|Year : 2015 | Volume
| Issue : 2 | Page : 291-294
Efficacy of oxitard capsules in the treatment of oral submucous fibrosis
Santosh Patil1, BS Santosh2, Sneha Maheshwari3, Abhijeet Deoghare1, Satish Chhugani1, PR Rajesh4
1 Department of Oral Medicine and Radiology, Chattisgarh Dental College and Research Institute, Rajnandgaon, Chattisgarh, India
2 Department of Oral and Maxillofacial Surgery, Chattisgarh Dental College and Research Institute, Rajnandgaon, Chattisgarh, India
3 Dental Practitioner, Jodhpur, Rajasthan, India
4 Endodontics and Conservative Dentistry, Chattisgarh Dental College and Research Institute, Rajnandgaon, Chattisgarh, India
|Date of Web Publication||7-Jul-2015|
Dr. Santosh Patil
Department of Oral Medicine and Radiology, Chattisgarh Dental College and Research Institute, Rajnandgaon - 491 441, Chattisgarh
Source of Support: None, Conflict of Interest: None
Aim: Oral submucous fibrosis (OSMF) is a high-risk premalignant condition predominantly seen in the Indian subcontinent. The aim of the present study was to evaluate the efficacy of oxitard capsules in the management of OSMF.
Materials and Methods: Total of 120 subjects with clinico-pathologically diagnosed OSMF were included in the study and divided equally in 2 groups; Group A (oxitard group) and Group B (placebo group). Group A was administered 2 oxitard capsules twice daily and Group B was given placebo tablets twice daily, for 3 months. Evaluation for different clinical parameters was done at regular intervals and data was analyzed using the Student's paired t test and Chi-square test. P < 0.001 was considered to be statistically significant.
Results: Clinical improvements in mouth-opening and tongue protrusion were significant in the Group A (P < 0.001). Subjective symptoms of burning sensation (P = 0.0001), pain associated with the lesion (P = 0.000), difficulty in swallowing (P = 0.0003) and speech (P = 0.0005) also significantly improved in the Group A. There was a mild to moderate decrease in the size of the lesion.
Conclusion: Though there is no definitive treatment for the condition; however, oxitard capsules can bring about significant clinical improvements in the symptoms like mouth-opening, tongue protrusion, burning sensation, difficulty in swallowing and speech and pain associated with the lesion, thereby improving the quality of life of the affected individuals.
Keywords: Antioxidants, mouth opening, oral submucous fibrosis, oxitard capsules
|How to cite this article:|
Patil S, Santosh B S, Maheshwari S, Deoghare A, Chhugani S, Rajesh P R. Efficacy of oxitard capsules in the treatment of oral submucous fibrosis. J Can Res Ther 2015;11:291-4
|How to cite this URL:|
Patil S, Santosh B S, Maheshwari S, Deoghare A, Chhugani S, Rajesh P R. Efficacy of oxitard capsules in the treatment of oral submucous fibrosis. J Can Res Ther [serial online] 2015 [cited 2019 Nov 22];11:291-4. Available from: http://www.cancerjournal.net/text.asp?2015/11/2/291/136023
| > Introduction|| |
Oral submucous fibrosis (OSMF) is a potentially malignant disorder of oral cavity, pharynx and upper digestive tract, characterized by progressive inability to open the mouth and by inflammation and progressive fibrosis of the submucosal tissues.  Pindborg and his associates defined the condition as "an insidious chronic disease affecting any part of the oral cavity and sometimes pharynx. Although occasionally preceded by and/or associated with vesicle formation, it is always associated with juxtaepithelial inflammatory reaction followed by fibroelastic changes in the lamina propria, with epithelial atrophy leading to stiffness of the oral mucosa causing trismus and difficulty in eating."  Susrutha in ancient medicine described a condition similar to OSMF as "vidari", under the umbrella of mouth and throat diseases.  In 1952, Schwartz described a condition of the oral mucosa as "atrophia idiopathica mucosa oris", with the term OSMF coined by Joshi in 1953. , The pathogenesis of the disease is not well known, but the etiology is believed to be multifactorial. The condition is particularly associated with areca nut chewing, which is the main component of betel quid. The habit of betel quid chewing is practiced predominately in the Indian subcontinent from a long time. 
Treatment modalities for relieving the symptoms have been advocated, but have not been successful so far. The first step of preventive measure should be in discontinuation of habit, which can be encouraged through education, counseling and advocacy and to maintain proper oral hygiene. Medical treatment is symptomatic and predominantly aimed at improving mouth movements. Specific treatment includes administration of steroids, placental extracts, interferon (IFN) gamma, pentoxifylline, lycopene, surgical excision, etc. But each treatment has its own limitations. ,
Oxitard has been successfully tried in the treatment of OSMF by Singh et al.  The aim of the present study was to evaluate and compare the efficacy of oxitard capsules with a placebo in conjunction with the cessation of the causative habit of the most prevalent and challenging disease of the Indian subcontinent.
| > Materials and Methods|| |
The present prospective study included 120 subjects with clinico-pathologically diagnosed OSMF reporting to the Department of Oral Medicine and Radiology. Patients of either sex with OSMF were included in the study. Those with any evidence of severe psychiatric, cardiac, gastrointestinal or metabolic disorders and pregnancy and lactation were excluded from the study. Ethical clearance was obtained from the Institutional Ethical Committee. A written informed consent was obtained from the patients prior to the inclusion in the study. Detailed family and medical history with the history of associated habits, and the course of the disease was recorded. A thorough clinical examination was carried out and relevant findings were recorded. The subjects were randomly divided equally in 2 groups; Group A (oxitard group) and Group B (placebo group). Group A was administered 2 oxitard capsules twice daily and Group B was given placebo tablets twice daily, for 3 months. Mouth opening was measured by measuring the distance between the center of incisal edges of maxillary central incisors and mandibular central incisor at the maximum opened mouth. In edentulous patients, the inter ridge (alveolar) distance along the midline was measured.  Three measurements were recorded consecutively and the average value was calculated and recorded. Tongue protrusion was measured as distance between mesial contact area of lower central incisor and tip of the tongue on protrusion with a metal grade scale.  Evaluation for presence, absence or reduction of other clinical parameters such as burning sensation, pain associated with the lesion, difficulty in swallowing and speech and variation in the size of the lesion was done at regular intervals of 1 month, 2 month and 3 months. The clinical parameters such as burning sensation, pain associated with the lesion, difficulty in swallowing and speech were evaluated by using a Visual Analog Scale (VAS). The score of 0-1 was considered as absent, score in range of 1-6 was considered as reduced and a score of 7-10 was evaluated as present. The data was entered using computer software, the Statistical Package for the Social Sciences (SPSS version 12.0, SPSS Inc., Chicago, USA) and analyzed using the Student's paired t test and Chi-square test. P < 0.001 was considered to be statistically significant.
| > Results|| |
There were 64 males and 56 females with a mean age of 31.6 ± 12.7 years. Of these, 56% of the patients had the habit of betel nut chewing, whereas 26% of the patients had tobacco-chewing habit. Forty percent of the patients consumed spicy foods, which were among the main causative factors for OSMF in the study population. Clinical improvements in mouth opening and tongue protrusion were significant in the Group A (P < 0.001) [Table 1] and [Table 2]. The effect of administration of oxitard capsules in the Group A showed significant improvement in the subjective symptoms of burning sensation (P = 0.0001), pain associated with the lesion (P = 0.000), difficulty in swallowing (P = 0.0003) and speech (P = 0.0005) when compared with Group B [Table 3], [Table 4], [Table 5] and [Table 6]. There was a mild to moderate decrease in the size of the lesion. Total of 19 patients from Group A and 7 patients from Group B showed a severe degree of change in the size of the lesion, i.e., a decrease of >2.5 cm. Total of 21 patients from Group A and 18 patients from Group B showed a moderate (1.5-2.5 cm) change in the size of the lesion at the end of the study. Total of 15 patients from Group A and 25 patients from Group B showed a mild (0-1.5 cm) change in the size of the lesion. However, 5 patients from Group A and 10 patients from Group B showed no change in the lesion size over the study period. Eight patients experienced mild abdominal discomfort due to the drug. None of the patients withdrew from the study due to any reason.
|Table 1: Effect of oxitard in improving mouth opening (mean values in mm)|
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|Table 2: Effect of oxitard in improving tongue protrusion (mean values in mm)|
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| > Discussion|| |
OSMF is a precancerous condition of the oral cavity and oropharynx, which is predominantly seen in the Indian subcontinent and Southeast Asian countries and is now globally considered an Indian disease. The overall prevalence rate in India is believed to be about 0.2% to 0.5% and prevalence by gender varying from 0.2-2.3% in males and 1.2-4.57% in females. , It is considered to have a high degree of malignant potential, which ranges between 2.3% and 7.6%.  The pathophysiology of OSMF is complex, and various factors such as, ingestion of chilies, genetic susceptibility, nutritional deficiencies, altered salivary constituents, autoimmunity and collagen disorders may be involved in the pathogenesis.  Areca nut and its products are the most common etiological factors. The condition is preceded by burning sensation of the oral mucosa, ulceration and pain. OSMF is characterized by blanching of oral mucosa, reduced movement and depapillation of tongue, depigmentation of oral mucosa, and progressive reduction of mouth opening. , Nasal twang due to fibrosis of nasopharynx and hearing impairment due to stenosis of Eustachian tube More Details may be observed in advanced stages of the condition.
Majority of OSMF patients present with irreversible moderate-to-severe condition. The changes of OSMF are limited to oral tissues and similar to those of scleroderma. It may be associated with oral leukoplakia and other potentially malignant disorders or with malignancy such as squamous cell carcinoma.  The precancerous nature of OSMF has been proved by, higher occurrence of OSMF in oral squamous cell carcinoma patients, histological diagnosis of cancer without any clinical suspicion in OSMF, high frequency of epithelial dysplasia and higher prevalence of leukoplakia among OSMF. The debate over the initiation of malignancy in OSMF due to epithelium or due to connective tissue is still unanswered. , However, it has been suggested that the pathology develops within the epithelium due to intraoral trauma and various factors such as, irritation from jagged teeth, sharp overhanging restoration, ill-fitting dentures, jacket crowns, prolong use of tobacco and poor oral hygiene. ,
Arecoline, an active alkaloid found in betel nuts, stimulates fibroblasts to increase production of collagen by 150%.  Arecoline has been found to elevate the mRNA and protein expression of cystatin C, a non-glycosylated basic protein consistently upregulated in a variety of fibrotic diseases, in a dose-dependent manner in persons with oral submucous fibrosis.  Keratinocyte growth factor-1, insulin like growth factor-1, and interleukin 6 expressions, which have all been implicated in tissue fibrogenesis, were also significantly upregulated in persons with oral submucous fibrosis and arecoline may be responsible for their enhanced expression. , Further studies have shown that arecoline is an inhibitor of metalloproteinases (particularly metalloproteinase-2) and a stimulator of tissue inhibitor of metalloproteinases, which decreases the overall breakdown of tissue collagen.  Flavanoid, catechin, and tannin in betel nuts cause collagen fibers to cross-link, making them less susceptible to collagenase degradation resulting in increased fibrosis by causing both increased collagen production and decreased collagen breakdown. , Areca nuts have also been shown to have a high copper content, and by chewing areca nuts for 5-30 minutes significantly increases soluble copper levels in oral fluids, which upregulates copper-dependent lysyl oxidase activity.  Oral submucous fibrosis remains active even after cessation of the chewing habit.
Treatment modalities for relieving the symptoms have been advocated, but have not been successful so far. The first step of preventive measure should be in advising the patient to discontinue the habit of betel nut chewing, tobacco, spicy foods and chilies. This can be encouraged through education, counseling and advocacy. Medical treatment is symptomatic and predominantly aimed at improving mouth movements. But, each treatment has its own limitations. According to Caniif et al., the medical management of OSMF is both empirical and unsatisfactory.  According to Rehana et al. multiple minerals and micronutrients showed significant improvement in mouth opening of 41% of the patients, similar to the results of the present study.  Whereas, Borle et al. showed improvement in symptoms of OSMF but insignificant improvement in mouth opening with vitamin A, in contrast with oxitard capsules, which showed significant improvement in mouth opening as well as in symptoms of burning sensation, pain associated with the lesion, difficulty in speech and swallowing.  Lycopene has also showed significant improvement in mouth opening in the study by Karemore et al. similar to the findings of the present study.  Sudarshan et al., have shown significant improvement in the mouth opening with aloe vera, similar to that observed with oxitard in the present study.  Sudarshan et al. showed an improvement of 80% in burning sensation in the aloe vera group whereas 65.7% patients showed in the antioxidant group showed improvement in burning sensation.  This difference was statistically significant (P = 0.008), similar to the findings of the present study where the difference in the improvement in both the groups was also statistically significant (P = 0.0001). Newer drugs pentoxyfilline and spirulina have also showed promising results in the treatment of OSMF similar to oxitard, with statistically significant results (P = 0.000) in mouth opening, burning sensation and tongue protrusion by Mulk et al.  Mehrotra et al. also observed significant improvement in total sign and symptom score with the administration of 400 mg pentoxifylline to 32 patients for a period of 7 months.  Singh et al. have shown significant improvement in mouth opening, hyperkeratosis, pain in mouth and size of the lesion with oxitard capsules.  However, the present study evaluated the efficacy of the drug in the improvement of other clinical parameters such as, difficulty in swallowing, speech, tongue protrusion and burning sensation when compared with a control group.
The formulation of the oxitard capsules contains the extracts of Mangifera indica, Withania somnifera, Daucus carota, Glycyrrhiza glabra, Vitis vinifera, powders of Emblica officinalis and Yashada bhasma, and oils of Triticum sativum. Glycyrrhiza glabra normalizes the hoarseness in voice and has immunomodulatory and anti-inflammatory properties. Vitis vinifera have anti-inflammatory, astringent and an effect to curb the burning sensation. Triticum sativum is a rich source of minerals and has an antioxidant property. Withania somnifera provides overall health and wellness with its anti-stress, anti-anxiety, anti-inflammatory, anti-convulsive and anti-arthritic properties. Emblica officinalis is a rich source of vitamin C and is a potent antibiotic. Yashada bhasma contains zinc, which plays a significant role in protein synthesis, cell division and wound healing. Daucus carota acts as a good antiseptic as it is a rich source of vitamin A. Mangifera indica is shown to have antibiotic, anti-asthmatic, antiseptic, antiviral, hypotensive, anti-emetic properties. 
The findings of the present study were similar to the findings of Singh et al. who showed a significant improvement in mouth opening, pain of the mouth, hyperkeratosis and size of the lesion.  However, the present study evaluated the efficacy of oxitard capsules in the improvement of various other clinical parameters such as, tongue protrusion, difficulty in swallowing and speech and burning sensation when compared with the control group. Changes in the severity of burning sensation, difficulty in swallowing and speech and pain were noted, but were poorly defined in the absence of a recognized and validated pain scale.
| > Conclusion|| |
The findings of the present study demonstrates that oxitard capsules significantly improve the mouth opening, tongue protrusion, burning sensation, pain associated with the lesion, difficulty in swallowing and speech, with very few side effects. However, it does not bring about any significant changes in the size of the lesion. Larger sample size, with longer period of treatment and follow-up are encouraged.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]