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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.

Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico
September 1, 2021
A Lozano et al. (17 authors)
Clinical Trial, Phase IIJournal ArticleMulticenter StudyRandomized Controlled TrialHuman StudyClinical
Study Details

Study Goal

The researchers aimed to evaluate the safety and efficacy of 3% melatonin oral gel mouthwashes in preventing and treating oral mucositis in head and neck cancer patients undergoing concurrent radiation and systemic treatment.

Results Summary

Melatonin oral gel showed a trend toward lower incidence and shorter duration of severe oral mucositis, particularly in cisplatin-treated patients, with significant reductions in some endpoints. Adverse event rates were similar between melatonin and placebo arms.

Population

Head and neck cancer patients receiving concurrent radiation and systemic treatment (cisplatin or cetuximab).

Effective Dosage

3% melatonin oral gel mouthwashes.

Duration

Duration of IMRT (total dose ≥66 Gy) plus concurrent systemic treatment.

Interactions

None mentioned.

Extracted Claims (6)
InterventionDirectionEndpointPopulationDosageImpactClaim #
3% melatonin oral gel mouthwashes
decrease
RTOG-defined Severe Oral Mucositis (SOM) incidence
patients treated with concurrent radiation and systemic treatment for head and neck cancer
53 vs. 64%
numerically lower
#1
3% melatonin oral gel mouthwashes
decrease
SOM incidence
patients treated with cisplatin
44 vs. 78%
significantly reduced
#2
3% melatonin oral gel mouthwashes
decrease
median SOM duration
patients treated with cisplatin
0 vs. 22 days
significantly reduced
#3
3% melatonin oral gel mouthwashes
decrease
median Ulcerative Oral Mucositis (UOM) duration
patients treated with concurrent radiation and systemic treatment for head and neck cancer
49 vs. 73 days
significantly shorter
#4
3% melatonin oral gel mouthwashes
no change
rate of adverse events
patients treated with concurrent radiation and systemic treatment for head and neck cancer
-
similar
#5
3% melatonin oral gel mouthwashes
no change
overall response rate
patients treated with concurrent radiation and systemic treatment for head and neck cancer
-
similar
#6
Abstract

PURPOSE: The objective of this trial was to evaluate the safety and efficacy of melatonin oral gel mouthwashes in the prevention 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 melatonin 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.

Medical Subject Headings (MeSH)
Administration, OralAdultAgedAged, 80 and overAntineoplastic AgentsAntioxidantsCetuximabChemoradiotherapyCisplatinDouble-Blind MethodFemaleGelsHead and Neck NeoplasmsHumansIncidenceMaleMelatoninMiddle AgedMouthwashesPlacebosProof of Concept StudyProspective StudiesStomatitis
Study Links
Quality Scores
Safety80
Efficacy75/10
Quality85/10
Citation Metrics
Total Citations27
Citations/Year6.8
Relative Citation Ratio2.70
NIH Percentile82.6%
Research Impact Scores
APT Score0.75
Weight Score2.76
Normalized Score0.79
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