title: Radiotherapy-induced xerostomia, pre-clinical promise of LMS-611.
abstract: OBJECTIVE
  Radiotherapy-induced xerostomia (RIX) is the most common permanent side effect of radiotherapy (RT) to the head and neck (H&N). There is no effective topical treatment. LMS-611 is a mimetic of a natural lamellar body which prevents thick secretions like saliva from congesting organs. The primary objective of this study was to assess saliva properties before and during RT to the H&N. The secondary objectives were to re-assess saliva properties with the addition of LMS-611, measure inter-patient variability, correlate patient-reported symptoms with laboratory measurements and design subsequent first-in-human clinical trial of LMS-611.
  
  
  METHODS
  Patients with H&N cancer receiving RT as primary treatment were recruited. Patients completed the Groningen RIX (GRIX) questionnaire and provided saliva samples at baseline and weeks 2, 4 and 6 of RT. Saliva adhesiveness and viscosity were tested by measuring time taken to travel 5 cm down an inclined plane.
  
  
  RESULTS
  Thirty patients were enrolled. The inclined plane test (IPT) results (s) were as follows: baseline 31.3, week 2 49.7, week 4 51.1 and week 6 55.7. Wide inter-patient variability was seen at baseline. GRIX scores increased as RT progressed. Spearman rank correlation coefficient of inclined plane tests with GRIX scores was -0.06 at baseline, 0.25 at week 2, 0.12 at week 4 and 0.08 at week 6. LMS-611 concentrations of 10 and 20 mg/ml significantly reduced IPT times on saliva samples.
  
  
  CONCLUSIONS
  Saliva becomes more visco-adhesive and RIX worsens as RT progresses. There is little correlation between objective and subjective measures of RIX. The addition of LMS-611 to thick, sticky saliva restores its fluidity ex vivo. This warrants in vivo analysis of the effect of LMS-611 upon RIX.
authors.affiliation: Beatson West of Scotland Cancer Centre, 1053 Great Western Road, Glasgow, G12 0YN, UK. claire.paterson2@ggc.scot.nhs.uk.
authors.forename: Claire
authors.initials: C
authors.lastname: Paterson
authors.affiliation: Beatson West of Scotland Cancer Centre, 1053 Great Western Road, Glasgow, G12 0YN, UK.
authors.forename: B
authors.initials: B
authors.lastname: Caldwell
authors.affiliation: Lamellar Biomedical Limited, Caledonian House, Phoenix Crescent, Bellshill, ML4 3NJ, UK.
authors.forename: S
authors.initials: S
authors.lastname: Porteous
authors.affiliation: Lamellar Biomedical Limited, Caledonian House, Phoenix Crescent, Bellshill, ML4 3NJ, UK.
authors.forename: A
authors.initials: A
authors.lastname: McLean
authors.affiliation: Robertson Centre for Biostatistics, University of Glasgow, Boyd Orr Building, University Avenue, Glasgow, G12 8QQ, UK.
authors.forename: C M
authors.initials: CM
authors.lastname: Messow
authors.affiliation: Beatson West of Scotland Cancer Centre, 1053 Great Western Road, Glasgow, G12 0YN, UK.
authors.forename: M
authors.initials: M
authors.lastname: Thomson
mesh_terms: D000328:Adult; D000368:Aged; D040761:Biomimetic Materials / Q000737:chemistry / Q000627:therapeutic use*; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*; D006801:Humans; D008055:Lipids / Q000737:chemistry / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011832:Radiation Injuries / Q000188:drug therapy* / Q000209:etiology; D012463:Saliva / Q000187:drug effects* / Q000528:radiation effects*; D012636:Secretory Rate / Q000187:drug effects / Q000528:radiation effects; D014987:Xerostomia / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology
chemical_list: D008055:Lipids
keywords: GRIX; LMS-611; RIX; Radiation-induced xerostomia; Visco-ease