CHEMOPREVENTION OF SKIN CANCER: DIFLUOROMETHYLORNITHINE (DFMO) PHASE

这项研究是一项有效的III期试验，旨在使用α-二氟甲基鸟氨酸（DFMO）预防皮肤癌。 DFMO是一种化学预防剂，可抑制许多动物上皮癌和皮肤癌的促进和早期进展。 然而，DFMO尚未进行关键对照III期试验。 威斯康星州大学的研究人员先前的研究表明，DFMO可以安全地给予人类受试者，并且它抑制由佛波酯12-O-十四烷酰基佛波醇-13-乙酸酯（TPA）体外诱导的皮肤鸟氨酸脱羧酶（ODC）。我们的主要假设是：与安慰剂对照组相比，既往有一种或多种皮肤癌病史的受试者服用DFMO平均4年，新发皮肤癌的发生率是否会降低？我们的次要假设是：TPA诱导的ODC抑制是否可以作为DFMO作为化学预防剂的中间标志物？ DFMO治疗受试者皮肤中多胺水平的抑制是否可作为DFMO作为化学预防剂的中间标志物？ 在3-5年的治疗期间，DFMO给药是否可以接受？

This study is an efficient Phase III trial designed to prevent skin cancers using a-difluoromethylornithine (DFMO). DFMO is a chemopreventive agent that inhibits the promotion and early progression of many animal epithelial and skin cancers. However, DFMO has not been subjected to a pivotal controlled Phase III trial. Prior studies by University of Wisconsin investigators have shown that DFMO can be safely given to human subjects and that it inhibits skin ornithine decarboxylase (ODC), induced in vitro by the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA). Our primary hypothesis is: Will subjects with a prior history of one or more skin cancers taking DFMO for average of four years have a decrease in the rate of new skin cancers as compared to placebo controls? Our secondary hypotheses are: Will TPA-induced ODC inhibition be validated as an intermediary marker for DFMO as a chemoprevention agent? Will inhibition of polyamine levels in the skin of subjects on DFMO be validated as an intermediary marker for DFMO as a chemoprevention agent? Will DFMO administration be acceptable over the 3-5 years of treatment?