isotretinoin and Carcinoma

Topics: Aged; Aged, 80 and over; Aminolevulinic Acid; Antineoplastic Agents; Bowen's Disease; Carcinoma; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Evaluation Studies as Topic; Female; Humans; Interferon-alpha; Interferons; Isotretinoin; Keratolytic Agents; Male; Neoplasm Metastasis; Photochemotherapy; Photosensitizing Agents; Retinoids; Skin Neoplasms

An increasing public awareness of antioxidants may prompt a patient's request to be treated without surgery if a leukoplakic lesion is discovered. However, surgical excision remains the treatment of choice for oral leukoplakia. The use of antioxidant supplements has shown some promise, but the predictability of success remains uncertain and long-term results are unavailable. Before the decision to use any antioxidant is made, it is critical to obtain a histopathologic diagnosis of the lesion. When dealing with a lesion diagnosed as hyperkeratosis, it may be appropriate to choose an antioxidant that may take some time for clinical improvement to occur. However, as the grade of epithelial dysplasia becomes more severe, consideration must be given to the possibility of malignant transformation during antioxidant treatment. We do not recommend the use of antioxidant supplements in the treatment of any carcinoma. The therapeutic use of antioxidant supplements outside of clinical trials conducted at academic medical centers should be done with considerable caution by practitioners in private practice. It should be emphasized that in these clinical trial patients were seen at frequent intervals to monitor their progress and to intervene if there was a noticeable deterioration in the clinical appearance of the lesion. In spite of the uncertainty with respect to antioxidant treatment, there are circumstances in which it should be considered. Recurrence after surgical excision when there is little reason to believe that a second surgical excision would be any more successful is an ideal candidate. Also, patients with widespread leukoplakia that involves a large area of the oral mucosa might be suitable for treatment with antioxidants, as well as patients who have extensive medical problems that make them surgical risks. The choice of which antioxidant(s) to use is complex because thus far there is no combination that is superior to the others. Beta-carotene with ascorbic acid or alpha-tocopherol is attractive because of a lack of side effects, but the range in reported values for lesion improvement has been broad and the clinical improvement typically takes several months. Clinical response with 13-cRA is faster but requires baseline and periodic serologic testing, as well as close monitoring for side effects. In those circumstances in which time is an important consideration, 13-cRA might be useful because clinical improvement can be evaluated within a matter of w

Topics: Animals; Antioxidants; Carcinoma; Cell Transformation, Neoplastic; Chemotherapy, Adjuvant; Clinical Trials as Topic; Drug Combinations; Humans; Isotretinoin; Keratolytic Agents; Leukoplakia, Oral; Mouth Neoplasms; Recurrence

We report on a 63-year-old female patient with Muir-Torre syndrome (MTS). In the course of this disease two carcinomas of the colon, a kerato-acanthoma and multiple sebaceous gland tumours, including four sebaceous carcinomas, appeared. This case is thought to be a hereditary form as one of daughters was also found to have a sebaceous epithelioma. MTS is a mostly autosomal-dominant disease with the association of sebaceous gland tumours and internal carcinomas. As the malignant tumours only show slight aggressiveness the prognosis is quite favourable. Oral isotretinoin therapy was successfully used for the inhibition of sebaceous gland proliferation. A narrower definition is presented and an updated survey of the published cases is given. Furthermore, the histopathologic peculiarities of sebaceous gland tumours, especially of sebaceous gland carcinomas, are discussed and compared to sebaceous gland tumours not connected with MTS. A total number of 100 of the 135 published cases of MTS were included and analysed regarding sebaceous gland tumours and other skin tumours. The data on internal carcinomas were taken from the work of Cohen et al. (1991) and 11 current cases were added.

Topics: Adenocarcinoma; Adenoma, Sweat Gland; Adenomatous Polyposis Coli; Administration, Oral; Carcinoma; Carcinoma, Squamous Cell; Chromosome Aberrations; Chromosome Disorders; Diagnosis, Differential; Facial Neoplasms; Female; Genes, Dominant; Humans; Isotretinoin; Keratoacanthoma; Middle Aged; Neoplasm Recurrence, Local; Neoplasms, Multiple Primary; Neoplastic Syndromes, Hereditary; Sebaceous Gland Neoplasms; Sweat Glands; Syndrome

Standard treatment with radiotherapy for locally advanced cancer of the uterine cervix has a response rate of less than 50%. Recently, concurrent chemotherapy with radiotherapy was introduced into the clinic but is value remains controversial. Interferon and retinoic acid possess antiproliferative, immunomodulatory, and antineoplastic activities. The combination of interferon and retinoic acid has significant activity in patients with squamous cell carcinoma. These compounds may also potentiate radiation cytotoxicity. This pilot study aimed to assess the clinical efficacy and tolerability of the combination of interferon-alpha 2a, 13-cis-retinoic acid and radiotherapy. Patients with locally advanced carcinoma of the cervix were treated at Severance Hospital, Yonsei University College of Medicine. Fifteen patients received the combination of interferon-alpha 2a, 13-cis-retinoic acid and radiotherapy. Twelve patients treated in previous years with comparable radiotherapy and concurrent chemotherapy served as historical controls.. (1) Interferon-alpha 2a, 13-cis-retinoic acid and radiotherapy resulted in a 47% response rate (33% complete remissions) while patients treated with concurrent chemoradiotherapy had a 42% response rate (17% complete remissions) (2). Major toxicity of interferon-alpha 2a, 13-cis-retinoic acid and radiotherapy was fever (60%). There was no grade 3 or 4 toxicity.. Systemic interferon-alpha 2a, 13-cis-retinoic acid and radiotherapy is an active and tolerable therapy for locally advanced cervical cancer. Randomized studies are required to define the role of bioradiotherapy in the treatment of advanced cervical cancer.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Female; Humans; Interferon-alpha; Isotretinoin; Middle Aged; Pilot Projects; Radiotherapy, Adjuvant; Treatment Outcome; Uterine Cervical Neoplasms

Combination of two differentiation agents such as phenylbutyrate (PB) and 13-cis-retinoic acid (CRA) has been shown to have an additive inhibitory effect on tumor growth in preclinical studies. In this report we explored the hypotheses that these "cytostatic" agents may have a greater antitumor activity in combination with "cytotoxic" compounds and their biological effect may be sequence-dependent.. The antitumor activity of combination of PB and CRA with paclitaxel (TX ) and doxorubicin (DOXO) on human prostate and colon carcinoma cell lines was assessed both in vitro and in vivo. The effect on cell cycle, apoptotic rate, cyclin expression and induction of p21 expression was also determined.. Following treatment of tumor cells with PB + CRA + TX or DOXO, inhibition of tumor cell growth was greatly enhanced as compared to PB + CRA, TX or DOXO alone, with >90% growth inhibition. However, when the cells were pretreated with PB + CRA followed by TX or DOXO, the enhanced inhibition was abolished suggesting a protective effect to this sequence. Interestingly treatment with PB + CRA restored sensitivity to DOXO in PC-3 human prostate cancer cell line. PB + CRA induced p21 expression and cell-cycle arrest in G1 phase, while TX and DOXO induced G2/M arrest. p21 and p53-deficient colon carcinoma cell lines were more sensitive to the effect of PB + CRA and TX as single agents and in combination, as compared to the wild type cells. When p21-deficient cells were pretreated with PB + CRA followed by TX the protective effect was still observed. Treatment of tumor cells with combination of these drugs induced cell cycle delay at multiple mitotic checkpoints before undergoing apoptosis. Tumor growth was significantly inhibited and delayed in animals treated with either TX or concomitantly with TX and PB + CRA as compared to control. Animals treated with all three agents demonstrated further growth inhibition or delay than the TX alone or PB + CRA arm.. These results suggest a rational therapeutic approach for combination of differentiation-inducing agents with cytotoxic drugs given concomitantly, but not sequentially.

Topics: Antineoplastic Agents; Apoptosis; Carcinoma; Cell Cycle; Cell Differentiation; Cell Division; Cell Line, Tumor; Colonic Neoplasms; Cyclin-Dependent Kinase Inhibitor p21; Cyclins; Flow Cytometry; Humans; Isotretinoin; Male; Phenylbutyrates; Polymerase Chain Reaction; Prostatic Neoplasms

De-differentiated thyroid carcinoma is characterized by loss of thyroid-specific functions and properties. The therapeutic options for this type of thyroid cancer are limited and generally not efficient. Recent studies with retinoic acid (RA) have shown that this drug can induce re-differentiation of the thyrocyte and tumor regression after 131I therapy. The aim of the present study was to assess the effects of RA therapy in patients with extensive thyroid tumor involvement, which lost radioiodine uptake ability. A total of 5 patients (1 follicular carcinoma, 3 papillary carcinomas and 1 poorly differentiated carcinoma) were treated with isotretinoin (1.0 to 1.5 mg/kg/day) for 5 weeks and then submitted to radioiodine therapy. Three parameters for assessment of RA effects were established: a) reduction of serum thyroglobulin levels; b) increment of the post-therapeutic dose radioiodine uptake; c) tumor size regression after therapy. All patients completed the treatment and the most frequent side effects were dry skin and lips and hypertriglyceridemia. One patient showed satisfactory response (2 or more of the 3 criteria were reached) and a new cycle of RA was given. In two, just a partial response (1 criterion) was seen and the other patients did not respond. Based on these results, isotretinoin might be an option for de-differentiated thyroid cancer, with low rate of severe side effects, especially when compared with cytotoxic drugs. Aggressive thyroid cancer frequently needs multimodal adjuvant therapy.

Topics: Adenocarcinoma, Follicular; Adult; Aged; Carcinoma; Carcinoma, Papillary; Female; Humans; Iodine Radioisotopes; Isotretinoin; Male; Middle Aged; Prospective Studies; Radionuclide Imaging; Thyroglobulin; Thyroid Neoplasms; Treatment Outcome

The purpose of this study was to evaluate the synthetic retinoids isotretinoin and etretinate to treat dogs with intracutaneous cornifying epitheliomas (ICE), other benign skin neoplasias, and cutaneous lymphoma. Twenty-four dogs were used. All tumors were diagnosed by histologic examination. Ten dogs with multiple (at least 5) benign skin tumors (7 with ICE, 1 each with inverted papillomas, sebaceous adenomas and epidermal cysts) were treated with isotretinoin (n = 7) and/or etretinate (n = 5). Twelve dogs with cutaneous lymphoma were treated with isotretinoin, and 2 dogs with cutaneous lymphoma were initially treated with etretinate. Successful treatment with isotretinoin was achieved in 1 dog with ICE, 1 with inverted papillomas, and 1 with epidermal cysts. Partial improvement with isotretinoin was seen in 2 dogs with ICE. Successful treatment was achieved with etretinate in 4 dogs with ICE (Norwegian Elkhound was the predominant breed with ICE). Remission was achieved in 6 of the 14 dogs with cutaneous lymphoma. Adverse effects developed in 7 of the 24 dogs, so treatment was stopped in 2 dogs.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Dog Diseases; Dogs; Etretinate; Isotretinoin; Lymphoma; Skin Neoplasms

Previous studies have shown dose-dependent growth inhibition of the human mammary carcinoma cell line MDA-MB-231 xenotransplanted in athymic mice using retinol. In this study, the growth inhibitory effect of retinoic acid (RA) and 13-cis-retinoic acid (13-cis-RA) was examined in vitro and in vivo. With both agents there was dose-related growth inhibition in monolayer culture. The MDA-MB-231 cell line was more sensitive in monolayer culture to 13-cis-RA than to RA. Anchorage-independent growth of the MDA-MB-231 cell line was also inhibited by both of these agents but only in a dose-dependent manner with 13-cis-RA. Athymic mice inoculated with MDA-MB-231 human mammary carcinoma cells were treated with various doses of RA and 13-cis-RA for 30 days. RA doses greater than 90 micrograms were clinically toxic to the animals. There was a decrease in tumor size with all doses of RA tested but not in a dose-related fashion. Response at the higher doses of RA may be related to subclinical toxicity. Doses of 13-cis-RA above 300 micrograms were clinically toxic. Unlike RA, there was no statistically significant decrease in tumor size with treatment with 13-cis-RA. These findings show that there is significant reduction in growth in vivo of the human mammary carcinoma cell line MDA-MB-231 after treatment with RA. However, in vivo response to the retinoids is not always predicted by in vitro methods.

Topics: Animals; Carcinoma; Cell Division; Dose-Response Relationship, Drug; Humans; Isotretinoin; Mammary Neoplasms, Experimental; Mice; Mice, Nude; Neoplasm Transplantation; Retinoids; Transplantation, Heterologous; Tretinoin

Male Syrian golden hamsters received 12 weekly intratracheal exposures to 0.5% N-methyl-N-nitrosourea with a special catheter. Following exposures, animals were randomized into 4 groups of 63 hamsters and placed on diets of lab meal or meal with 120 mg 13-cis-retinoid acid (CRA)/kg, 327 mg ethyl retinamide (ER)/kg, or 343 mg N-(2-hydroxyethyl)retinamide (HR)/kg for 6 months at which time all hamsters were killed. The observed incidences of tracheal epithelial neoplasms (No. of animals with tumors/total No. of animals) were 10/63 (lab meal), 22/61 (CRA), 24/63 (ER), and 17/62 (HR). The incidence of carcinomas (No. of animals with tumors/total No. of animals) were 4/63 (lab meal), 12/61 (CRA), 12/63 (ER), and 11/62 (HR). The weight loss and mortality relative to those in the group fed the lab meal were significantly in the group fed HR but not in the other retinoid-treated groups.

Topics: Amyloidosis; Animals; Carcinoma; Cricetinae; Isotretinoin; Male; Mesocricetus; Methylnitrosourea; Neoplasms, Experimental; Precancerous Conditions; Probability; Tracheal Neoplasms; Tretinoin