Xerostomia health-related quality of life: NRG oncology RTOG 0537.

PURPOSE: The purpose of this secondary analysis was to determine change in overall health-related quality of life (HRQOL) based on patient data obtained from NRG Oncology RTOG 0537 as measured by the RTOG-modified University of Washington Head and Neck Symptom Score (RM-UWHNSS). METHODS: A multi-site prospective randomized clinical trial design stratified 137 patients with post-radiation therapy xerostomia according to prior pilocarpine (PC) treatment and time after radiation therapy and/or chemotherapy and randomized patients into two groups. Patients were assigned to acupuncture or PC. Twenty-four sessions of acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) were administered over 12 weeks, or oral PC (5 mg) three times daily over the same 12 weeks. The RM-UWHNSS was administered at baseline and at 4, 6, 9, and 15 months after the date of randomization. RESULTS: There were no between-arm differences in change scores on the RM-UWHNSS in the individual items, total score, or factor scores. For statistical modeling, race and time were significant for all outcomes (total and factor scores), while treatment arm was not significant. The ALTENS arm showed greater yet nonsignificant improvement in outcomes compared to the PC arm. CONCLUSION: Although no significant treatment differences were seen in this trial, patients receiving ALTENS consistently had lower scores, indicating better function, as compared to those receiving PC. Radiation-induced xerostomia improved over time for all patients.

Acupuncture-Like Transcutaneous Electrical Nerve Stimulation Versus Pilocarpine in Treating Radiation-Induced Xerostomia: Results of RTOG 0537 Phase 3 Study.

PURPOSE AND OBJECTIVES: This report presents the analysis of the RTOG 0537 multicenter randomized study that compared acupuncture-like transcutaneous stimulation (ALTENS) with pilocarpine (PC) for relieving radiation-induced xerostomia. METHODS AND MATERIALS: Eligible patients were randomized to twice-weekly 20-minute ALTENS sessions for 24 sessions during 12 weeks or PC (5 mg 3 times daily for 12 weeks). The primary endpoint was the change in the University of Michigan Xerostomia-Related Quality of Life Scale (XeQOLS) scores from baseline to 9 months from randomization (MFR). Secondary endpoints included basal and citric acid primed whole salivary production (WSP), ratios of positive responders (defined as patients with ≥20% reduction in overall radiation-induced xerostomia symptom burden), and the presence of adverse events based on the Common Terminology Criteria for Adverse Events version 3. An intention-to-treat analysis was conducted. RESULTS: One hundred forty-eight patients were randomized. Only 96 patients completed the required XeQOLS and were evaluable at 9 MFR (representing merely 68.6% statistical power). Seventy-six patients were evaluable at 15 MFR. The median change in the overall XeQOLS in ALTENS and PC groups at 9 and 15 MFR were -0.53 and -0.27 (P=.45) and -0.6 and -0.47 (P=.21). The corresponding percentages of positive responders were 81% and 72% (P=.34) and 83% and 63% (P=.04). Changes in WSP were not significantly different between the groups. Grade 3 or less adverse events, mostly consisting of grade 1, developed in 20.8% of patients in the ALTENS group and in 61.6% of the PC group. CONCLUSIONS: The observed effect size was smaller than hypothesized, and statistical power was limited because only 96 of the recruited 148 patients were evaluable. The primary endpoint-the change in radiation-induced xerostomia symptom burden at 9 MFR-was not significantly different between the ALTENS and PC groups. There was significantly less toxicity in patients receiving ALTENS.

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.

BACKGROUND: In this phase 2 component of a multi-institutional, phase 2/3, randomized trial, the authors assessed the feasibility and preliminary efficacy of acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) in reducing radiation-induced xerostomia. METHODS: Patients with cancer of the head and neck who were 3 to 24 months from completing radiotherapy with or without chemotherapy (RT ± C) and who were experiencing xerostomia symptoms with basal whole saliva production ≥0.1 mL per minute and were without recurrence were eligible. Patients received twice weekly ALTENS sessions (24 sessions over 12 weeks) using a proprietary electrical stimulation unit. The primary study objective was to assess the feasibility of ALTENS treatment. Patients were considered compliant if 19 of 24 ALTENS sessions were delivered, and the targeted compliance rate was 85%. Secondary objectives measured treatment-related toxicities and the effect of ALTENS 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. The median age was 60 years, 84% of patients were men, 70% completed RT ± C for >12 months, and 21% had previously received pilocarpine. Thirty-four patients completed all 24 ALTENS sessions, 9 patients completed 20 to 23 sessions, and 1 patient completed 19 sessions, representing a 94% total compliance rate. Six-month XeQOLS scores were available for 35 patients and indicated that 30 patients (86%) achieved a positive treatment response with a mean ± standard deviation reduction of 35.9% ± 36.1%. Five patients developed grade 1 or 2 gastrointestinal toxicity, and 1 had a grade 1 pain event. CONCLUSIONS: The current results indicated that ALTENS treatment for radiation-induced xerostomia can be delivered uniformly in a cooperative, multicenter setting and produces possible beneficial treatment response. Given these results, the phase 3 component of this study was initiated.

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.

PURPOSE: Recent studies have suggested that acupuncture may improve radiation-induced xerostomia with an increase in the median salivary flow rate and sustained symptom relief. An acupuncture-like transcutaneous nerve stimulation method (Codetron) without invasive needles was developed to mimic acupuncture treatment. This Phase I-II study examined the effectiveness of Codetron in treating radiation-induced xerostomia. METHODS AND MATERIALS: Patients with symptomatic xerostomia after radical radiotherapy for head-and-neck cancer but with evidence of residual salivary function were recruited into the study. Two 6-week courses of Codetron treatment of acupuncture points preselected according to traditional Chinese medicine principles were given with a 2-week break between each course. Basal and citric acid-primed whole saliva production were measured at baseline and up to 1 year after treatment completion. Xerostomia symptoms were assessed by a five-item xerostomia symptom questionnaire with a visual analog scale and quality of life was evaluated using the Head and Neck Radiotherapy Questionnaire. RESULTS: We enrolled 46 patients in the study. All patients had received radiotherapy doses of >or=50 Gy to bilateral head-and-neck fields, including the parotid glands. Of the 46 patients, 37 completed the follow-up assessments at 3 and 6 months after treatment completion. No Codetron treatment-related complications occurred. Improvement in xerostomia symptoms was noted, with a mean increase in the visual analog scale score of 86 (p < 0.0005) and 77 (p < 0.0001) at 3 and 6 months after treatment completion, respectively. For all patients, the increase in the mean basal and citric acid-primed whole saliva production at 3 and 6 months after treatment completion was also statistically significant (p < 0.001 and p < 0.0001, respectively). No statistically significant change in the quality-of-life evaluation compared with baseline was observed. CONCLUSION: The results suggest that Codetron treatment improves whole saliva production and related symptoms in patients with radiation-induced xerostomia. The treatment effects were sustained for at least 6 months after Codetron treatment completion. A prospective randomized Phase III trial with appropriate controls is being planned.