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.
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.
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.
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.
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The authors acknowledge Graham Park, Head of Technical Development, Lamellar Biomedical Limited, who contributed to the study design and saliva sample analysis but sadly passed away prior to study completion.
The following authors contributed to the study design: R Jones, J Paul and C Bray (all Cancer Research UK Clinical Trials Unit, Beatson WoSCC), and N Brittain and J Lang (NHS Greater Glasgow & Clyde Research & Development Department).
A McConnachie (Robertson Centre for Biostatistics, University of Glasgow) contributed to the statistical analysis.
Staff funding was provided by Scottish Cancer Research Network and NHS Research Scotland Career Researcher Fellowship, both from Chief Scientists Office, Scottish Government Health Directorate.
A James (Beatson WoSCC) and A J Chalmers (Institute of Cancer Sciences, University of Glasgow) provided assistance with the preparation of the manuscript.
Conflict of interest
Funding for this study was provided by Lamellar Biomedical Limited. Dr. Claire Paterson has no conflicts of interests to declare and had full access to all of the primary data. Review of the data by the journal is welcome.
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Paterson, C., Caldwell, B., Porteous, S. et al. Radiotherapy-induced xerostomia, pre-clinical promise of LMS-611. Support Care Cancer 24, 629–636 (2016). https://doi.org/10.1007/s00520-015-2823-5
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