Peripheral neuropathy associated with capecitabine.

Area of Science:

• Oncology
• Clinical Pharmacology
• Neuro-oncology

Background:

• 5-fluorouracil (5-FU) is associated with rare peripheral neuropathy.
• Capecitabine (CAP), an oral prodrug of 5-FU, has not previously been reported to cause peripheral neuropathy.
• Pancreatic cancer patients receiving CAP with concurrent radiation therapy (XRT) were evaluated for potential neurotoxicity.

Observation:

• Two patients out of 28 developed symptoms consistent with peripheral neuropathy during CAP treatment for pancreatic cancer.
• Patient A experienced foot drop during CAP-XRT, while Patient B reported paresthesias during CAP monotherapy.
• Neurologic examinations, imaging, and DPD activity assays were performed; EMG/nerve conduction studies confirmed sensorimotor peripheral neuropathy in both patients.

Findings:

• Both patients exhibited sensorimotor peripheral neuropathy despite normal dihydropyrimidine dehydrogenase (DPD) activity.
• Neurologic symptoms resolved in both patients after CAP dose modification or temporary cessation.
• The exact etiology remains unclear, but 5-FU or its metabolites are suspected contributors to CAP-induced neurotoxicity.

Implications:

• This study highlights the potential for capecitabine-associated peripheral neuropathy, previously unreported.
• Clinicians should be aware of this potential adverse effect and monitor patients closely for neurotoxicity symptoms.
• Dose modification of capecitabine may be necessary to manage and resolve neurotoxicity, ensuring patient safety and treatment continuity.