)
- Overlooking the impact of CIPN on quality of life and daily functioning
Patient education:
- Inform patients about potential CIPN symptoms before starting neurotoxic chemotherapy
- Encourage early reporting of symptoms
- Set realistic expectations about treatment efficacy and potential persistence of symptoms
Special Considerations
- Pre-existing neuropathy: Patients with diabetes, alcohol use disorder, or other causes of neuropathy are at higher risk for developing severe CIPN 1
- Elderly patients: May benefit more from exercise interventions during chemotherapy 2
- Platinum agents: Particularly oxaliplatin has the highest prevalence of CIPN 3
In conclusion, management of CIPN remains challenging with limited effective options. Duloxetine is the only treatment with moderate evidence of efficacy, while dose modification during chemotherapy is an important strategy to prevent worsening neuropathy when symptoms become intolerable.