tretinoin and Leukoplakia--Oral

The aim of the current study was to evaluate, in an open trial, the clinical efficacy of topical calcipotriol compared with tretinoin in the therapy of hyperkeratotic oral lesions (leukoplakia). The study group consisted of 40 patients with histologically proven oral leukoplakias, 20 treated with calcipotriol, the other 20 with tretinoin. The treatment was for 5 weeks and follow-up at 4 months, with clinical assessments at 2, 4 and 5 weeks and regular laboratory assessments. The results showed a significant reduction in lesions (80%), in both calcipotriol and tretinoin groups, with no documented topical or systemic adverse reactions, results maintained at 4 months. Tretinoin however, potentially can induce erythema, angular cheilitis and xerostomia. The study suggests that topical calcipotriol is as effective in the therapy of oral leukoplakia as is topical tretinoin.

Topics: Administration, Topical; Adult; Antineoplastic Agents; Calcitriol; Female; Humans; Leukoplakia, Oral; Male; Middle Aged; Treatment Outcome; Tretinoin

Inhibition of buccal pouch carcinogenesis induced by dimethyl-benzanthracene in hamsters with retinamide was studied. Group A received oral retinamide at a dosage of 20mg/kg, every day for eight weeks. Group B was treated by retinamide orally at the same dosage, plus topical treatment by retinamide. Group C was treated by retinamide topically for eight weeks. Experiments exhibited that under the action of retinamide the incidence of tumor was lowered significantly. All the Group A, B and C had a good response. Clinically 80 patients were randomly arranged into two groups. One group received placebo and served as controls and the other group was treated by retinamide. Results indicate that retinamide is effective against leukoplakia and the response rate is as high as 84.0%. By contrast, only 16.7% of patients receiving placebo showed some improvement.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Adult; Aged; Animals; Antineoplastic Agents; Cricetinae; Female; Humans; Leukoplakia, Oral; Male; Middle Aged; Tretinoin

In earlier work, we demonstrated that 0.1 p. 100 topical tretinoin is clinically effective and well tolerated compared with placebo for the treatment of oral leukoplakia and oral keratosic or erythematous lichen planus. Here we aimed to complete this clinical protocol with histological and biochemical analyses comparing the biopsy specimens collected at inclusion and those collected after 4 months of treatment. Histological results were based on changes in keratinization observed between onset of treatment and 4 months treatment. Biochemical studies included the use of antibodies (anti-cytokeratins 10-11, anti-filaggrine) for the immunohistochemical evaluation of keratinization and 2-dimensional gel electrophoresis for measuring cytokeratins. In patients with lichen planus, histological changes during treatment showed that, in the 10 patients in the tretinoin group, keratinization disappeared in 6 and decreased significantly in 3. Immunohistochemistry revealed that cytokeratins 10-11 and filaggrin disappeared in 57 p. 100 of the patients treated with tretinoin versus 25 p. 100 in the patients given placebo. Bidimensional gel electrophoresis showed that cytokeratins 1, 2, 10 and 11 disappeared only in the tretinoin group (60 p. 100 of the cases). In patients with leukoplakia, histological changes during treatment showed that, in the tretinoin group, keratinization disappeared in 5 cases and decreased in 5 others. Immunohistochemistry revealed that cytokeratins 10-11 disappeared in 30 p. 100 of the patients treated with tretinoin versus 25 p. 100 in the placebo group. Bidimensional electrophoresis demonstrated that cytokeratins 1, 2, 10 and 11 disappeared in 43 p. 100 of the patients treated with tretinoin.

Topics: Administration, Topical; Electrophoresis, Gel, Two-Dimensional; Filaggrin Proteins; Humans; Immunohistochemistry; Keratins; Leukoplakia, Oral; Lichen Planus, Oral; Mouth Mucosa; Treatment Outcome; Tretinoin

A randomized study was conducted to evaluate the effect of tretinoin and patient tolerance to treatment with topical applications in series of 20 cases of smoking-related or traumatic oral keratoses leukoplakia and of 20 cases of lichen planus. In each group, patients applied the topical ointment containing tretinoin (10 patients) or placebo (10 patients) twice daily. Clinical outcome was evaluated on the basis of the surface area of the lesion, measured monthly during treatment, as compared with the area observed at treatment onset. After 4 months treatment, there was a significant decrease in the surface area of the lesion in the patients with lichen planus (p < 0.02): 94 p. 100 in the tretinoin group versus 21.4 p. 100 in the placebo group. In patients with leukoplakias, there was also a very significant reduction in the surface area of the lesion after 4 months of treatment (p < 0.001): 80 p. 100 in the tretinoin group and 16 p. 100 in the placebo group. Tolerance to treatment was generally good despite a few complaints of quite temporary burning sensation at application rapidly resolutive.

Topics: Administration, Topical; Aged; Double-Blind Method; Drug Evaluation; Drug Tolerance; Female; Humans; Leukoplakia, Oral; Lichen Planus, Oral; Male; Middle Aged; Mouth Mucosa; Treatment Outcome; Tretinoin

Topics: beta Carotene; Carotenoids; Dose-Response Relationship, Drug; Humans; Leukoplakia, Oral; Neoplasms; Tretinoin

Mucosal dysplasia in the head and neck region is recognized to be a precancerous lesion. Between January 1983 and December 1987, a pilot study was conducted at the Manitoba Cancer Treatment and Research Foundation to determine the effects of beta-carotene and cis-retinoic acid on mucosal dysplasias. Eighteen patients were treated with a "cross-over" regimen. The overall response to treatment was 61%, with 33.3% complete responses. Patients who smoked had a significantly better response than nonsmokers. The response rate for 9 of 11 smokers was 81.2%, and 2 of 7 nonsmokers or 28.6% responded to this protocol. The beneficial effect of these drugs should be established by prospective, randomized trial in high risk populations.

Topics: Adult; Aged; Aged, 80 and over; beta Carotene; Carotenoids; Drug Evaluation; Erythroplasia; Female; Humans; Leukoplakia, Oral; Lichen Planus; Male; Middle Aged; Mouth Diseases; Mouth Mucosa; Pilot Projects; Precancerous Conditions; Prospective Studies; Smoking; Tretinoin; Vitamin A

13-cis-Retinoic acid has been reported to be effective in treating oral leukoplakia. We randomly assigned 44 patients with this disease to receive 13-cis-retinoic acid (24 patients) or placebo (20), 1 to 2 mg per kilogram of body weight per day for three months, and followed them for six months. There were major decreases in the size of the lesions in 67 percent (16 patients) of those given the drug and in 10 percent (2 patients) of those given placebo (P = 0.0002); dysplasia was reversed in 54 percent (13 patients) of the drug group and in 10 percent (2 patients) of the placebo group (P = 0.01). The clinical response to the drug correlated with the histologic response in 56 percent (9 of 16) of the patients evaluated. Relapse occurred in 9 of 16 patients two to three months after treatment ended. The toxic effects of the drug were acceptable in all but two patients. Cheilitis, facial erythema, and dryness and peeling of the skin were common; conjunctivitis and hypertriglyceridemia also occurred. All adverse reactions could be reversed by reducing the dose or temporarily discontinuing the drug. We conclude that 13-cis-retinoic acid, even in short-term use, appears to be an effective treatment for oral leukoplakia and has an acceptable level of toxicity.

Topics: Aged; Clinical Trials as Topic; Female; Humans; Isotretinoin; Leukoplakia, Oral; Male; Middle Aged; Random Allocation; Tretinoin

The effects of the vitamin A-derived aromatic retinoid (Ro 10-9359) on 25 patients with oral hyperkeratosis were good. Compared with vitamin A, toxicity is reduced and the recurrence quota after discontinuation of the preparation is lower.

Topics: Capsules; Clinical Trials as Topic; Etretinate; Female; Follow-Up Studies; Humans; Leukoplakia, Oral; Male; Middle Aged; Mouth Mucosa; Time Factors; Tretinoin

Experiences in the treatment of lichen planus mucosae (including the erosive type) are reported. Good therapeutical results could be obtained in all patients. Leukoplakic patches showed a partial involution and in some cases erosive alterations healed completely. After interruption of medication a relapse was observed in most cases. Concerning side effects, some patients complained in particular of minor dryness of both labial and nasal mucosa and of diffuse hair effluvium.

Topics: Adult; Aged; Clinical Trials as Topic; Drug Evaluation; Etretinate; Female; Humans; Leukoplakia, Oral; Lichen Planus; Male; Middle Aged; Mouth Diseases; Mouth Mucosa; Recurrence; Time Factors; Tretinoin

Topics: Administration, Topical; Antineoplastic Agents; Diabetes Mellitus, Type 2; Humans; Leukoplakia, Oral; Male; Middle Aged; Treatment Outcome; Tretinoin

Topics: Aged; Antineoplastic Agents; Carcinoma, Verrucous; Female; Follow-Up Studies; Humans; Laser Therapy; Lasers, Gas; Leukoplakia, Oral; Neoplasms, Second Primary; Tongue Neoplasms; Tretinoin; Wound Healing

Retinoic acid receptor-beta(2) (RAR-beta(2)) expression is suppressed in oral premalignant lesions and head and neck squamous cell carcinomas (HNSCCs). This study was conducted to determine whether RAR-beta(2) gene expression in such lesions can be silenced by promoter methylation.. RAR-beta(2) methylation was analyzed in DNA samples from 22 pairs of primary HNSCC and adjacent normal epithelium, 124 samples of oral leukoplakia, and 18 HNSCC cell lines using methylation-specific PCR. RAR-beta(2) promoter was methylated in 67, 56, and 53% of HNSCC tumors, HNSCC cell lines, and microdissected oral leukoplakia specimens, respectively. RAR-beta(2) hypermethylation was confirmed by sodium bisulfite-PCR combined with restriction enzyme digestion analysis and by random cloning and sequencing of bisulfite-treated DNA isolates.. Significantly higher RAR-beta(2) hypermethylation levels were found in tumor tissue compared with adjacent normal tissue (P = 0.002). RAR-beta(2) methylation in the cell lines was correlated with loss of RAR-beta(2) expression (P = 0.013) and inversely related to the presence of mutated p53 (P = 0.025). The demethylating agent 5-aza-2'-deoxycytidine (5-aza-CdR) restored RAR-beta(2) inducibility by all-trans-retinoic acid (ATRA) in some of the cell lines, which posses a methylated RAR-beta(2) promoter. In some cell lines, this effect was associated with increased growth inhibition after combined treatment with 5-aza-CdR and ATRA.. RAR-beta(2) silencing by methylation is an early event in head and neck carcinogenesis; 5-Aza-CdR can restore RAR-beta(2) inducibility by ATRA in most cell lines, and the combination of 5-aza-CdR and ATRA is more effective in growth inhibition than single agents.

Topics: Adult; Aged; Aged, 80 and over; Base Sequence; Carcinoma, Squamous Cell; Cell Division; Cell Line, Tumor; Cloning, Molecular; DNA Methylation; DNA Primers; DNA, Neoplasm; Female; Gene Silencing; Head and Neck Neoplasms; Humans; Leukoplakia, Oral; Male; Middle Aged; Molecular Sequence Data; Mouth Neoplasms; Polymerase Chain Reaction; Precancerous Conditions; Promoter Regions, Genetic; Receptors, Retinoic Acid; Tretinoin

Pachyonchia congenita (PC) is an uncommon autosomal dominant genodermatosis affecting the nails and other ectodermal tissues. The most striking features are symmetrically thickened dysmorphic nails and hyperkeratotic skin lesions. We report a case of pachyonychia congenita in a 30-year-old male patient who had thickening and gray-brown discoloration of all nails and many nodules on his back and neck. He also had hyperkeratotic skin lesions on both feet. His tongue had irregularly-shaped, whitish plaques. Histology of these nodules revealed the characteristic features of steatocystoma multiplex. After treatment with oral retinoic acid, his hyperkeratotic skin lesions improved.

Topics: Adult; Ectodermal Dysplasia; Epidermal Cyst; Humans; Keratoderma, Palmoplantar; Leukoplakia, Oral; Male; Nails, Malformed; Prognosis; Tretinoin

Topics: Humans; Keratolytic Agents; Leukoplakia, Oral; Tretinoin

Deficiency of vitamin A and/or its precursors has been associated with increased cancer risk in animals and humans. Therapeutic trials of vitamin A and related compounds have demonstrated activity in several cancerous and precancerous conditions. The authors measured the effects of a retinoid, 13-cis-retinoic acid, and a carotenoid, beta-carotene, on the human immune system in vivo in conjunction with their use in ongoing clinical trials. Immune cell subpopulations were analyzed by quantifying the expression of markers using flow cytometric study. Both compounds produced significant effects on immune cell populations. 13-cis-Retinoic acid resulted in an increase in the percentage of peripheral blood lymphoid cells expressing surface markers for T-helper cells with only minimal effect on natural killer cell marker expression. In contrast, beta-carotene produced an increase in the percentage of cells expressing natural killer cell markers with smaller effect on T-helper markers. Modest increases in the percentage of cells expressing Ia antigen, transferrin, and interleukin-2 receptors were produced by both drugs. These results suggest that retinoids and carotenoids can produce major changes in immune cellular marker expression in vivo in humans at doses relevant to their potential clinical use.

Topics: Adult; Aged; Barrett Esophagus; beta Carotene; Carotenoids; Humans; Immunity, Cellular; Killer Cells, Natural; Leukoplakia, Oral; Male; Middle Aged; T-Lymphocyte Subsets; T-Lymphocytes; T-Lymphocytes, Helper-Inducer; Tretinoin

Topics: beta Carotene; Carotenoids; Diet; Humans; Leukoplakia, Oral; Neoplasms; Tretinoin

Oral hairy leukoplakia was treated in six patients with (a) acyclovir (i.v. or p.o.), (b) 0.1% vitamin-A acid solution or (c) human beta-interferon-gel (10(5) I.E./g) in a total of 23 therapeutic courses. In 5/6 patients, acyclovir (7.5 mg/kg every 8 h i.v. or 5 x 400 mg p.o. over 5-10 days) led to partial (n = 1) or complete (n = 4) remission. After 1-6 months, however, the leukoplakia recurred in all cases. Vitamin-A acid solution (n = 3) led to remission in one and to improvement in the others. Human beta-interferon gel (n = 3) had no visible effect. The efficacy of acyclovir is further evidence of the concept that the Epstein-Barr virus is a major cause of oral hairy leukoplakia.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Administration, Oral; AIDS-Related Complex; Drug Therapy, Combination; Humans; Infusions, Intravenous; Interferon Type I; Leukoplakia, Oral; Mouth Mucosa; Neoplasm Staging; Tretinoin

This two phase study was designed to observe the toxicity and effectiveness of retinoids on oral leukoplakia. The study design included patients who had visible and measurable oral leukoplakia without history of synchronous oral cancer or oral cancer within the previous 2 years. Documentation of the lesion by direct measurement and photography, as well as a biopsy at the beginning and at the end of the study (for verification of the histologic appearance of the lesion), were performed in each patient. Sixteen patients with oral leukoplakia were treated with 13-cis-retinoic acid formulated in a troche in the strength of 1 mg. Three patients received 3 mg/day, 8 patients received 5 mg/day, and 5 patients received 10 mg/day. The initial visible responding event appeared to be a thinning of the leukoplakia with reduction in the whitish surface leaving a reddish, velvety epithelium. If resolution occurred, the velvety area became pink, assuming the color and texture of the normal adjacent mucosa. Toxicity of the drug appeared to be acceptable among the evaluable patients. Of the 11 patients, 3 demonstrated complete response and 6 demonstrated partial response after 6 months of treatment with the drug under study. Recurrences developed in two of the three patients with complete response, and neither of the two showed complete histologic and cytologic regression. One of the patients with partial response went on to complete response after cessation of treatment. Under the condition of our study, a treatment effect was observed with small amounts of topical 13-cis-retinoic acid and that the level of toxicity was acceptable.

Topics: Administration, Topical; Dose-Response Relationship, Drug; Drug Evaluation; Humans; Isomerism; Isotretinoin; Leukoplakia, Oral; Tablets; Time Factors; Tretinoin

Sixty-four male and female Syrian hamsters, 3 months of age and weighing 90 to 120 grams, were divided into four equal experimental groups. In animals of Groups 1 and 2 the right posterior lateral border of the tongue was painted three times weekly with a 0.5 percent solution of DMBA in acetone. Group 2 animals also received 10 mg. of 13-cis-retinoic acid in peanut oil administered orally twice weekly by pipette. Carcinogen and retinoid were administered on alternate days. Group 3 animals received only 13-cis-retinoic acid. Group 4 animals served as untreated controls. Four animals in each group were killed at 12, 14, 16, and 18 weeks. The Group 2 animals, receiving 13-cis-retinoic acid, exhibited a significant delay in the development of lingual tumors, both grossly and microscopically. At 14 weeks carcinomas were found in the DMBA animals, but only dysplasia and areas of carcinoma in situ were found in the DMBA-retinoid animals. After 18 weeks the DMBA animals exhibited large lingual tumors with surfacenecrosis, while the DMBA-retinoid animals presented smaller tumors with less invasion of underlying tissue.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinoma, Papillary; Carcinoma, Squamous Cell; Cricetinae; Female; Isotretinoin; Leukoplakia, Oral; Male; Mesocricetus; Neoplasms, Experimental; Tongue; Tongue Neoplasms; Tretinoin

Sixty-four male and female Syrian hamsters, 3 months of age and weighing 90 to 120 grams, were divided into four equal experimental groups. In animals of Groups 1 and 2 the left buccal pouch was painted three times weekly with a 0.5% solution of DMBA in heavy mineral oil. Group 2 animals also received 10 mg. of 13-cis-retinoic acid in peanut oil administered orally twice a week by pipette. Carcinogen retinoid were administered on alternate days. Group 3 animals served as controls, receiving only 13-cis-retinoic acid. Group 4 animals served as untreated controls. Four animals in each group (two males and two females) were killed at 10, 12, 14, and 16 weeks. The Group 2 animals, which received 13-cis-retinoic acid, exhibited a significant delay in DMBA carcinogenesis of buccal pouch mucosa, as studied both grossly and histologically. Both groups eventually demonstrated well-differentiated epidermoid carcinomas, but the tumors were smaller in the DMBA-retinoid animals.

Topics: Animals; Carcinoma, Papillary; Carcinoma, Squamous Cell; Cheek; Cricetinae; Female; Isotretinoin; Keratosis; Leukoplakia, Oral; Male; Mesocricetus; Mouth Mucosa; Mouth Neoplasms; Neoplasms, Experimental; Tretinoin

Topics: Administration, Topical; Adult; Aged; Female; Humans; Leukoplakia, Oral; Lichen Planus; Male; Middle Aged; Mouth Diseases; Mouth Mucosa; Recurrence; Tretinoin

Topics: Adult; Aged; Drug Evaluation; Female; Humans; Leukoplakia, Oral; Male; Middle Aged; Recurrence; Tretinoin

Leukoplakia is neither a clinical, aetiological nor histopathological entity. Therefore treatment is difficult particularly in multifocal and advanced lesions. Since 1970, we have tested the therapeutic effect of different derivatives of all-trans-retinoic acid. The study includes 75 cases with homogeneous leukoplakia without or with minimal epithelial dysplasia. Over 60% of the cases treated showed positive early results. In follow-ups from 1 to 6 years about 45% of cases showed complete or partial remission. The rest showed relapses or even progression. In cases with recurrence without changes in the morphological characteristics, positive effects were achieved with 1 to 4 repeated courses of therapy. All derivatives of retinoic acid tested so far have shown undesirable side effects with systematic manifestations or local symptoms: interruption of treatment (4) or reduction of dosage (9) were unavoidable for that reason. Regarding the side effects, retinoic acid should only be given under clinical supervision. Of the derivates tested to date, aromatic retinoid seems to have the best curative potential in homogenic leukoplakia.

Topics: Humans; Leukoplakia, Oral; Mouth Neoplasms; Precancerous Conditions; Recurrence; Tretinoin; Vitamin A

Vitamin A acid (VAS) has proved itself an effective local therapeutic agent for intra-oral leucoplakia. Clinical remission characterized by a decrease in horny lumps and the eosinophilic index and an increase in intermediary cells was achieved in 32 out of 50 cases. In the course of maintenance therapy development towards an exfoliocytologically healthy mucosa proceeds via increasing parakeratosis. VAS therapy is essentially thought of as symptomatic therapy.

Topics: Administration, Topical; Cytological Techniques; Female; Humans; Leukoplakia, Oral; Male; Middle Aged; Mouth Mucosa; Tretinoin; Vitamin A

Topics: Follow-Up Studies; Humans; Leukoplakia, Oral; Male; Middle Aged; Tretinoin; Vitamin A