CHEMOPREVENTION OF SKIN CANCER--DFMO PHASE 3 TRIAL

描述：(申请者描述)大约80万个新皮肤 美国每年都会发生癌症，这是对 我们的医疗保健系统。皮肤癌已被证明与紫外线有关 曝光量。在发生的关键生化变化中，多胺 生物合成一直与肿瘤的促进有关。干扰 通过抑制鸟氨酸脱羧酶(ODC)生物合成多胺 含有二氟甲基鸟氨酸(DFMO)的酶可减少皮肤癌的形成。 DFMO已被证明能抑制佛波酯诱导的ODC，应用于 人的皮肤。 该提案被设计为DFMO的第三阶段研究。第一步将是 一项为期4周的安慰剂磨合研究，在334名受试者中评估依从性和 剔除不符合规定的人(估计为15%)。第二步是 284例DFMO的安慰剂对照双盲随机研究(Est.) 有基底细胞或鳞状细胞皮肤癌病史的受试者。 受试者将随机服用安慰剂或DFMO，平均为期4年 (3-5年)。在治疗期间，大约40%的受试者将 预计会患上新的皮肤癌。抑制50%的新皮肤 巨蟹座是意料之中的。听力将在临床上和由 听力图。将测量皮肤多胺水平和TPA对ODC的诱导 在所有随机受试者的研究开始时，随机抽样60人 受试者在2、3和4岁时在每只手臂上，在受试者的正常皮肤上 患上皮肤癌。这项研究将是对阿司匹林疗效的关键试验 DFMO及其相关的中间生物标志物ODC和多胺 级别，

DESCRIPTION: (Applicant's Description) Approximately 800,000 new skin cancers occur in the U.S. annually that represent a major economic burden to our health care system. Skin cancers have been shown to be related to UV light exposure. Of the key biochemical changes that occur, polyamine biosynthesis is consistently associated with tumor promotion. Interference with polyamine biosynthesis by inhibiting ornithine decarboxylase (ODC) enzyme with difluoromethylornithine (DFMO) reduces skin cancer formation. DFMO has been shown to inhibit ODC induced by phorbol esters applied to human skin. The proposal is designed as a phase 3 study of DFMO. The first step will be a 4 week placebo run-in study in 334 subjects to assess compliance and eliminate noncompliers (estimated at 15%). The second step is a placebo-controlled, double-blinded randomized study of DFMO in 284 (est.) subjects with a history of basal or squamous cell skin cancer. Subjects will be randomized to placebo or DFMO for an average of 4 years (range 3-5 years). Over the treatment period, about 40% of subjects will be expected to develop new skin cancers. Inhibition of 50% of all new skin cancers is anticipated. Hearing will be monitored clinically and by audiogram. Skin polyamine levels and ODC induction by TPA will be measured at start of study in all randomized subjects, in random samples of 60 subjects on each arm at 2, 3 and 4 years, and in normal skin of subjects who develop skin cancers. This study will be a pivotal trial of the efficacy of DFMO and the associated intermediary biologic markers, ODC and polyamine levels,