STOP Lower Cranial Neuropathy: High-Dose Corticosteroid Therapy for Late Radiation-Associated Lower Cranial Neuropathy in Oropharyngeal Cancer Survivors: Interim Analysis of a Phase I Dose-Finding Trial.

PURPOSE: Radiation-associated lower cranial neuropathy (LCNP) is a debilitating late complication among head and neck cancer (HNC) survivors, leading to progressive dysphagia, aspiration, and loss of nutritional independence. No proven therapies exist for LCNP. This phase I/II dose-finding trial (STOP LCNP, NCT04151082) and parallel registry study prospectively evaluated the safety, feasibility, tolerability, and symptomatic response of high-dose corticosteroid therapy for radiation-associated LCNP.

METHODS AND MATERIALS: Interim phase I dose-finding report from the STOP LCNP trial. Eligible participants were disease-free oropharyngeal cancer survivors ≥2 years after radiation therapy with electromyography-confirmed LCNP (CN XII ± X) absent structural/malignant etiology. Phase I testing included oral prednisone 1 mg/kg (dose 1, n = 3) or 3 mg/kg (dose 2, n = 5) daily for 5 days (2-week taper). A parallel registry (n = 6) enrolled broader HNC survivors treated with 1 mg/kg. Rule-based phase I dose-escalation decisions were prespecified for tolerability and symptom response (primary endpoint); ≥1.315-unit decrease in MD Anderson Symptom Inventory-Head and Neck Module Top 5 mean symptom score from baseline to 1 to 2 weeks posttaper indicated clinically meaningful improvement. Secondary endpoints included clinician-graded measures of bulbar function, electromyography, and patient-reported outcome measures.

RESULTS

All regimens were feasible and well tolerated. Insomnia (n = 5, grade 1) was the most frequent adverse event with no treatment discontinuations. At 1 to 2 weeks posttaper, the median MD Anderson Symptom Inventory-Head and Neck Module Top 5 change was -0.2 in 1 mg/kg and -1.6 in 3 mg/kg; 3 of 5 patients receiving 3 mg/kg achieved clinically meaningful improvement not maintained at 6 to 10 weeks. No consistent improvements were observed in objective functional or electrophysiologic measures at either dose level.

CONCLUSIONS

High-dose corticosteroid therapy was feasible and tolerable in long-term HNC survivors with LCNP. Short-term symptomatic improvement was achieved in the majority treated with 3 mg/kg but was not reflected in clinician-graded measures of bulbar function and not durable by 6 to 10 weeks at either dosing.