title: A Randomized Phase 2 Trial of Prophylactic Manuka Honey for the Reduction of Chemoradiation Therapy-Induced Esophagitis During the Treatment of Lung Cancer: Results of NRG Oncology RTOG 1012.
abstract: Randomized trials have shown that honey is effective for the prevention of radiation-induced mucositis in head and neck cancer patients. Because there is no efficacious preventative for radiation esophagitis in lung cancer patients, this trial compared liquid honey, honey lozenges, and standard supportive care for radiation esophagitis.
  
  
  
  The patients were stratified by percentage of esophagus receiving specific radiation dose (V60 Gy esophagus <30% or ≥30%) and were then randomized between supportive care, 10 mL of liquid manuka honey 4 times a day, and 2 lozenges (10 mL of dehydrated manuka honey) 4 times a day during concurrent chemotherapy and radiation therapy. The primary endpoint was patient-reported pain on swallowing, with the use of an 11-point (0-10) scale at 4 weeks (Numerical Rating Pain Scale, NRPS). The study was designed to detect a 15% relative reduction of change in NRPS score. The secondary endpoints were trend of pain over time, opioid use, clinically graded and patient-reported adverse events, weight loss, dysphagia, nutritional status, and quality of life.
  
  
  
  53 patients were randomized to supportive care, 54 were randomized to liquid honey, and 56 were randomized to lozenge honey. There was no significant difference in the primary endpoint of change in the NRPS at 4 weeks between arms. There were no differences in any of the secondary endpoints except for opioid use at 4 weeks during treatment between the supportive care and liquid honey arms, which was found to be significant (P=.03), with more patients on the supportive care arm taking opioids.
  
  
  
  Honey as prescribed within this protocol was not superior to best supportive care in preventing radiation esophagitis. Further testing of other types of honey and research into the mechanisms of action are needed.
authors.affiliation: University of California San Francisco, San Francisco, California. Electronic address: Shannon.Fogh@ucsf.edu.
authors.forename: Shannon E
authors.initials: SE
authors.lastname: Fogh
authors.affiliation: NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania.
authors.forename: Snehal
authors.initials: S
authors.lastname: Deshmukh
authors.affiliation: University of South Florida, Tampa, Florida.
authors.forename: Lawrence B
authors.initials: LB
authors.lastname: Berk
authors.affiliation: Mayo Clinic in Arizona, Scottsdale, Arizona.
authors.forename: Amylou C
authors.initials: AC
authors.lastname: Dueck
authors.affiliation: Southeast Cancer Control Consortium, Inc, CCOP, Winston-Salem, North Carolina.
authors.forename: Kevin
authors.initials: K
authors.lastname: Roof
authors.affiliation: York Cancer Center, York, Pennsylvania.
authors.forename: Sherif
authors.initials: S
authors.lastname: Yacoub
authors.affiliation: Geisinger Medical Center CCOP, Danville, Pennsylvania.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gergel
authors.affiliation: Cleveland Clinic Foundation, Cleveland, Ohio.
authors.forename: Kevin
authors.initials: K
authors.lastname: Stephans
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Andreas
authors.initials: A
authors.lastname: Rimner
authors.affiliation: Main Line CCOP, Wynnewood, Pennsylvania.
authors.forename: Albert
authors.initials: A
authors.lastname: DeNittis
authors.affiliation: Lewis Cancer & Research Pavilion at St. Joseph's/Candler, Savannah, Georgia.
authors.forename: John
authors.initials: J
authors.lastname: Pablo
authors.affiliation: UF Health Cancer Center - Orlando Health, Orlando, Florida.
authors.forename: Justin
authors.initials: J
authors.lastname: Rineer
authors.affiliation: Ohio State University Medical Center, Columbus, Ohio.
authors.forename: Terence M
authors.initials: TM
authors.lastname: Williams
authors.affiliation: Emory University, Atlanta, Georgia.
authors.forename: Deborah
authors.initials: D
authors.lastname: Bruner
mesh_terms: D000368:Aged; D059248:Chemoradiotherapy / Q000009:adverse effects*; D004035:Diet Therapy / Q000379:methods*; D004941:Esophagitis / Q000209:etiology / Q000517:prevention & control*; D005260:Female; D006722:Honey; D006801:Humans; D031649:Leptospermum; D008175:Lung Neoplasms / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D011832:Radiation Injuries / Q000209:etiology / Q000517:prevention & control*; D016896:Treatment Outcome