Latest RTOG 0537 Data Indicate Electrical Nerve Stimulation May Provide Relief for Radiation-Induced Dry Mouth
Phase III results of Radiation Therapy Oncology Group (RTOG) 0537 indicate that acupuncture-like, transcutaneous electrical nerve stimulation (ALTENS) may be equally effective as the prescription medication pilocarpine, the current standard of care, to treat radiation-induced xerostomia (dry mouth), according to a study published by Wong et al in the International Journal of Radiation Oncology • Biology • Physics.
RTOG 0537 is a phase II/III, multicenter, randomized trial comparing ALTENS with pilocarpine, which is the current standard of treatment for radiation-induced xerostomia.
Study Background
RTOG 0537 was designed based on evidence published in 2003 from a nonrandomized, phase II trial that ALTENS was a potential alternative treatment for radiation-induced xerostomia. ALTENS treats symptoms through electrodes placed on the skin at the locations of preselected acupuncture points. The electrodes deliver low-frequency, high-intensity pulses to stimulate acupuncture points. Phase II results of RTOG 0537, published in 2012, proved a positive response in patients who received ALTENS for radiation-induced xerostomia and demonstrated it was feasible to deliver ALTENS treatment in a multicenter trial.
The phase III stage of the study accrued 148 patients from August 2010 to December 2011 at 13 cancer centers in the United States and Canada. Eligible patients had completed radiation therapy with or without chemotherapy 3 months to 2 years prior to enrolling in the study with no evidence of recurrence; reported grade 1 or higher xerostomia based on the Common Terminology Criteria for Adverse Events version 3.0; and a Zubrod performance status of 0 to 2.
Of the 146 patients eligible for the study, 73 patients were randomly assigned to receive ALTENS, and 73 patients were randomly assigned to receive pilocarpine. All patients began treatment within 14 days of enrolling. Patients in the ALTENS arm received two 20-minute ALTENS sessions each week for 12 weeks (total of 24 ALTENS sessions). Patients were allowed 2 weeks of no treatment, and any missed sessions were rescheduled during the 12-week period; patients did not exceed 3 sessions per week. Patients in the pilocarpine arm received 5 mg of pilocarpine orally three times a day for 12 weeks; missed doses were not administered at a later time. Ninety-three percent (68) of patients in the ALTENS arm completed more than 85% of treatments, compared with 73% (53) of patients in the pilocarpine arm.
Patients’ xerostomia symptoms were assessed at baseline and at 4, 6, 9, and 15 months after their randomization date using the University of Michigan’s Xerostomia-Related Quality-of-Life Scale (XeQOLS). XeQOLS is a patient-reported, 15-item scale that measures four domains: physical functioning, pain/discomfort, personal/psychologic functioning, and social functioning. Patient responses to all four domains were averaged, and the total scores ranged from 0 to 4; an increased xerostomia burden is indicated by a higher score.
Study Results
At 9 months after randomization, 96 patients from both arms had completed all items to be included in the analysis. Four patients in the ALTENS arm and 11 patients in the pilocarpine arm had withdrawn from the trial. Five patients did not complete the baseline assessment prior to treatment, and 11 patients did not complete the XeQOLS prior to treatment. Six patients in the ALTENS arm and 13 in the pilocarpine arm either did not complete the XeQOLS or completed the XeQOLS outside of the designated time period.
In the 96 patients eligible for analysis, the mean baseline XeQOLS score of the ALTENS arm was slightly lower than that in the pilocarpine arm (1.5 vs 1.7), which indicates a slightly higher quality of life for patients in the ALTENS arm. Baseline XeQOLS scores were subtracted from follow-up XeQOLS scores; a negative change would indicate improvement in xerostomia burden. At the 9-month follow-up (the study’s primary endpoint), the median change in XeQOLS score was −0.53 for patients in the ALTENS arm and −0.27 for patients in the pilocarpine arm. At follow-up 15 months from randomization, the median change in XeQOLS score was −0.60 for patients in the ALTENS arm and −0.47 for patients in the pilocarpine arm. The median change in XeQOLS scores consistently improved for patients in the ALTENS arm; however, none of the differences was statistically significant. The proportions of patients who had 20% or more improvement from their baseline XeQOLS scores were consistently higher in the ALTENS arm, and the difference was significant at 15 months from randomization.
Overall results yielded one grade 3 adverse event (headache) in the ALTENS arm and two grade 3 adverse events (dry mouth and blurred vision) in the pilocarpine arm. In the ALTENS arm, 20.9% (15) of patients reported nonhematologic adverse events of grade 3 or less. In the pilocarpine arm, 61.6% (45) of patients reported nonhematologic adverse events of grade 3 or less. At follow-up 9 months from randomization, there was no significant difference in the highest grade of adverse events related to treatment between the two arms of patients.
“Radiation-induced xerostomia is a challenging side effect to treat. It makes it difficult and sometimes painful for patients to swallow food, thereby affecting their nutrition and physical wellbeing. Oral pilocarpine and similar medications are not well tolerated by patients due to various side effects including sweating, diarrhea, frequent urination, and dizziness. Multiple previous studies using needle acupuncture supported the potential for acupuncture approaches in treating xerostomia symptoms, so RTOG 0537 was developed to specifically explore those findings,” said Raimond K .W. Wong, MBBS, the study’s lead author and radiation oncologist and Associate Professor in the Department of Oncology at McMaster University.
“These phase III results of RTOG 0537 indicate that ALTENS, a needleless acupuncture approach, could provide an alternative treatment option that has fewer side effects and, in turn, helps improve quality of life for patients with radiation-induced xerostomia. Some patients in the ALTENS group demonstrated lasting response and indicated the possibility to induce salivary gland tissue regeneration. Randomized, controlled, placebo trials are necessary to confirm ALTENS’ treatment efficacy for painful, radiation-induced dry mouth, a debilitating condition for many patients.”
Dr. Wong is the corresponding author of the International Journal of Radiation Oncology • Biology • Physics article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
