tretinoin and Cheilitis

All-trans retinoic acid (ATRA), a potent differentiating drug for acute promyelocytic leukemia (APL), induces a high incidence of complete remission (CR) in patients with APL and is now established as a first-line therapy. However, ATRA resistance has become a clinical problem. Patients who relapsed after ATRA-induced CR have had difficulty in obtaining a second CR with ATRA therapy. Although several mechanisms have been postulated, treatment strategies to overcome resistance have not been established. We used a new synthetic retinoid, Am-80, as reinduction therapy for APL relapse after from ATRA-induced CR. Am-80 was several times more potent than ATRA in inducing differentiation in vitro. At a 6 mg/m2 dose, there were 24 evaluable patients; 14 (58%) achieved CR between days 20 and 58 (median, 37 days). Clinical response correlated with the in vitro response to Am-80. Adverse effects included retinoic acid syndrome (n = 1), hyperleukocytosis (n = 1), xerosis (n = 9), cheilitis (n = 8), hypertriglyceridemia (n = 16), and hypercholesterolemia (n = 15). Am-80 is active in APL after relapse from ATRA-induced CR. Further clinical trials are needed to establish strategies to overcome ATRA resistance.

Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Arsenicals; Benzoates; Biomarkers, Tumor; Cheilitis; Cytarabine; Daunorubicin; Disease-Free Survival; Drug Resistance, Neoplasm; Female; Humans; Hypercholesterolemia; Hypertriglyceridemia; Leukemia, Promyelocytic, Acute; Leukocytosis; Male; Middle Aged; Neoplasm Proteins; Oncogene Proteins, Fusion; Pilot Projects; Recurrence; Remission Induction; Salvage Therapy; Tetrahydronaphthalenes; Treatment Outcome; Tretinoin; Tumor Cells, Cultured

The evaluation of new therapies in prostate cancer requires unique end points for agents with diverse mechanisms of action. Because retinoic acid may have a confounding effect on prostate-specific antigen, we incorporated a pathological end point into the outcome assessment of two sequential clinical trials using all-trans-retinoic acid (ATRA) and the combination of 13-cis-retinoic acid and IFN-2a (cRA¿IFN). Pre- and posttherapy tumor biopsy specimens were studied for histological changes, apoptosis (terminal deoxynucleotidyl transferase-mediated nick end labeling assay), and proliferation index (Ki67). Prostate-specific membrane antigen (PSMA) expression was also evaluated using two different monoclonal antibodies to its intracellular domain (Cytogen 7E11 and Hybritech PM2). Fourteen patients with androgen-independent disease were treated with ATRA (50 mg/m2 p.o. every 8 h daily) and 16 androgen-independent and 4 androgen-dependent patients were treated with cRA¿IFN (10 mg/kg/day cRA plus 3, 6, or 9 million units daily IFN). Both therapies were well tolerated, with fatigue and cheilitis being the most common adverse events. Clinical activity, assessed by radiographs and serum prostate-specific antigen, was minimal, and the majority of patients progressed within 3 months. One patient with androgen-dependent disease had prolonged stabilization for >1 year. The majority of cases (95%) showed no gross histological changes and no difference in apoptotic or proliferative indices. Increased PSMA immunoreactivity was seen in seven of nine (78%) cases using PM2 antibody and in two of nine (22%) cases using the 7E11 antibody. Although antitumor effects were modest, the results suggest a role for retinoids in modulating the expression of PSMA on prostate cancer cells.

Topics: Aged; Antigens, Surface; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Bone Neoplasms; Carboxypeptidases; Cheilitis; Dyspnea; Exanthema; Fatigue; Glutamate Carboxypeptidase II; Hematologic Diseases; Humans; Interferon alpha-2; Interferon-alpha; Ki-67 Antigen; Liver; Male; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Recombinant Proteins; Transaminases; Treatment Outcome; Tretinoin

9-cis-Retinoic acid (9-cis-RA) has a particular pattern of binding and activating retinoid receptors. Treatment of chronic hand eczema is often refractory to conventional treatment.. Evaluation of oral 9-cis-RA therapy in chronic hand eczema in a pilot study.. Thirty-eight patients with refractory chronic hand eczema were treated in an exploratory open-label study with oral 9-cis-RA.. Twenty-one (55%) showed a very good response, 13 (34%) a good response, 2 (5.5%) a moderate response and 2 (5.5%) no response. Side effects were mild.. 9-cis-RA is a valuable drug when given at low doses to patients with chronic hand eczema.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Alitretinoin; Antineoplastic Agents; Cheilitis; Chronic Disease; Eczema; Female; Flushing; Hand Dermatoses; Headache; Humans; Male; Middle Aged; Patient Satisfaction; Pilot Projects; Severity of Illness Index; Skin; Treatment Outcome; Tretinoin

All-trans retinoic acid (ATRA), a potent differentiating drug for acute promyelocytic leukemia (APL), induces a high incidence of complete remission (CR) in patients with APL and is now established as a first-line therapy. However, ATRA resistance has become a clinical problem. Patients who relapsed after ATRA-induced CR have had difficulty in obtaining a second CR with ATRA therapy. Although several mechanisms have been postulated, treatment strategies to overcome resistance have not been established. We used a new synthetic retinoid, Am-80, as reinduction therapy for APL relapse after from ATRA-induced CR. Am-80 was several times more potent than ATRA in inducing differentiation in vitro. At a 6 mg/m2 dose, there were 24 evaluable patients; 14 (58%) achieved CR between days 20 and 58 (median, 37 days). Clinical response correlated with the in vitro response to Am-80. Adverse effects included retinoic acid syndrome (n = 1), hyperleukocytosis (n = 1), xerosis (n = 9), cheilitis (n = 8), hypertriglyceridemia (n = 16), and hypercholesterolemia (n = 15). Am-80 is active in APL after relapse from ATRA-induced CR. Further clinical trials are needed to establish strategies to overcome ATRA resistance.

Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Arsenicals; Benzoates; Biomarkers, Tumor; Cheilitis; Cytarabine; Daunorubicin; Disease-Free Survival; Drug Resistance, Neoplasm; Female; Humans; Hypercholesterolemia; Hypertriglyceridemia; Leukemia, Promyelocytic, Acute; Leukocytosis; Male; Middle Aged; Neoplasm Proteins; Oncogene Proteins, Fusion; Pilot Projects; Recurrence; Remission Induction; Salvage Therapy; Tetrahydronaphthalenes; Treatment Outcome; Tretinoin; Tumor Cells, Cultured

Prompted by recent demonstrations that all-trans-retinoic acid (all-trans-RA) had efficacy in acute promyelocytic leukemia, a phase I trial of all-trans-RA was conducted to establish the maximum-tolerated dose (MTD) before phase II testing.. Forty patients with a histologic or cytologic diagnosis of malignancy other than leukemia were treated with single daily oral doses of all-trans-RA ranging from 45 mg/m2 to 200 mg/m2. Doses of all-trans-RA were escalated in the next cohort of patients until the MTD was determined if the preceding dose level was not associated with significant toxicity.. Lung cancer was the most common type of tumor included in the study (26 cases) followed by head and neck squamous cell carcinomas (three cases), and squamous cell carcinoma of the skin (two cases); other miscellaneous solid tumors were also represented. Toxicities included cheilitis, skin reactions, headache, and nausea and vomiting, as well as transient elevations of liver enzymes and triglyceride levels. Skin toxicities, consisting of erythema with desquamation and paronychia, were considered to be the dose-limiting toxicity, and were observed in two of six patients who received 175 mg/m2/d, and in two of five patients who received 200 mg/m2/d. Of the 30 patients with assessable lesions, response was evaluated in 26 patients and no major objective tumor response was observed. Two patients were able to receive the drug for longer than 1 year without significant toxicities. There was considerable variation in individual patients' peak plasma all-trans-RA levels, and a decrease in the area under the curve of all-trans-RA plasma concentration was observed in all four patients evaluated.. For phase II study of adult patients, we recommend 150 mg/m2 of all-trans-RA administered orally once a day. However, for better optimization of drug administration schedules, further studies are needed.

Topics: Adult; Aged; Alkaline Phosphatase; Cheilitis; Chemical and Drug Induced Liver Injury; Dose-Response Relationship, Drug; Female; Headache; Hearing Disorders; Humans; Liver; Liver Diseases; Male; Middle Aged; Nausea; Neoplasms; Skin Diseases; Tretinoin; Vomiting

Acitretin, a metabolite of etretinate, was given to 38 patients for the treatment of psoriasis. During the first 8 weeks patients received either placebo, 10 mg, 25 mg, 50 mg, or 75 mg of acitretin daily in a double-blind manner. The dosages of 10 mg and 25 mg daily did not achieve any statistically significant improvement in psoriasis over placebo; however, both the 50 and 75 mg dosages were statistically significantly better than placebo. Side effects were primarily mucocutaneous and occurred in most patients receiving 25 mg or more of acitretin daily. After the double-blind period, patients continued treatment in an open fashion until they had received a total of 24 weeks of acitretin therapy. Most patients received 50 mg of acitretin daily, which adequately cleared their psoriasis. After approximately 3 months without acitretin, most patients required retreatment. Subsequent 24-week courses of therapy were generally effective and well tolerated. The most common laboratory abnormalities were elevations of triglyceride, cholesterol, and liver transaminase levels. The efficacy and side effects of acitretin appear to be similar to those of etretinate; the principal advantage of acitretin is its shorter half-life. Although acitretin is a potent teratogen, its rapid elimination makes it a viable treatment for psoriasis among women of childbearing potential.

Topics: Acitretin; Adult; Cheilitis; Clinical Trials as Topic; Dose-Response Relationship, Drug; Double-Blind Method; Humans; Psoriasis; Tretinoin

Thirty patients with treatment-resistant cystic and conglobulate acne entered a randomized double-blind protocol, testing the efficacy of isotretinoin versus tetracycline. After 16 weeks of isotretinoin treatment, the mean number of cysts decreased by 64% and the mean sum of the longest diameters was reduced by 68%. After 16 weeks of tetracycline therapy, the total number of cysts showed a mean decrease of 52%, and the mean sum of the longest diameters decreased by 60%. The reduction in the number of cysts and the sum of their longest diameters that occurred after 16 weeks of treatment was statistically significant for each of the treatment groups, but there was no statistically significant difference between the treatment groups at the end of therapy. Eight weeks after the discontinuation of treatment in the isotretinoin group, there was an overall reduction from baseline of 82% in the cyst count and 88% in the sum of the longest diameters. In the tetracycline treatment group, the overall reduction from baseline in the cyst count was 54% and in the sum of the longest diameters, 60%. This led to a statistically significant difference in the two treatment groups at 24 weeks. All patients on isotretinoin experienced side effects that were primarily related to the integumentary system but necessitated discontinuation of the drug for a short period of time in only one patient. Long-term follow-up, 8 months after discontinuation of the study, showed a prolonged significant remission of acne in the isotretinoin group but not in the tetracycline group.

Topics: Acne Vulgaris; Adolescent; Adult; Cataract; Cheilitis; Clinical Trials as Topic; Double-Blind Method; Epistaxis; Female; Follow-Up Studies; Humans; Isomerism; Isotretinoin; Male; Random Allocation; Tetracycline; Tretinoin; Xerophthalmia; Xerostomia

Exfoliative cheilitis (EC) is a rare inflammatory condition affecting the vermilion of the lips and characterized by production of a thick keratin scale. Given the limited available data, the approach to optimal management of EC remains unclear. The objective of this retrospective study was to characterize the clinical features, management, and outcomes of a series of patients with EC. Fifteen patients with a median age of 59 years and a female-to-male ratio of 2:1 were diagnosed with EC from 2000 to 2010. Parafunctional lip licking (53%) and a history of psychiatric disorders (40%) were common. Ten patients (66%) returned for follow-up, with an overall response rate (partial or complete) of 80% at a median of 2 months, most frequently associated with the use of topical calcineurin inhibitors or moisturizing agents. Management of EC with topical calcineurin inhibitors and moisturizing agents is associated with clinical improvement, but prospective trials are needed.

Topics: Adrenal Cortex Hormones; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Biopsy; Cheilitis; Dermatologic Agents; Emollients; Female; Humans; Keratolytic Agents; Male; Middle Aged; Mupirocin; Petrolatum; Photomicrography; Retrospective Studies; Tacrolimus; Tretinoin

A 67-year-old Japanese woman who presented with erythema on the abdomen and pancytopenia was found to have acute promyelocytic leukemia (APL). A skin biopsy revealed invasion of APL cells. She was started on induction treatment with all-trans retinoic acid (ATRA) at 45 mg/m(2). On day 4, the leukemic cell number had increased to over 1.0 x 10(9)/L. Consequently, chemotherapy with idarubicin and cytarabine was initiated. On day 10, dryness of the lips appeared. The lower lip swelled and developed painful black eschars. A high fever was also present. Despite discontinuing ATRA on day 20 and administering antibiotics, an anti-fungal agent and valaciclovir, these signs did not improve. Histopathologically, the biopsied lip revealed infiltration of neutrophils and vasculitis. The patient was given ATRA on days 29 and 30 due to an increase in APL cell numbers, after which the gangrenous cheilitis extended over the whole lip. On day 49, the patient was started on re-induction treatment with arsenic trioxide. She achieved complete remission and the gangrenous cheilitis slowly healed over the following 8 weeks. Since the clinical features of the gangrenous cheilitis in this case were similar to those of ATRA-associated scrotal ulcers, it appears that activated neutrophils derived from differentiated APL cells may have caused the gangrenous cheilitis. Physicians should be alert to the development of gangrenous cheilitis during treatment with ATRA.

Topics: Aged; Antineoplastic Agents; Arsenic Trioxide; Arsenicals; Biopsy; Cheilitis; Female; Gangrene; Humans; Leukemia, Promyelocytic, Acute; Oxides; Tretinoin

Topics: Administration, Topical; Cheilitis; Humans; Photosensitivity Disorders; Tretinoin

13 patients of both sexes, affected by a severe form of papular rosacea, were treated with 13-cis retinoic acid (1 mg/kg/day) for 2 months. One patient interrupted the treatment after 15 days because of severe blepharitis. The size and number of papules were progressively reduced from the 2nd week, reaching complete regression at the 6th week. Three patients complained of mild blepharitis, 9 patients developed dry cheilitis.

Topics: Adult; Aged; Blepharitis; Cheilitis; Drug Eruptions; Drug Evaluation; Female; Humans; Isotretinoin; Male; Middle Aged; Rosacea; Tretinoin; Triglycerides

Twenty-eight patients with severe acne and one with hidradenitis suppurativa and acne were treated for 12 to 16 weeks with a new synthetic retinoid, isotretinoin (Roaccutane). The average dose was 0.56 mg/kg/day. Patients were seen weekly for four weeks and then fortnightly for the remaining treatment period, being evaluated both qualitatively and quantitatively. Twenty-five patients had an excellent response. Two to five months after the end of treatment no patient had relapsed. No patient withdrew because of side effects, but all suffered dry lips. This study confirms the potential of isotretinoin in the treatment of severe acne.

Topics: Acne Vulgaris; Acute Disease; Adult; Capsules; Cheilitis; Drug Evaluation; Female; Follow-Up Studies; Humans; Isotretinoin; Male; Time Factors; Tretinoin

One female patient 18 years old who suffers from Congenital Uaquioniquis since infancy, with serious alterations of nails, was treated with oral retinoid (Ro 10-9359-Tigason) during 20 months, with clinical improvement of her lesions. Clinical and laboratory controls were carried out periodically and they did not show any alterations. The only side-effects were itching, discrete hair loss headache, chelitis, all which were moderate in degree and transient.

Topics: Administration, Oral; Adolescent; Alopecia; Cheilitis; Etretinate; Female; Humans; Nail Diseases; Tretinoin

A phase I study of 13-cis-retinoic acid was done in 16 patients with head and neck malignancies using a modified Fibonacci search scheme, with individual doses ranging from 20 to 120 mg/m2. Drug doses greater than 60 mg/m2 induced intense headaches, urethritis, desquamative dermatitis, vertigo, and ataxia. The severity of these side effects precludes the use of 13-cis-retinoic acid as a potential chemopreventive agent at doses greater than 60 mg/m2.

Topics: Adult; Aged; Cheilitis; Dose-Response Relationship, Drug; Drug Evaluation; Female; Head and Neck Neoplasms; Headache; Humans; Ichthyosis; Isomerism; Male; Middle Aged; Tretinoin; Urethritis

A new synthetic oral retinoid, 13-cis retinoic acid, is fairly well tolerated in patients and appears to be effective in those with Darier's disease and lamellar ichthyosis. It is less effective in those with pityriasis rubra pilaris. The mechanism of action of 13-cis retinoic acid in disorders of keratinization is unknown at the present time; however, it does not appear to cause lysosomal proliferation in therapeutic doses.

Topics: Adolescent; Adult; Cheilitis; Child; Conjunctivitis; Darier Disease; Dose-Response Relationship, Drug; Evaluation Studies as Topic; Female; Humans; Ichthyosis; Isotretinoin; Male; Middle Aged; Pityriasis Rubra Pilaris; Tretinoin

An aromatic retinoid (Ro-10/9359) was used for oral treatment of five cases of ichthyosis (three lamellar, two X-linked. Complete clearing of the skin lesions was achieved in all five patients within 24.2 +/- 3.2 days (X-linked 21.75 +/- 6.5, lamellar 23 days). Histopathology showed reduction of the hyperkeratosis, and thickening of the granular layer. Clinical side effects were of mild intensity and included cheilitis, conjunctivitis and pruritus. All side effects were reversible upon reduction of the daily dosage. In three patients treatment was discontinued after clearing of lesions. Fresh lesions re-appeared 6 weeks later. One patient with X-linked ichthyosis developed two recurrences during maintenance treatment; one patient with lamellar ichthyosis was kept in complete remission for 9 weeks on a reduced daily dosage.

Topics: Adolescent; Cheilitis; Child; Child, Preschool; Female; Humans; Ichthyosis; Male; Skin; Tretinoin; Vitamin A

The aromatic retinoic acid derivative Ro 10-9359 was administered orally to 25 severe psoriatic patients (14 with generalized plaques, 7 erythrodermic, 4 pustular). The initial dose was 25 mg/20 kg body weight daily for 4 weeks; afterwards the same posology was given every other day during several months (Max : 18 months). Excellent results were obtained in 16 patients (64 p. 100) particularly in severe erythrodermic and pustular psoriasis. However, under follow-up therapy relapses sometimes occurred leading to temporary resumption of initial posology. The most important side effects are cheilitis, palmoplantar scaling with thinning of the skin, hyperhidrosis and diffuse hair loss. A slight increase of transaminases and of alkaline phosphatases was found in a few patients. The Ro 10-9359 compound is a very useful new therapy of severe psoriasis.

Topics: Administration, Oral; Adult; Alkaline Phosphatase; Alopecia; Cheilitis; Female; Humans; Hyperhidrosis; Male; Psoriasis; Transaminases; Tretinoin; Vitamin A

Thirteen patients with keratinising dermatoses were treated for 2-17 weeks with oral 13-cis retinoic acid. There was near complete clearing of the skin lesions beginning within 2 weeks of starting treatment in all five patients with lamellar ichthyosis (including two cases of non-bullous congenital ichthyosiform erythroderma), in two of the three patients with Darier's disease, and in one patient with pityriasis rubra pilaris. The patients with psoriasis and naevus comedonicus did not improve. The main form of toxicity was cheilitis. These results indicate that 13-cis retinoic acid may be more effective and is less toxic than naturally occurring retinoic acid (all-trans vitamin A acid), and that the synthetic retinoids may represent a potent new class of drugs in the treatment of cutaneous disease.

Topics: Administration, Oral; Adult; Cheilitis; Child; Child, Preschool; Darier Disease; Drug Evaluation; Female; Follow-Up Studies; Humans; Ichthyosis; Male; Middle Aged; Pityriasis Rubra Pilaris; Skin Diseases; Tretinoin; Vitamin A