Radiation-induced xerostomia (dry mouth) is not just a localized side effect of radiation treatment for head and neck cancer. It can cause a painful condition that affects the entire body, beginning with the patient’s inability to swallow and leading to a cascade of malnutrition and poor health. The current standard of treatment for this syndrome utilizes pilocarpine and similar medications taken orally. Although pilocarpine does improve the xerostomia, it causes unpleasant side effects such as polyuria, hyperhydrosis, dizziness, and diarrhea.
Non-pharmaceutical alternative treatment
The American Society for Radiation Oncology (ASTRO) reported encouraging results from the trial of an alternative treatment to pilocarpine in the International Journal of Radiation Oncology • Biology • Physics (Red Journal). The randomized trial, RTOG 0537, is a phase 3, multicenter trial comparing acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) with pilocarpine.1 The study‘s lead author, Raimond K. W. Wong, MBBS, a radiation oncologist and associate professor in the department of oncology at McMaster University in Hamilton, ON, Canada, reported that ALTENS is equally as effective as the current standard treatment.
The group decided to pursue ALTENS as an alternative treatment for radiation-induced xerostomia after a nonrandomized trial published in 2003 found that ALTENS achieved positive results as a therapeutic modality for the condition.2 Similar to a TENS unit, ALTENS utilizes electrodes that the clinician places on the patient’s skin at pre-assigned acupuncture points. The electrodes stimulate these points with low frequency and high intensity pulses. Results demonstrated that patients who received ALTENS had a positive response, and that the treatment could be undertaken in a multicenter trial.3
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In the phase 3 trial, the investigators recruited 148 patients from 13 cancer centers in the United States and Canada from August 2010 to December 2011. In order to be eligible, subjects had to complete radiation therapy (with or without chemotherapy) within 2 years prior to enrolling in the trial. They had to have xerostomia of grade 1 or higher based on the Common Terminology Criteria for Adverse Events 3.0.1 Subjects also had to qualify with a Zubrod health performance status of zero to two, of a scale of zero to four. On the Zubrod score, zero indicates that a patient is “fully active, able to carry on all predisease activities without restriction” while a score of four indicates that the patient is “completely disabled, cannot perform any self-care, and is totally confined to bed or chair.”1 Two of the 148 patients originally recruited were disqualified, leaving 146 patients in the trial. Of these, one group of 73 was randomly assigned to receive ALTENS, and the other 73 received pilocarpine.
ALTENS arm
Treatment began within 14 days of enrollment. Patients in the ALTENS group received two, 20-minute ALTENS sessions weekly for 12 weeks, for a total of 24 ALTENS sessions. Each patient could take a total of two weeks off; missed treatments were made up during the 23-week treatment period. No patient received more than three ALTENS sessions in a week. In this group 68 patients (93%) completed more than 85% of the treatments.1
Pilocarpine arm
Patients in the pilocarpine group also began treatment within 14 days of enrollment. They were given 5 mg of pilocarpine orally three times a day for 12 weeks. If they missed a dose of medication it was not made up. In this group 53 patients (73%) completed more than 85% of the treatments.1
Fewer adverse effects with ALTENS
There was no significant difference between the three highest grade adverse treatment-related events (headache, dry mouth, and blurred vision) between the two groups. Only 15 patients in the ALTENS arm reported adverse events of grade 3 or less. By contrast, 45 patients in the pilocarpine arm reported comparable adverse events.1
Symptom improvement
For both arms of the trial, the patients’ xerostomia symptoms were assessed before treatment and at 4, 6, 9, and 15 months thereafter. The patients completed self-evaluations utilizing the University of Michigan’s Xerostomia-Related Quality of Life Scale (XeQOLS). This scale contains 15 items that measure four areas: physical functioning, pain/discomfort, personal/psychologic functioning, and social functioning. The investigators averaged all of the responses on a scale of zero to four where the higher the score, the more severe the xerostomia. Of the 96 subjects who were eligible for study analysis, those in the ALTENS arm demonstrated a slightly better quality of life than the patients in the pilocarpine group. According to the researchers: “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… Some patients in the ALTENS group demonstrated lasting response and indicated the possibility to induce salivary gland tissue regeneration.”1
The Canadian group calls for randomized, controlled placebo trials to confirm that ALTENS is as effective for the treatment of radiation-induced dry mouth as their work has demonstrated.
Bette Weinstein Kaplan is a medical writer based in Tenafly, New Jersey.
References
1. Wong RK, Deshmukh S, Wyatt G, et al. Acupuncture-like transcutaneous electrical nerve stimulation versus pilocarpine in treating radiation-induced xerostomia: results of RTOG 0537 phase 3 study. Int J Radiat Oncol Biol Phys. 2015;92(2):220-227.
2. Wong RK, Jones GW, Sagar SM, et al. A Phase I-II study in the use of acupuncture-like transcutaneous nerve stimulation in the treatment of radiation-induced xerostomia in head-and-neck cancer patients treated with radical radiotherapy. Int J Radiat Oncol Biol Phys. 2003; 57: 472-480.
3. Wong RK, James JL, Sagar S, et al. Phase 2 results from radiation therapy oncology group study 0537: A phase 2/3 study comparing acupuncture-like transcutaneous electrical nerve stimulation versus pilocarpine in treating early radiation-induced xerostomia. Cancer. 2012; 118: 4244-4252.
