Randomized placebo-controlled phase II trial of high-dose melatonin mucoadhesive oral gel for the prevention and treatment of oral mucositis in patients with head and neck cancer undergoing radiation therapy concurrent with systemic treatment

• A. Lozano ^[8] ; J. Marruecos ^[9] ; J. Rubió ^[9] ; N. Farré ^[1] ; J. Gómez Millán ^[2] ; R. Morera ^[3] ; I. Planas ^[10] ; M. Lanzuela ^[4] ; M.G. Vázquez Masedo ^[5] ; L. Cascallar ^[6] ; J. Giralt ^[11] ; G. Escames ^[12] ; V. Valentí ^[7] ; P. Grima ^[13] ; R. Bosser ^[14] ; C. Tarragó ^[15] ; R. Mesía ^[16]
  1. [1] Hospital de la Santa Creu i Sant Pau

     Hospital de la Santa Creu i Sant Pau

     Barcelona, España

     
  2. [2] Hospital Universitario Virgen de la Victoria

     Hospital Universitario Virgen de la Victoria

     Málaga, España

     
  3. [3] Hospital Universitario La Paz

     Hospital Universitario La Paz

     Madrid, España

     
  4. [4] Hospital Miguel Servet

     Hospital Miguel Servet

     Zaragoza, España

     
  5. [5] Hospital Clínico San Carlos de Madrid

     Hospital Clínico San Carlos de Madrid

     Madrid, España

     
  6. [6] Complexo Hospitalario Universitario de Santiago

     Complexo Hospitalario Universitario de Santiago

     Santiago de Compostela, España

     
  7. [7] Hospital de Sant Pau i Santa Tecla

     Hospital de Sant Pau i Santa Tecla

     Tarragona, España

     
  8. [8] Institut Català d’Oncologia (ICO), Hospital Durán I Reynals, Avda de la Granvia de l’Hospitalet, 199, L’Hospitalet, 08907 Barcelona, Spain
  9. [9] nstitut Català d’Oncologia (ICO), Hospital Universitari Dr. Josep Trueta, Avda França s/n, 17007 Girona, Spain
  10. [10] Present Address: Institut Català d’Oncologia (ICO), Hospital Germans Trias i Pujol, Carretera de Canyet, s/n, Badalona, 08916 Barcelona, Spain
  11. [11] Hospital Universitari de la Vall d’Hebron, Passeig de la Vall d’Hebron, 119, 08035 Barcelona, Spain
  12. [12] Biomedical Research Center, Health Sciences Technology Park, University of Granada, Granada Hospital Complex, 18016 Granada, Spain. Department of Physiology, University of Granada, CIBERFES, IBS, Granada Hospital Complex, 18016 Granada, Spain
  13. [13] Present Address: Ferrer Internacional SA, Avenida Diagonal, 549, 08029 Barcelona, Spain
  14. [14] Spherium Biomed, S.L.U., C/ Joan XXIII, 10, 08950 Esplugues de Llobregat, Spain
  15. [15] Present Address: Ferrer Internacional SA, Avenida Diagonal, 549, 08029 Barcelona, Spain 15 Spherium Biomed, S.L.U., C/ Joan XXIII, 10, 08950 Esplugues de Llobregat, Spain
  16. [16] nstitut Català d’Oncologia (ICO), Hospital Durán I Reynals, Avda de la Granvia de l’Hospitalet, 199, L’Hospitalet, 08907 Barcelona, Spain. Present Address: Institut Català d’Oncologia (ICO), Hospital Germans Trias i Pujol, Carretera de Canyet, s/n, Badalona, 08916 Barcelona, Spain

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• Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 23, Nº. 9, 2021, págs. 1801-1806
• Idioma: inglés
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• Resumen

  • Purpose The objective of this trial was to evaluate the safety and efficacy of melatonin oral gel mouthwashes in the preven- tion and treatment of oral mucositis (OM) in patients treated with concurrent radiation and systemic treatment for head and neck cancer.

    Methods Randomized, phase II, double-blind, placebo-controlled trial (1:1 ratio) of 3% melatonin oral gel mouthwashes vs. placebo, during IMRT (total dose ≥ 66 Gy) plus concurrent Q3W cisplatin or cetuximab. Primary endpoint: grade 3–4 OM or Severe Oral Mucositis (SOM) incidence by RTOG, NCI, and a composite RTOG-NCI scales. Secondary endpoints:

    SOM duration and grade 2–4 OM or Ulcerative Oral Mucositis (UOM) incidence and duration.

    Results Eighty-four patients were included in the study. Concurrent systemic treatments were cisplatin (n = 54; 64%) or cetuximab (n = 30; 36%). Compared with the placebo arm, RTOG-defined SOM incidence was numerically lower in the 3% melatonin oral gel arm (53 vs. 64%, P = 0.36). In patients treated with cisplatin, assessed by the RTOG-NCI composite scale, both SOM incidence (44 vs. 78%; P = 0.02) and median SOM duration (0 vs. 22 days; P = 0.022) were significantly reduced in the melatonin arm. Median UOM duration assessed by the RTOG-NCI scale was also significantly shorter in the mela- tonin arm (49 vs. 73 days; P = 0.014). Rate of adverse events and overall response rate were similar between the two arms.

    Conclusions Treatment with melatonin oral gel showed a consistent trend to lower incidence and shorter SOM duration and shorter duration of UOM. These results warrant further investigation in phase III clinical trial.