PentoxIfylline and Tocopherol for the Treatment of Post-radiotherapy Fibrosis in Head and Neck Cancer Patients

Inclusion Criteria:

* Subjects aged ≥18 years at the time of signing the Informed Consent Form
* Subjects with diagnosis of radiotherapy-induced fibrosis of the head and neck: trismus and/or dysphagia as defined by the following patient-centred criteria: Trismus: "Does your mouth opening feel restricted" (answer must be yes). Dysphagia: a score of 3 or more on the 10-item Eating Assessment Tool (EAT-10)
* Previous History of Head \& Neck Cancer
* Previous radiotherapy to the Head \& Neck - minimum 50 Gy completed at least 12 months before screening visit
* No history of primary cancer resection and/or reconstructive surgery to anatomical areas involved in swallowing and/or chewing with potential for altered and reconstructed muscular anatomy that may not be amenable to exercise/respond to anti-fibrotic medications (with the exception of diagnostic biopsy/tonsillectomy and neck lymphadenectomy)
* Cancer-free for a minimum of 12 months after completion of radiotherapy, (complete clinical/radiological remission; absence of distant metastases)
* Able to understand the purpose of the study and willing to sign informed consent.
* Able to take study medications orally
* Subjects of child bearing potential/potency must adhere to one method of highly effective contraception.
* Subject has provided written informed consent
* Diagnosis of RIF of the head and neck by patient defined criteria:
* Trismus: "Does your mouth opening feel restricted?" Dysphagia: a score of 3 or more on the 10-item Eating Assessment Tool (EAT-10)29
* No history of primary cancer resection and/or reconstructive surgery to anatomical areas involved in swallowing and/or chewing with potential for altered and reconstructed muscular anatomy that may not be amenable to exercise/respond to antifibrotic medications (with the exception of diagnostic biopsy/tonsillectomy and neck dissections)
* Able to take study medications orally
* Subjects of child-bearing potential/potency must adhere to one method of highly effective contraception

Exclusion Criteria:

* Concomitant presence of other disorders that may cause trismus or dysphagia (e.g. active temporomandibular joint disorder limiting mouth opening, scleroderma, oral sub mucous fibrosis or other rheumatological or neurological disease)
* Subject has recurrent H\&N cancer or second primary H\&N cancer
* Subject has a known hypersensitivity to pentoxifylline or other xanthines such as caffeine, theophylline and theobromine or tocopherol (vitamin E).
* Subject has a history of acute porphyrias (acute intermittent porphyria, variegate porphyria, hereditary coproporphyria and 5-aminolaevulinic acid dehydratase deficiency porphyria)
* Subject has a history of cerebral haemorrhage, extensive retinal haemorrhage or is at risk of increased bleeding including those taking anticoagulants and platelet aggregation inhibitors such as: clopidogrel, eptifibatide, tirofiban, epoprostenol, iloprost, abciximab, anagrelide, NSAIDs other than selective COX-2 inhibitors, acetylsalicylates (ASA/LAS), ticlopidine, dipyridamole
* Subject has a history of acute myocardial infarction, coronary artery disease, cardiac arrhythmias
* Subject has a active/ongoing hypotension
* Subject has a active/ongoing hepatic or renal impairment
* Subject has a history of diabetes
* Expected non-compliance with treatment interventions or is considered unsuitable for trial participation at the discretion of the treating clinician.
* Current pregnancy as confirmed by urine pregnancy test at screening.
* Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency.
* Subjects with osteoradionecrosis of the jaw.
* Breastfeeding mothers
* Subjects with a MIO of \<12mm
* Recurrent H\&N cancer or second primary H\&N cancer
* History of cerebral haemorrhage, extensive retinal haemorrhage or is at risk of increased bleeding (including those taking anticoagulants and platelet aggregation inhibitors)
* History of acute myocardial infarction, severe coronary artery disease, severe cardiac arrhythmias
* History of hepatic or renal impairment
* Expected non-compliance with treatment interventions or is considered unsuitable for trial participation at the discretion of the treating clinician
* Rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency