Padcev-Induced Peripheral Neuropathy: Reversibility After Treatment Discontinuation
Padcev (enfortumab vedotin)-induced peripheral neuropathy can improve or resolve after stopping treatment, though complete reversibility is not guaranteed and symptoms may initially worsen before improving.
Evidence for Reversibility
The reversibility of enfortumab vedotin-induced peripheral neuropathy follows patterns similar to other chemotherapy-induced peripheral neuropathies, with important caveats:
- Grade 1-2 peripheral neuropathy occurs in 56.4% of patients treated with enfortumab vedotin plus pembrolizumab, while grade 3 neuropathy occurs in 6.8% 1
- Peripheral neuropathy is one of the key toxicities requiring monitoring alongside skin reactions, ocular disorders, and hyperglycemia 1
- Patients with pre-existing neuropathy or grade ≥2 neuropathy are typically excluded from enfortumab vedotin treatment eligibility 1
Clinical Course After Discontinuation
Based on chemotherapy-induced peripheral neuropathy patterns and available data:
- A "coasting phenomenon" may occur where neuropathy symptoms can worsen for 2-3 months after treatment cessation before improvement begins, similar to oxaliplatin-induced neuropathy 2
- Improvement is more likely with lower-grade neuropathy (grades 1-2) compared to grade 3 or higher 3, 4
- Complete resolution is not guaranteed, particularly in patients who developed severe (grade 3+) neuropathy during treatment 1
Management Strategy During Treatment
To optimize outcomes and potentially improve reversibility:
- Baseline neurological evaluation is essential before initiating enfortumab vedotin, with monitoring before each treatment cycle 2
- Dose interruption or modification should occur promptly when peripheral neuropathy develops, rather than waiting for severe symptoms 5
- Early detection and intervention allow most patients to continue treatment while minimizing permanent nerve damage 5
Prognostic Considerations
Interestingly, the development of peripheral neuropathy may indicate treatment efficacy:
- Patients who develop enfortumab vedotin-associated peripheral neuropathy demonstrate significantly higher response rates (58.8% vs 34.9%, p=0.032) and longer progression-free survival (8.05 vs 6.31 months, p=0.017) compared to those without neuropathy 6
- Overall survival was also superior in patients who developed neuropathy (not reached vs 11.57 months, p=0.008) 6
Treatment of Established Neuropathy
If neuropathy persists after discontinuation:
- Duloxetine is the only agent with strong evidence for treating chemotherapy-induced peripheral neuropathy and should be offered as first-line treatment 1, 2
- Gabapentin or pregabalin serve as reasonable alternatives for neuropathic pain management 2
- Tricyclic antidepressants (nortriptyline or desipramine) may be considered despite limited specific evidence for chemotherapy-induced neuropathy 1
Critical Caveats
- Permanent neuropathy can occur, particularly with cumulative dosing or delayed intervention 2
- The symmetric, distal, length-dependent "glove and stocking" distribution is characteristic of drug-induced neuropathy 2
- Risk factors that worsen prognosis include pre-existing diabetes, renal insufficiency, vitamin deficiencies, and concurrent neurotoxic medications 2