Oral mucositis, treatment

The initial trial establishing safety and efficacy was a randomized, placebo-controlled study involving 212 patients. The treated group received 60 pg kg-1 day-1 of the product for 6 days. The primary end-point measured was the number of days during which the patients experienced severe oral mucositis, which treatment reduced from 9 to 3 days. The incidence of mucositis was also reduced from 98 per cent to 63 per cent. 

An example of a simple CZE method for peptide analysis and characterization is the one developed for protegrin IB-367.37 IB-367 is a peptide containing 17 amino acid residues that possess antimicrobial properties, and it is being developed for treatment of oral mucositis associated with aggressive cancer chemotherapy as well as other topical applications. This polycationic product was chemically synthesized using solid-phase and purified by preparative reversed-phase HPLC. IB-367 is rich in cysteine and arginine residues. 

The toxicities of 5-fluorouracil vary with the schedule and mode of administration. Nausea is usually mild if it occurs at all. Myelosuppression is most severe after intravenous bolus administration, with leukopenia and thrombocytopenia appearing 7 to 14 days after an injection. Daily injection or continuous infusion is most likely to produce oral mucositis, pharyngitis, diarrhea, and alopecia. Skin rashes and nail discoloration have been reported, as have photosensitivity and increased skin pigmentation on sun exposure. Neurological toxicity is manifested as acute cerebellar ataxia that may occur within a few days of beginning treatment. 

MALT Mucosal vaccination Mucosal tolerance Nasal/oral inhalation Treatment agent allergies Hyperresponsiveness... 

Wang, J., et al. 2001. Gene gun-mediated oral mucosal transfer of interleukin 12 cDNA coupled with an irradiated melanoma vaccine in a hamster model Successful treatment of oral melanoma and distant skin lesion. Cancer Gene Ther 8 705. 

Buccal tissue is a robust tissue owing to its continuous exposure to a multitude of substances and its high cellular turnover rate.92 93 The absence of Langerhans cells in the oral mucosal tissues reduces sensitivity to potential allergens.94,95 Hence irritation and hypersensitivity reactions due to drugs and their formulation excipients may be minimal in the short term as well as chronic treatment by this route. 

A scoring system for mucositis has been proposed and vahdated (45) and multivariate analysis has been used to identify contributory factors (46). A diagnosis of leukemia, the use of total body irradiation or allogenic transplantation in treatment, or delayed neutrophil recovery were associated with an increased incidence of oral mucositis. 

A 60-year-old man presented with fever, oral mucositis, pedal cellulitis, and bacteremia after a 6-week course of terbinafine 250 mg. He was taking concurrent yohimbine for impotence. Bone marrow examination showed a hypocellular marrow with myeloid maturation arrest. Treatment consisted of withdrawal of outpatient medications, broad-spectrum antibiotics, hydration. 

Powderject was used to deliver dry powdered lidocaine hydrochloride to the oral mucosal surfaces of 14 adult, healthy volunteers in an open, non-randomized, placebo-controlled trial. The delivery caused no visible mucosal damage. The median score for pain on blunt needle probing 1 min after delivery was 10 for the Powderject active sites compared with the score for the placebo sites of 30 and the control sites with no treatment of 58. The results indicated that delivery with the device did not cause tissue damage and was effective in administration of the drug to the site of action. 

Treatment of refractory or recurrent oral mucosal candidiasis (i.e., defined as clinically unresponsive to appropriate antifungal regimen) is frequently unsatisfactory, and clinical response is usually shortlived, with rapid and periodic recurrences. The key risk factors for occurrence of refractory candidiasis are advanced stage of AIDS with low CD4 cell counts (<50 ceUs/mm ) and repeated or prolonged courses of various systemic antifungal agents, in particular... 

AD) as well as the treatment of several cancers, including colon and pancreatic cancers (in combination with agents such as gemcitabine and celebrex), as a chemopreventive agent against colorectal cancer, and in the prevention of oral mucositis in children receiving chemotherapy (http //www.clinicaltrials.gov). 

A successful clinical study was conducted by using limbal-derived cell sheets for the treatment of patients suffering from unilateral total corneal stem-cell deficiencies [18], which resulted from alkali burns or Stevens-Johnson syndrome. In the case of bilateral total comeal stem-cell deficiencies, an autologous oral mucosal epithelial cell sheet was transplanted onto the ocular surface [19]. A clinical trial in France for the treatment of a bilateral limbal stem-cell deficiency had been conducted by using autologous oral mucosal epithelial cell sheets [20]. Through this clinical trial, the treatment was safe and effective in 25 cases with a 1-year follow-up, although two patients experienced serious adverse events, which were not related to the transplantation of the cell sheets. 

Wu SX, Cui TT, Zhao C, Pan JJ, Xu BY, Tian Y, Cui NJ. A prospective, randomized, multi-center trial to investigate Acto-vegin in prevention and treatment of acute oral mucositis caused by chemoradiother-apy for nasopharyngeal carcinoma. Radio-ther Oncol 2010 97(1) 113-8. 

Radtke ML, Kolesar JM (2005) Palifermin (Kepivance) for the treatment of oral mucositis in patients with hematologic malignancies requiring hematopoietic stem cell support. J Oncol Pharm Pract 11 121-125... 

Gravett, P., 2000. Aromatherapy treatment of severe oral mucositis. 10(l-2) 52-53. 

Ohki T, et al. Treatment of oesophageal ulcerations using endoscopic transplantation of tissue-engineered autologous oral mucosal epithehal cell sheets in a canine model. Gut 2006 55 1704-10. 

One other drug, Sativex (GW Pharmaceuticals, London, England) is currently undergoing phase Ilb/ III trials in the USA for the treatment of patients with advanced cancer whose pain is not controlled with opioid medications. The trials were expected to be completed by the end of 2009, after which FDA approval will be sought by the manufacturer to market Sativex in the USA with its partner, Otsuka Pharmaceutical Co. Ltd. Sativex is an oral mucosal spray which delivers a mixture of A -THC and cannabidiol. Cannabidiol is one of the phyto-cannabinoids found in cannabis which has no psychoactivity itself, but reduces the psychoactive side effects of A -THC when... 

The pineal hormone melatonin inhibits the production of free radicals that mediate the toxicity of chemotherapy. The main objective of this prototype drug-deHvery system was to develop and evaluate a novel occlusive bioadhesive system for prophylaxis and/or treatment of oral mucositis based on chitosan, melatonin and propoHs in order to exploit natural biomaterials as functional biocompatible gels [35,40],... 

The newly developed systems behaved in a superior manner to conventional treatment with nystatin emulsion. A positive synergy was observed with a combined antifungal and antioxidant component (synthetic and natural biomaterials) incorporated into a functional biocompatible gel. The in-vitro antioxidant capacity was quantified and the influence of antioxidant capacity of propolis extract on the rate of release of nystatin from chitosan-based material was investigated. These copolymer systems were able to release the drug over several weeks and, therefore, may be useful as a drug carrier in the treatment of oral mucositis [35]. 

V.T. Perchyonok, S. Zhang, T. Oberholzer, Chitosan and gelatin based prototype delivery systems for the treatment of oral mucositis From material to performance in vitro, Curr. DrugDeliv., 10 (1), 144-150, 2013. 

C.E. Saadeh, Chemotherapy- and radiotherapy-induced oral mucositis Review of preventive strategies and treatment, Pharmacotherapy, 25 (4), 540-554,2005. 

Oral mucosal cell sheets are also cfinically applied to the treatment of esophageal ulcerations using an endoscopic transplantation method (Kanai, Yamato, Ohki, Yamamoto, Okano, 2012 Ohki et al., 2006, 2012). Removal of large esophageal cancer tissue section by endoscopic submucosal dissection causes postoperative inflammation and stenosis from a lack of an epithelial layer. After the transplantation... 

Burillon, C., Huot, L., Justin, V., Nataf, S., Chapuis, R, DecuUier, E., et al. (2012). Cultured autologous oral mucosal epithelial cell sheet (CAOMECS) transplantation for the treatment of comeal limbal epithelial stem cell deficiency. Investigative Ophthalmology and Visual Science, 53, 1325-1331. 

Ohki, T., Yamato, M., Murakami, D., Takagi, R., Yang, 1., Namiki, H., et al. (2006). Treatment of oesophageal ulcerations using endoscopic transplantation of tissue-engineered autologous oral mucosal epithelial cell sheets in a canine model. Gut, 55, 1704-1710. 

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