Phase 2 results from Radiation Therapy Oncology Group Study 0537

Abstract

Purpose This phase II component of a multi-institutional phase II/III randomized trial assessed the feasibility and preliminary efficacy of acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) in reducing radiation-induced xerostomia. Methods Head and neck cancer patients who were 3–24 months from completing radiotherapy ± chemotherapy (RT±C) and experiencing xerostomia symptoms with basal whole saliva production ≥0.1 ml/min and without recurrence were eligible. Patients received twice weekly ALTENS sessions (24 over 12 weeks) using a Codetron™ unit. The primary objective assessed the feasibility of ALTENS treatment. A patient was considered compliant if 19/24 ALTENS were delivered, with a targeted 85% compliance rate. Secondary objectives measured treatment-related toxicities and ALTENS effect on overall radiation-induced xerostomia burden using the University of Michigan Xerostomia-Related Quality of Life Scale (XeQOLS). Results Of 48 accrued patients, 47 were evaluable. Median age was 60 years; 84% were male, 70% completed RT±C for > 12 months and 21% had received prior pilocarpine. All ALTENS sessions were completed in 34 patients, but 9 and 1 completed 20–23 and 19 sessions respectively, representing a 94% total compliance rate. 6-month XeQOLS scores were available for 35 patients; 30 (86%) achieved a positive treatment response with a mean reduction of 35.9% (SD 36.1). Five patients developed grade 1–2 gastrointestinal toxicity and one had grade 1 pain event. Conclusions ALTENS treatment for radiation-induced xerostomia can be uniformly delivered in a cooperative multicenter setting and has possible beneficial treatment response. Given these results, the phase III component of this study was initiated.

Submandibular Gland Transfer for the Prevention of Postradiation Xerostomia in Patients with Head and Neck Cancer: A Systematic Review and Meta-Analysis

“…To date, many therapeutic agents including saliva substitutes [26], intensity-modulated radiotherapy [27,28], pilocarpine [29,30,31,32], acupuncture [33,34], and amifostine [35,36] had been available to alleviate radiation-induced xerostomia, but they rarely had curable effects or were even controversial regarding the safety of their use. So, the best method to treat postradiation xerostomia would be to choose preventive measures.…”

Accupuncture-like transcutaneous electrical nerve stimulation therapy success using a commercially available unit 8 years post-radiation for xerostomia: a case report

“…The multi-institutional, 48 patient, phase II trial that followed showed similar efficacy with a positive treatment response in 86% of patients using the self-reported XeQOLS surveys to evaluate response at baseline and 6 months post-treatment. 5 Eligibility for ALTENS was limited to those within 24 months of completing chemoradiation. 5 In a 148 patient, phase III multi-institutional randomised study comparing ALTENS with pilocarpine therapy, Wong et al 6 found ALTENS ALTENS therapy success using a commercially available unit 8 years post-radiation for xerostomia ALTENS therapy success using a commercially available unit 8 years post-radiation for xerostomia was just as efficacious as pilocarpine but produced significantly less grade 3 or less adverse events (20·8-61·6%).…”

“…5 Eligibility for ALTENS was limited to those within 24 months of completing chemoradiation. 5 In a 148 patient, phase III multi-institutional randomised study comparing ALTENS with pilocarpine therapy, Wong et al 6 found ALTENS ALTENS therapy success using a commercially available unit 8 years post-radiation for xerostomia ALTENS therapy success using a commercially available unit 8 years post-radiation for xerostomia was just as efficacious as pilocarpine but produced significantly less grade 3 or less adverse events (20·8-61·6%). A secondary analysis of this study using the RTOG-modified University of Washington Head and Neck Symptom Score to assess overall health-related quality of life demonstrated consistently lower scores, indicating better function, for patients randomised to the ALTENS arm compared with those randomised to pilocarpine.…”

“…2,3 Acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) treatment has emerged as a promising new modality to improve saliva production and related symptoms without the associated cholinergic side effects caused by sympathomimetic agents. [4][5][6][7] Reports generated from single and multi-institutional studies have demonstrated benefit in patients initiating ALTENS therapy within 3-27 months of completing chemoradiation. [4][5][6][7] In addition, a previous case report found ALTENS therapy to be effective in a patient 5 years removed from completion of chemoradiation.…”

“…[4][5][6][7] Reports generated from single and multi-institutional studies have demonstrated benefit in patients initiating ALTENS therapy within 3-27 months of completing chemoradiation. [4][5][6][7] In addition, a previous case report found ALTENS therapy to be effective in a patient 5 years removed from completion of chemoradiation. 8 Unfortunately, the TENS unit produced by Codetron (Buffalo, NY, USA) used to conduct these studies is no longer manufactured.…”