TREATMENT & PATHOGENESIS OF SKIN CANCER, DISORDERS OF CORNIFICATION & PSORIASIS

治疗

• 批准号: 6289038
• 负责人: JOHN J DIGIOVANNA
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6289038
• 关键词: 13 cis retinoate; adolescence (12-20); bone density; bone imaging /visualization /scanning; bone metabolism; cancer prevention; chemoprevention; child (0-11); clinical research; clinical trial phase I; dosage; drug adverse effect; human subject; human therapy evaluation; osteoporosis; phospholipase inhibitor; psoriasis; retinoids; skin disorder chemotherapy; skin neoplasms; topical drug application; vitamin therapy; xeroderma pigmentosum

A study of the efficacy and toxicity of isotretinoin as a chemopreventive agent is being continued in a series of eight patients with xeroderma pigmentosum. Initial results identified an improvement of great magnitude in the rate of new skin cancer formation while on high dose therapy. However, high dose therapy was associated with significant toxicity. Patients continut to be evaluated at intermediate doses in an effort to achieve adequate chemoprevention with minimum toxicity and further define the parameters of isotretinoin chemoprevention. One patient had similar benefit on both low and high dose treatment. Four patients had less improvement on low as compared to high dose treatment. This suggests a dose response. One patient had no benefit from high dose isotretinoin and has been started on a study of oral acitretin, an aromatic retinoid.Osteoporosis has been observed in chronic hypervitaminosis A. We had previously identified decreased bone mineral density in a group of etretinate treated patients. We have continued to study retinoid osteoporosis by evaluating bone mineral densities using DEXA scanning, and continue to valuate bone mineral density and parameters of bone turnover.A phase I/II, double-blind study of topical antiflammin, a phospholipase-A2 inhibitor, for the treatment of psoriasis, is in progress. Fourteen patients have been enrolled at three dose levels and enrollment is continuing.Previous projects evaluating the long-term efficacy and toxicity of the retinoids, isotretinoin and etretinate, in the treatment of the skin cancer, disorders of cornification, and psoriasis have been terminated. - psoriais, retinoid, skin cancer, isotretinoin, acitretin, xeroderma pigmentosum, antiflammin, osteoporosis - Human Subjects

一项关于异维甲酸作为化学预防药物的有效性和毒性的研究正在对一系列8名色素性干皮病患者进行。初步结果表明，在大剂量治疗的情况下，新皮肤癌的形成率有了很大的改善。然而，大剂量治疗与显著的毒性相关。患者继续接受中等剂量的评估，以努力以最小的毒性实现充分的化学预防，并进一步确定异维A酸化学预防的参数。一名患者在低剂量和高剂量治疗中都有类似的益处。与大剂量治疗相比，4名患者在低剂量治疗下的改善较小。这表明这是一个剂量反应。一名患者没有从大剂量异维A酸中获益，并开始了口服维甲酸(一种芳香族维甲酸)的研究。在慢性维生素A增高症中观察到骨质疏松症。我们之前发现一组接受维甲酸酯治疗的患者骨密度降低。我们继续通过使用DEXA扫描评估骨密度来研究视黄样骨质疏松症，并继续评估骨密度和骨转换参数。I/II期，局部应用磷脂酶A2抑制剂安非他明治疗银屑病的双盲研究正在进行中。14名患者参加了三个剂量水平的研究，研究仍在继续。先前评估维甲酸、异维甲酸和乙酸乙酯治疗皮肤癌、角化障碍和牛皮癣的长期疗效和毒性的项目已经终止。-牛皮癣、维甲酸、皮肤癌、异维A酸、阿维A酸、色素性干皮病、安非他明、骨质疏松症-人类受试者