title: Acupuncture-Like Transcutaneous Electrical Nerve Stimulation Versus Pilocarpine in Treating Radiation-Induced Xerostomia: Results of RTOG 0537 Phase 3 Study.
abstract: OBJECTIVE
  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
  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.
authors.affiliation: McMaster University, Juravinski Cancer Centre, Hamilton, Ontario, Canada. Electronic address: wongrai@hhsc.ca.
authors.forename: Raimond K W
authors.initials: RK
authors.lastname: Wong
authors.affiliation: NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania.
authors.forename: Snehal
authors.initials: S
authors.lastname: Deshmukh
authors.affiliation: Michigan State University, East Lansing, Michigan.
authors.forename: Gwen
authors.initials: G
authors.lastname: Wyatt
authors.affiliation: McMaster University, Juravinski Cancer Centre, Hamilton, Ontario, Canada.
authors.forename: Stephen
authors.initials: S
authors.lastname: Sagar
authors.affiliation: Roswell Park Cancer Institute, Buffalo, New York.
authors.forename: Anurag K
authors.initials: AK
authors.lastname: Singh
authors.affiliation: McGill University, Montreal, Quebec, Canada.
authors.forename: Khalil
authors.initials: K
authors.lastname: Sultanem
authors.affiliation: Centre Hospitalier de l'Université de Montréal-Hôpital Notre-Dame, Montreal, Quebec, Canada.
authors.forename: Phuc F
authors.initials: PF
authors.lastname: Nguyen-Tân
authors.affiliation: University of California San Francisco, San Francisco, California.
authors.forename: Sue S
authors.initials: SS
authors.lastname: Yom
authors.affiliation: Yale-New Haven Hospital Saint Raphael Campus, New Haven, Connecticut.
authors.forename: Joseph
authors.initials: J
authors.lastname: Cardinale
authors.affiliation: University Hospitals of Cleveland, Cleveland, Ohio.
authors.forename: Min
authors.initials: M
authors.lastname: Yao
authors.affiliation: McMaster University, Juravinski Cancer Centre, Hamilton, Ontario, Canada.
authors.forename: Ian
authors.initials: I
authors.lastname: Hodson
authors.affiliation: University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.
authors.forename: Chance L
authors.initials: CL
authors.lastname: Matthiesen
authors.affiliation: Cleveland Clinic Foundation, Cleveland, Ohio.
authors.forename: John
authors.initials: J
authors.lastname: Suh
authors.affiliation: John H. Stroger, Jr. Hospital of Cook County MB-CCOP, Chicago, Illinois.
authors.forename: Harish
authors.initials: H
authors.lastname: Thakrar
authors.affiliation: NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania.
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Pugh
authors.affiliation: University of South Florida H. Lee Moffitt Cancer Center, Tampa, Florida.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Berk
mesh_terms: D015670:Acupuncture Therapy; D000328:Adult; D000368:Aged; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D057194:Intention to Treat Analysis; D008297:Male; D008875:Middle Aged; D010862:Pilocarpine / Q000627:therapeutic use*; D011788:Quality of Life; D011878:Radiotherapy / Q000009:adverse effects; D012472:Salivation; D013997:Time Factors; D004561:Transcutaneous Electric Nerve Stimulation / Q000379:methods*; D014987:Xerostomia / Q000209:etiology / Q000628:therapy*
chemical_list: D010862:Pilocarpine
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