Osteoradionecrosis
Conditions
Keywords
Mandibular osteoradionecrosis, Tocopherol, pentoxifylline, vitamine E, wounds and injuries, antioxidants, free radical scavengers, radiation-protective agents, vasodilatadors agents, osteonecrosis, mandible, extraoral fistula, exposed bone, necrotic bone, head and neck radiotherapy
Brief summary
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
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.
Interventions
DRUGPentoxifylline and Tocopherol
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).
Sponsors
Hospital Vall d'Hebron
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bone and/or Tissue Healing as Measured With the Classification of ORN Stages, Area of Bone Exposed (mm2) and Radiological Findings (OPG). | From baseline to 1, 3, 6, and 9 months of starting treatment | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Symptoms Evaluation, Measured Using the LENT-SOMA Scale | From baseline to 1,3, 6, 9 months of starting treatment | 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. |
Countries
Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pentoxifylline and Tocopherol Drug: pentoxifylline with tocopherol Combination of pentoxifylline and tocopherol during a minimum of 6 months and a maximum of 24 months.
Pentoxifylline and Tocopherol: 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). | 12 |
| Control Group No drug treatment | 12 |
| Total | 24 |
Baseline characteristics
| Characteristic | Pentoxifylline and Tocopherol | Control Group | Total |
|---|---|---|---|
| Age, Continuous | 57 years STANDARD_DEVIATION 10 | 55 years STANDARD_DEVIATION 10 | 56 years STANDARD_DEVIATION 10 |
| Exposed bone | 10 mm^2 STANDARD_DEVIATION 10 | 15 mm^2 STANDARD_DEVIATION 10 | 12.5 mm^2 STANDARD_DEVIATION 10 |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 10 Participants | 10 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 12 | 0 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
Primary
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.
Time frame: From baseline to 1, 3, 6, and 9 months of starting treatment
Population: mean of intraoral bone exposure (measured in mm2) from baseline to 1, 3, 6, 9, 12 and 18 months of starting treatment
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Pentoxifylline and Tocopherol | Bone and/or Tissue Healing as Measured With the Classification of ORN Stages, Area of Bone Exposed (mm2) and Radiological Findings (OPG). | 1 month of starting treatment | 14 mm2 |
| Pentoxifylline and Tocopherol | Bone and/or Tissue Healing as Measured With the Classification of ORN Stages, Area of Bone Exposed (mm2) and Radiological Findings (OPG). | 6 month of starting treatment | 11.5 mm2 |
| Pentoxifylline and Tocopherol | Bone and/or Tissue Healing as Measured With the Classification of ORN Stages, Area of Bone Exposed (mm2) and Radiological Findings (OPG). | 9 month of starting treatment | 10 mm2 |
| Pentoxifylline and Tocopherol | Bone and/or Tissue Healing as Measured With the Classification of ORN Stages, Area of Bone Exposed (mm2) and Radiological Findings (OPG). | 3 month of starting treatment | 13 mm2 |
| Control Group | Bone and/or Tissue Healing as Measured With the Classification of ORN Stages, Area of Bone Exposed (mm2) and Radiological Findings (OPG). | 9 month of starting treatment | 15 mm2 |
| Control Group | Bone and/or Tissue Healing as Measured With the Classification of ORN Stages, Area of Bone Exposed (mm2) and Radiological Findings (OPG). | 3 month of starting treatment | 15 mm2 |
| Control Group | Bone and/or Tissue Healing as Measured With the Classification of ORN Stages, Area of Bone Exposed (mm2) and Radiological Findings (OPG). | 6 month of starting treatment | 15 mm2 |
| Control Group | Bone and/or Tissue Healing as Measured With the Classification of ORN Stages, Area of Bone Exposed (mm2) and Radiological Findings (OPG). | 1 month of starting treatment | 15 mm2 |
Secondary
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.
Time frame: From baseline to 1,3, 6, 9 months of starting treatment
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Pentoxifylline and Tocopherol | Clinical Symptoms Evaluation, Measured Using the LENT-SOMA Scale | 3 month of starting treatment | 14 units on a scale |
| Pentoxifylline and Tocopherol | Clinical Symptoms Evaluation, Measured Using the LENT-SOMA Scale | 1 month of starting treatment | 14.5 units on a scale |
| Pentoxifylline and Tocopherol | Clinical Symptoms Evaluation, Measured Using the LENT-SOMA Scale | 6 month of starting treatment | 14 units on a scale |
| Pentoxifylline and Tocopherol | Clinical Symptoms Evaluation, Measured Using the LENT-SOMA Scale | 9 month of starting treatment | 13.3 units on a scale |
| Control Group | Clinical Symptoms Evaluation, Measured Using the LENT-SOMA Scale | 9 month of starting treatment | 15.5 units on a scale |
| Control Group | Clinical Symptoms Evaluation, Measured Using the LENT-SOMA Scale | 6 month of starting treatment | 15.5 units on a scale |
| Control Group | Clinical Symptoms Evaluation, Measured Using the LENT-SOMA Scale | 1 month of starting treatment | 15.5 units on a scale |
| Control Group | Clinical Symptoms Evaluation, Measured Using the LENT-SOMA Scale | 3 month of starting treatment | 15.5 units on a scale |