2711 - Stop LCNP: High Dose Steroid Therapy for Late Radiation-Associated Lower Cranial Neuropathy: An Interim Report of a Phase I Dose Finding Trial and Data Registry
Presenter(s)
Z. Belal1, C. B. Peterson2, K. Woodman3, C. E. Barbon4, H. McMillan4, S. Buoy4, J. A. Garcia4, C. D. Fuller5, S. Y. Lai5, and K. A. Hutcheson4; 1Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, 2Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, 3Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, 4Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, 5Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
Purpose/Objective(s): Long-term survivors of head and neck (H&N) radiotherapy are increasingly suffering from late-onset lower cranial neuropathy (LCNP), leading to significant disability. Case reports suggest high-dose steroid therapy may improve functional reinnervation and swallowing function in treatment-related LCNP. However, no clinical trials have assessed its tolerability, optimal dosing, or functional impact in this population. This study reports safety/tolerability and symptom response to high-dose steroid therapy in LCNP using two dosing levels.
Materials/Methods: This prospective, single-institution phase I/II trial included adult, disease-free oropharyngeal cancer survivors =2 years post-radiotherapy with late radiation-associated LCNP involving CN XII with or without CN X palsy. 9 patients received 1 mg/kg (3 in Dose 1 and 6 in Registry) and 5 patients received 3 mg/kg (Dose 2) of oral prednisone (or via gastrostomy) for five days, followed by approximately two-week taper. Registry patients were prospectively followed after a standard regimen but did not meet criteria for trial due to H&N location or prior history of surgery along CN XII.
The primary endpoint was the MDASI-HN top 5 mean score (comprising the 5 most severe symptoms in LCNP among 22 assessed items: difficulty swallowing/chewing, dry mouth, mucus, voice/speech, and choking) assessed at baseline, 1-2 weeks post-taper, and 6–10 weeks post-taper. Symptom changes were classified as improved (=0.5 SD decrease), stable (<0.5 SD change), or worsened (=0.5 SD increase). Adverse events were recorded per CTCAE v5.0. Treatment was tolerable if =2 patients per dose cohort (n=5 planned each) discontinued steroids or experienced Grade =3 toxicity. If = 3 (of n=5 per dose) subjects improve in phase I, phase II enrollment will begin at the given dose level.Results: Both dose levels were well tolerated, with no treatment discontinuations. One patient experienced Grade 3 hypertension during taper, but hypertension predated steroid therapy, and no further cases occurred post-taper.
From baseline to post-taper, median (interquartile range) changes in MDASI-HN top 5 mean scores were –0.2 (1.2) in Dose 1, –1.6 (3.6) in Dose 2, and –0.2 (2.85) in the Registry. 0/3 patients improved in Dose 1, while 3/5 improved in Dose 2 and 2/6 in the Registry. At 6-10 weeks post-taper, median changes from baseline were –0.8 (2) in Dose 1, 0 (1.85) in Dose 2, and –1.5 (4.34) in the Registry. 0/5 Dose 2 patients, 1/3 patients in Dose 1, and 3/6 met improvement criteria.Conclusion: High-dose steroid therapy was well tolerated with minimal Grade 3 toxicity. Oral/per-gastrostomy prednisone at 3mg/kg dosing met criteria to move to phase II testing for the indication of symptomatic radiation associated CN XII neuropathy. Clinical Trial Number: NCT04151082