Can Sunitinib (sunitinib malate) cause polyneuropathy?

Sunitinib and Polyneuropathy: Risk Assessment

Yes, sunitinib can cause polyneuropathy, though it is not among its most common adverse effects. While the primary evidence does not explicitly list polyneuropathy among the frequently reported adverse events, there are documented cases of neurotoxicity associated with sunitinib therapy.

Neurological Side Effects of Sunitinib

Sunitinib is a multi-targeted tyrosine kinase inhibitor that primarily works by inhibiting vascular endothelial growth factor receptors (VEGFR), platelet-derived growth factor receptors (PDGFR), and other receptor tyrosine kinases 1. While the drug is generally well-tolerated, it can cause various adverse effects, including some that affect the nervous system.

The evidence indicates several neurological concerns:

• Acute neurotoxicity has been reported with sunitinib use, potentially related to increased VEGF levels resulting from receptor inhibition 2
• Severe neurological symptoms have been documented in patients receiving sunitinib for renal cell carcinoma 3
• Some cases have presented with symptoms resembling reversible posterior leukoencephalopathy syndrome 3

Common vs. Rare Adverse Effects

The most commonly reported adverse effects of sunitinib include:

• Fatigue and asthenia
• Gastrointestinal disturbances (diarrhea, nausea)
• Dermatological effects (hand-foot syndrome, skin discoloration)
• Hypertension
• Hematologic toxicities (neutropenia, thrombocytopenia)
• Hypothyroidism
• Cardiotoxicity 1, 4

While polyneuropathy is not specifically listed among the common adverse effects in the guidelines, case reports suggest that neurological complications can occur, though they appear to be less frequent than other toxicities.

Management Recommendations for Patients on Sunitinib

For patients on sunitinib therapy, the following monitoring approach is recommended:

1. Baseline neurological assessment before initiating therapy
2. Regular monitoring for neurological symptoms during treatment
3. Prompt evaluation of any new neurological symptoms including:
   • Numbness or tingling in extremities
   • Motor weakness
   • Gait disturbances
   • Sensory changes

If polyneuropathy or other neurological symptoms develop:

• Consider dose interruption or reduction
• Evaluate for other potential causes of neuropathy
• Provide appropriate supportive care
• In severe cases, discontinuation may be necessary 1, 4

Risk Factors and Special Considerations

Patients with the following may be at higher risk for developing neurological complications:

• Pre-existing neuropathy
• Diabetes mellitus
• History of neurotoxic medication exposure
• Advanced age
• Renal dysfunction 5

Clinical Implications

The potential for sunitinib to cause polyneuropathy should be considered when:

1. Evaluating unexplained neurological symptoms in patients receiving the drug
2. Making treatment decisions for patients with pre-existing neuropathy
3. Counseling patients about possible adverse effects before initiating therapy

While sunitinib offers significant benefits in treating conditions like gastrointestinal stromal tumors (GIST) and renal cell carcinoma, clinicians should remain vigilant about potential neurological complications to optimize patient outcomes and quality of life.