Peripheral Neuropathy with CAPOX in Rectal Cancer Treatment
Yes, CAPOX (capecitabine and oxaliplatin) therapy for rectal cancer commonly causes peripheral neuropathy, primarily due to the oxaliplatin component, with up to 94% of patients experiencing acute neuropathy symptoms during treatment. 1
Mechanism and Presentation of Oxaliplatin-Induced Neuropathy
Oxaliplatin causes two distinct forms of peripheral neuropathy:
Acute Neuropathy
- Occurs within hours or 2 days following a dose
- Resolves within 14 days but frequently recurs with further dosing
- Presents as transient paresthesia, dysesthesia, and hypoesthesia in hands, feet, perioral area, or throat
- Can include jaw spasm, abnormal tongue sensation, dysarthria, eye pain, and chest pressure
- Occurs in approximately 56% of patients receiving oxaliplatin-containing regimens 2
- Cold sensitivity is a hallmark symptom - exposure to cold temperatures or objects can precipitate or exacerbate symptoms 2
Delayed/Chronic Neuropathy
- Persists for more than 14 days
- Characterized by paresthesias, dysesthesias, and hypoesthesias
- May include deficits in proprioception affecting daily activities (writing, buttoning, swallowing, walking)
- Occurs in approximately 48% of patients receiving oxaliplatin 2
- May develop without prior acute neuropathy
- Can persist long after treatment completion 3
Incidence and Severity
The severity of peripheral neuropathy with CAPOX varies:
- In adjuvant setting: Grade 1 (44%), Grade 2 (35%), Grade 3 (16%) 1
- In palliative setting: Grade 1 (54%), Grade 2 (32%), Grade 3 (3%), Grade 4 (1%) 1
Chronic neuropathy persists in:
- 57% of adjuvant patients at 6 months and 35% at 12 months
- 18% of palliative patients at 6 months and 16% at 12 months 1
Risk Factors and Monitoring
The primary risk factor for developing chronic peripheral neuropathy is cumulative oxaliplatin dose 1. Patients should be monitored for:
- Cold sensitivity
- Tingling in hands and feet
- Numbness in extremities
- Trouble with balance
- Nerve pain
- Muscle or joint aches 4
Management Recommendations
Consider oxaliplatin discontinuation after 3 months of therapy (or sooner for unacceptable neurotoxicity) while maintaining other drugs in the regimen until tumor progression 3
Implement a "stop-and-go" approach with oxaliplatin-free intervals to decrease neurotoxicity without affecting overall survival 3
Do not use calcium/magnesium infusions for prevention of oxaliplatin-related neurotoxicity as data are insufficient to support this practice 3
For symptomatic treatment of neuropathic pain:
Avoid topical application of ice for mucositis prophylaxis or other conditions as cold temperature can exacerbate acute neurological symptoms 2
Monitor closely for early signs of neuropathy to allow for prompt dose adjustments 3
Important Considerations
Patients should not receive subsequent oxaliplatin therapy until near-total resolution of neurotoxicity 3
The CONcePT trial found that intermittent oxaliplatin approach improved acute peripheral sensory neuropathy (P=0.037) over continuous oxaliplatin 3
While capecitabine alone has rarely been associated with peripheral neuropathy 6, the combination with oxaliplatin in CAPOX significantly increases this risk
Hand-foot syndrome (primarily from capecitabine) and peripheral neuropathy are major contributors to dose reduction (9.6%), treatment delay (5.4%), and drug discontinuation (6.1%) in patients receiving CAPOX 7
Some patients may develop neuropathy symptoms after CAPOX completion despite having no symptoms during treatment 1
By understanding these patterns of neuropathy and implementing appropriate monitoring and management strategies, clinicians can optimize treatment outcomes while minimizing the impact of this common adverse effect on patients' quality of life.