Management of Mandibular ORN: PENTO as Medical Treatment

Study Overview
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Brief Summary
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Mandibular osteoradionecrosis, despite its low incidence, remains being the most problematic and irreversible complication after head and neck radiotherapy with no medical treatment to limit or reduce symptoms. Different clinical trials have shown a significant scientific evidence that the treatment with pentoxifylline + tocopherol achieves a certain effectiveness in the treatment of the tissue fibrosis. This study proposes to use this drugs to determine if there is healing of mandibular osteoradionecrosis and/or a symptomatic improvement as well.

Detailed Description
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Mandibular osteoradionecrosis which occurs after the use of radiation therapy for the treatment of head and neck cancer remains being the most problematic and irreversible complication despite its low incidence with no medical treatment to limit or reduce symptoms. Clinical trials conducted to date have shown a significant scientific evidence that the treatment with pentoxifylline + tocopherol achieves a certain effectiveness in the treatment of the tissue fibrosis that have been irradiated based on the properties of this drugs in increased tissue oxygenation and their antioxidant effect. The aim of this study is to determine if there is a clinical improvement of mandibular osteoradionecrosis using Pentoxifylline in combination with Tocopherol as treatment because, currently, there is no effective treatment to achieve bone healing and/or a symptomatic improvement.

Official Title
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Advances in the Management of Mandibular Osteoradionecrosis: Pentoxifylline and Tocopherol as Medical Treatment

Conditions
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Osteoradionecrosis

Intervention / Treatment
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* Drug: Pentoxifylline and Tocopherol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Over 18 years and under 90 years old. Patients who have received radiotherapy after being diagnosed with head and neck cancer and currently are diagnosticated of mandibular osteoradionecrosis (any clinical stage) Follow-up for at least a year after the radiation treatment is completed. Absence of tumor at the time of recruitment. Patients with the capacity to give informed consent Exclusion Criteria: Allergy or hypersensitivity to Pentoxifylline or others xanthines, or to Tocopherol (vitamin E). Patients taking oral anticoagulants (acenocoumarol, warfarin). Known hemorrhagic/coagulation disorder. Vitamin K deficiency due to any cause. Use of estrogens oral contraceptives. Serious bleeding or extensive retinal hemorrhage. Ischaemic heart diseases, including recent Myocardial Infarction. Serious cardiac arrhythmia. Severe LIVER DISEASE. Severe renal failure (creatinine clearance <30 mL/min). Hypotension. Female patients who are pregnant or lactating Any other situation or condition that, in the opinion of the INVESTIGATOR, may interfere with optimal PARTICIPATION in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pentoxifylline and Tocopherol<br>Drug: pentoxifylline with tocopherol Combination of pentoxifylline and tocopherol during a minimum of 6 months and a maximum of 24 months. | Drug: Pentoxifylline and Tocopherol<br>* pentoxifylline with tocopherol Pentoxifylline 800 mg/day, oral (1cp 400 mg twice a day) + Vitamin E (alfa-tocopherol) 1000 UI/day, oral (1cp 400UI twice a day + 1cp200UI once a day) during 24 months (maximum).<br>* Other names: PENTO;|
| No Intervention: CONTROL<br>No drug treatment | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone and/or Tissue Healing as Measured With the Classification of ORN Stages, Area of Bone Exposed (mm2) and Radiological Findings (OPG). | Clinical healing assessment as measured with the classification of ORN stages, area of bone exposed (mm2) and radiological findings (OPG). Intraoral bone exposure is measured in mm2. | From baseline to 1, 3, 6, and 9 months of starting treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Symptoms Evaluation, Measured Using the LENT-SOMA Scale | Evaluation of symptoms improvement using the LENT-SOMA scale (Late Effect Normal Tissue Task Force / Subjective, Objective, Management, Analytic scale). To examine the LENT/SOMA scale prospectively using interviews and questionnaires Assessments were made from baseline to 1, 3, 6 and 9 months of starting treatments. The acceptability and feasibility of using the scales was examined using compliance in completion of the questionnaires. Maximum score: 36 Minimum score: 0 Questionnaires have been completed for 24 patients after treatment. Higher values represents worse outcome. Scale categories: Subjective: pain, nutritional problems, difficulty in mouth openning. Objective: bone exposure, trismus, Management: analgesic treatment, oral treatment, nutrition. Analytic: radiological findings. | From baseline to 1,3, 6, 9 months of starting treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mandible, Mandibular osteoradionecrosis, Tocopherol, pentoxifylline, vitamine E, wounds and injuries, antioxidants, free radical scavengers, radiation-protective agents, vasodilatadors agents, osteonecrosis, extraoral fistula, exposed bone, necrotic bone, head and neck radiotherapy