Treatment of Radiation-induced Fibrosis in the Upper Aerodigestive Tract Cancer by a Combination of Pentoxifylline-tocopherol and Hyperbaric Oxygen

Study Overview
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Brief Summary
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The pentoxifylline used with tocopherol achieves a certain effectiveness in the treatment of the fibrosis. Hyperbaric oxygen therapy has been recommended and used in a wide variety of medical conditions including the treatment of delayed radiation injuries (soft tissue and bony radiation necrosis). The hyperbaric oxygen therapy increases the formation of granulation tissue and produces angiogenesis maintained after use.

Detailed Description
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Patients with head and neck tumors often present superficial radiation induced fibrosis and other late complications of radiotherapy that can seriously affect their quality of life. The pentoxifylline used with tocopherol achieves a certain effectiveness in the treatment of the fibrosis. Hyperbaric oxygen therapy has been recommended and used in a wide variety of medical conditions including the treatment of delayed radiation injuries (soft tissue and bony radiation necrosis). The hyperbaric oxygen therapy increases the formation of granulation tissue and produces angiogenesis maintained after use. Both treatments in combination could produce a synergistic effect because the angiogenesis induced by hyperbaric oxygen therapy allow better access to drugs to the injury. The magnetic resonance, provides data of the fibrosis and other side effects of radiotherapy.

Official Title
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Treatment of Radiation-induced Fibrosis in the Upper Aerodigestive Tract Cancer by a Combination of Pentoxifylline-tocopherol and Hyperbaric Oxygen

Conditions
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Fibrosis

Intervention / Treatment
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* Drug: pentoxifylline with tocopherol
* Other: pentoxifylline+tocopherol + Hyperbaric Oxygen Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Over 18 years and under 70 years old. Patients who have received radiotherapy after being diagnosed with cancer of upper aerodigestive tract, and have skin toxicity grade II or higher. 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. Patients with metal objects or electronic devices such as cardiac pacemakers, artificial heart valves or cochlear implants, or any other contraindication for MRI Contraindication for Hyperbaric oxygen therapy. Patients with mobility problems. 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

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 |
| --- | --- |
| Active Comparator: Pentoxifylline + Tocopherol<br>Pentoxifylline 800 mg/day (400 mg/12hours) + Tocopherol 1000 mg/day oral during 6 months | Drug: pentoxifylline with tocopherol<br>* Pentoxifylline 800 mg/day (400 mg/12hours) + Vitamin E (alfa-tocopherol) 1000 mg/day,oral during 6 months<br>|
| Experimental: pentoxifylline + tocopherol + Hyperbaric Oxygen Therapy<br> | Other: pentoxifylline+tocopherol + Hyperbaric Oxygen Therapy<br>* pentoxifylline 800 mg/day (400 mg/12hours) + Vitamin E (alfa-tocopherol) 1000 mg/day, oral during 6 months. Hyperbaric Oxygen Therapy at 100% in 25 sessions of 90 minutes 5 days per week (5 weeks) at 2,4 Ata in Hyperbaric chamber, starting in 3 or 9 weeks after randomization and beginning of drug treatment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in skin fibrosis measured by MRI | The change is calculated as the latest time point (6 months) minus the earliest time point (baseline) | From baseline to 6 month of starting treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical assessment of the radiation late (delayed) toxicity for mucosal membranes, salivary glands, larynx and skin by the LENT-SOMA scale (Late Effect Normal Tissue Task Force / Subjective, Objective, Management, Analytic scale) | The change is calculated as the latest time point (6 months) minus the earliest time point (baseline) | Baseline and 6 months |