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Peripheral neuropathy exacerbation associated with topical 5-fluorouracil
Muhammad Wasif Saif1, Shahrukh Hashmi, Lori Mattison
1Section of Medical Oncology, Yale Cancer Center, Yale University School of Medicine, New Haven, Connecticut 06520, USA. wasif.saif@yale.edu
Anti-Cancer Drugs
|September 27, 2006
Summary
Topical 5-fluorouracil (Efudex) can worsen peripheral neuropathy, even with normal enzyme levels. Discontinuation of the drug resolved symptoms, suggesting a causal link for this adverse effect.
Area of Science:
- Dermatology
- Neurology
- Pharmacology
Background:
- Peripheral neuropathy is a known side effect of systemic 5-fluorouracil and capecitabine.
- Topical 5-fluorouracil (Efudex) is primarily associated with dermatological adverse effects.
Observation:
- A 70-year-old male experienced worsening sensory peripheral neuropathy, including pain and paresthesias, after a 21-day course of topical 5-fluorouracil for actinic keratosis.
- Extensive work-up, including dihydropyrimidine dehydrogenase (DPD) activity tests, did not reveal an alternative cause for the neuropathy.
- Symptoms resolved upon discontinuation of topical 5-fluorouracil and did not recur with topical imiquimod treatment.
Findings:
- This case represents the first reported instance of peripheral neuropathy exacerbation linked to topical 5-fluorouracil.
- The patient's normal DPD activity suggests that 5-fluorouracil-induced neuropathy can occur even without DPD deficiency.
- The temporal relationship between drug application, symptom exacerbation, and symptom resolution strongly implicates topical 5-fluorouracil.
Implications:
- Topical 5-fluorouracil should be considered a potential cause of peripheral neuropathy, even in patients with normal DPD activity.
- Clinicians should be vigilant for neurological side effects of topical 5-fluorouracil, particularly in patients with pre-existing neuropathy.
- Further investigation into the mechanisms of topical 5-fluorouracil-induced neuropathy is warranted.
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