Phase II trial of high-dose melatonin oral gel for the prevention and treatment of oral mucositis in H&N cancer patients undergoing chemoradiation (MUCOMEL)

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Published on Friday, 13 September 2019

Abstract

Background: Severe Oral Mucositis (SOM) is one of the most significant adverse events (AE) in H&N cancer patients undergoing concurrent chemo/bio-radiotherapy. The objective of the trial is to evaluate the safety and efficacy of melatonin (MLT) oral gel in the prevention and treatment of oral mucositis (OM) in H&N cancer patients.

Methods: Multicenter, prospective, randomized, double-blind, placebo-controlled study. Eligible patients were randomly assigned (1:1 ratio) to receive 3% MLT or matching placebo (PLC) oral gel. Patients received once daily (5 days/week) IMRT radiation therapy (total dose ≥ 66 Gy). Concurrent systemic treatments were cisplatin Q3W or cetuximab Q1W. All patients received concomitant standard symptomatic treatment for OM. Efficacy analyses were performed on a mITT population (patients receiving at least one medication dose) or ITT. Efficacy endpoints were either RTOG or NCI CTCv4, G3-4 oral mucositis (SOM) and G2-4 ulcerative oral mucositis (UOM). Comparison of incidence rates of SOM/UOM: Fisher exact test; comparison of duration of SOM/UOM: U Mann-Whitney test.

Results: 84 patients (ITT: 42 MLT/42PLC; mITT: 40 MLT/39 PLC) were included. Most frequent tumor sites were oropharynx (n = 38; 45%) and oral cavity (n = 24; 29%). Concurrent systemic treatments were cisplatin (n = 54; 64%) or cetuximab (n = 30; 36%). Efficacy results in the mITT population (incidence) and ITT (duration) Clinical trial information: NCT02630004. No relevant differences for AEs between groups or for overall response rate after 2 months of IMRT completion.

Conclusions: Treatment with MLT oral gel resulted in a consistent trend to a lower incidence and shorter duration of SOM as well as a significantly shorter duration of UOM. These benefits were more marked in the subgroup of patients receiving cisplatin. These results warrant further clinical development.

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See also:

- Official Web Site: The Di Bella Method;

- The Di Bella Method (A Fixed Part - Melatonin tablets. From 30-40mg/day up to 200mg/day orally in patients with advanced stage of cancer disease and/or patients without respond to traditional treatments);

- Melatonin with adenosine solubilized in water and stabilized with glycine for oncological treatment - technical preparation, effectivity and clinical findings;

- About Melatonin - In vitro, review and in vivo publications;

- The Di Bella Method (A Fixed Part - Cyclophosphamide 50mg tablets and/or Hydroxyurea 500mg tablets, one or two per day);

- The Di Bella Method DBM improved survival objective response and performance status in a retrospective observational clinical study on 23 tumours of the head and neck;

- Recurrent Glioblastoma Multiforme (grade IV – WHO 2007): a case of complete objective response achieved by means of the concomitant administration of Somatostatin and Octreotide – Retinoids – Vitamin E – Vitamin D3 – Vitamin C – Melatonin – D2 R agonists (Di Bella Method – DBM) associated with Temozolomide;

- The Synergism of Somatostatin, Melatonin, Vitamins Prolactin and Estrogen Inhibitors Increased Survival, Objective Response and Performance Status In 297 Cases of Breast Cancer;

- Complete objective response, stable for 5 years, with the Di Bella Method, of multiple-metastatic carcinoma of the breast;

- Evaluation of the safety and efficacy of the first-line treatment with somatostatin combined with melatonin, retinoids, vitamin D3, and low doses of cyclophosphamide in 20 cases of breast cancer: a preliminary report;

- The Di Bella Method (DBM) improved survival, objective response and performance status in a retrospective observational clinical study on 122 cases of breast cancer;

- Complete objective response to biological therapy of plurifocal breast carcinoma;

- Chronic Lymphocytic Leukemia: Long-Lasting Remission with Combination of Cyclophosphamide, Somatostatin, Bromocriptine, Retinoids, Melatonin, and ACTH;

- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in advanced non-small-cell lung cancer patients with low performance status;

- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in chemotherapy-pretreated patients with advanced lung adenocarcinoma and low performance status;

- Observations on the Report of a case of pulmonary adenocarcinoma with lymph node, hepatic and osseus metastasis;

- Pleural Mesothelioma: clinical records on 11 patients treated with Di Bella's Method;

- Malignant pleural mesothelioma, stage T3-T4. Consideration of a case study;

- Excellent result in a Mesothelioma case treated exclusively with Di Bella Method for over 4 years and still treatment with positive results;

- A case of advanced Multiple Myeloma treated with Di Bella Method (DBM) into total remission for 13 years;

- Neuroblastoma: Complete objective response to biological treatment;

- Cyclophosphamide plus Somatostatin, Bromocriptin, Retinoids, Melatonin and ACTH in the Treatment of Low-grade Non-Hodgkin’s Lymphomas at Advanced Stage: Results of a Phase II Trial;

- Relapse of High-Grade Non-Hodgkin’s Lymphoma After Autologous Stem Cell Transplantation: A Case Successfully Treated With Cyclophosphamide Plus Somatostatin, Bromocriptine, Melatonin, Retinoids, and ACTH;

- Low-grade Non-Hodgkin Lymphoma at Advanced Stage: A Case Successfully Treated With Cyclophosphamide Plus Somatostatin, Bromocriptine, Retinoids, and Melatonin;

- The Di Bella Method (DBM) improved survival, objective response and performance status in a retrospective observational clinical study on 55 cases of Lymphomas;

- Large B-cells Non-Hodgkin's Lymphoma, Stage IV-AE: a Case Report;

- Non-Hodgkin's Lymphoma, Stage III-B-E: a Case Report;

- Oesophageal squamocellular carcinoma: a complete and objective response;

- Pancreatic Adenocarcinoma: clinical records on 17 patients treated with Di Bella's Method;

- The Di Bella Method Increases by the 30% the survival rate for Pancreas tumors and for this reason should be proposed as first line therapy for this type of cancer;

- The Di Bella Method (DBM) in the treatment of prostate cancer: a preliminary retrospective study of 16 patients and a review of the literature;

- Congenital fibrosarcoma in complete remission with Somatostatin, Retinoids, Vitamin D3, Vitamin E, Vitamin C, Melatonin, Calcium, Chondroitin sulfate associated with low doses of Cyclophosphamide in a 14-year Follow Up.