title: Protection of salivary function by concomitant pilocarpine during radiotherapy: a double-blind, randomized, placebo-controlled study.
abstract: OBJECTIVE
  To investigate the effect of concomitant administration of pilocarpine during radiotherapy for head-and-neck squamous cell carcinoma (HNSCC) on postradiotherapy xerostomia.
  
  
  METHODS
  A prospective, double blind, placebo-controlled randomized trial including 170 patients with HNSCC was executed to study the protective effect of pilocarpine on radiotherapy-induced parotid gland dysfunction. The primary objective endpoint was parotid flow rate complication probability (PFCP) scored 6 weeks, 6 months, and 12 months after radiotherapy. Secondary endpoints included Late Effects of Normal Tissue/Somatic Objective Management Analytic scale (LENT SOMA) and patient-rated xerostomia scores. For all parotid glands, dose-volume histograms were assessed because the dose distribution in the parotid glands is considered the most important prognostic factor with regard to radiation-induced salivary dysfunction.
  
  
  RESULTS
  Although no significant differences in PFCP were found for the two treatments arms, a significant (p = 0.03) reduced loss of parotid flow 1 year after radiotherapy was observed in those patients who received pilocarpine and a mean parotid dose above 40 Gy. The LENT SOMA and patient-rated xerostomia scores showed similar trends toward less dryness-related complaints for the pilocarpine group.
  
  
  CONCLUSIONS
  Concomitant administration of pilocarpine during radiotherapy did not improve the PFCP or LENT SOMA and patient-rated xerostomia scores. In a subgroup of patients with a mean dose above 40 Gy, pilocarpine administration resulted in sparing of parotid gland function. Therefore, pilocarpine could be provided to patients in whom sufficient sparing of the parotid is not achievable.
authors.affiliation: Department of Radiation Oncology, University Medical Center Groningen, Groningen, The Netherlands. f.r.burlage@rt.umcg.nl
authors.forename: Fred R
authors.initials: FR
authors.lastname: Burlage
authors.forename: Judith M
authors.initials: JM
authors.lastname: Roesink
authors.forename: Harm H
authors.initials: HH
authors.lastname: Kampinga
authors.forename: Rob P
authors.initials: RP
authors.lastname: Coppes
authors.forename: Chris
authors.initials: C
authors.lastname: Terhaard
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Langendijk
authors.forename: Peter
authors.initials: P
authors.lastname: van Luijk
authors.forename: Monique A
authors.initials: MA
authors.lastname: Stokman
authors.forename: Arjan
authors.initials: A
authors.lastname: Vissink
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000532:radiotherapy*; D004311:Double-Blind Method; D005260:Female; D006258:Head and Neck Neoplasms / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018721:Muscarinic Agonists / Q000008:administration & dosage* / Q000009:adverse effects; D016017:Odds Ratio; D010306:Parotid Gland / Q000187:drug effects / Q000528:radiation effects*; D010862:Pilocarpine / Q000008:administration & dosage* / Q000009:adverse effects; D011446:Prospective Studies; D011832:Radiation Injuries / Q000517:prevention & control; D011879:Radiotherapy Dosage; D012044:Regression Analysis; D013546:Sweating; D014987:Xerostomia / Q000209:etiology / Q000517:prevention & control*
chemical_list: D018721:Muscarinic Agonists; D010862:Pilocarpine