PHASE 2B DFMO CHEMOPREVENTION OF SKIN CANCERS IN ORGAN TRANSPLANT RECIPIENTS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。皮肤癌是美国最常见的恶性肿瘤。虽然大多数非黑色素瘤皮肤癌可以成功治疗，但在某些人群中，病例数量的增加和恶性肿瘤毒性的增加使其成为一个重大的社会风险。基于发病率和毒性的风险增加人群的一个例子是器官移植受者（OTR），由于移植物存活率和移植物受者数量的增加，器官移植受者在我们的人口中占越来越大的比例。在大多数系列中，移植后20年，OTR的皮肤癌发病率为50%。二氟甲基鸟氨酸（DFMO）是ODC的特异性抑制剂。我们建议在皮肤癌高风险的OTR患者中进行一项2b期随机研究，每天0.5g DFMO与安慰剂对比，为期一年。主要终点是皮肤样本中tpa诱导的ODC活性降低50%以上，持续一年。次要终点是皮肤腐胺减少50%，皮肤病变（光化性角化病和癌）发展减少一年。其他参数包括：毒性评估，包括耳毒性的音频图、移植物状态、依从性、DFMO和免疫抑制剂水平。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. [from CRISP website (edited)] Skin cancer is the most common malignancy encountered in the US. While most occurrences of non-melanoma skin cancer can be successfully treated, the growing number of cases and the increased virulence of the malignancy in certain populations make it a significant societal risk. An example of a population at increased risk based on incidence and virulence is organ transplant recipients (OTR), a growing subset of our population due to increased graft survival and numbers of graft recipients. In most series, the incidence of skin cancers in OTR has been > 50% by 20 years post-graft. Difluoromethylornithine (DFMO) is a specific inhibitor of ODC. We propose to perform a phase 2b randomized study of 0.5g/day of DFMO versus placebo for one year in OTR at high risk for skin cancer. The primary endpoint would be a greater than 50% reduction in TPA-induced ODC activity in skin samples for one year. Secondary endpoints will be a 50% decrease in skin putrescine and decreased development of skin lesions (actinic keratoses and carcinomas) for one year. Additional parameters include: toxicity assessment including audio grams for ototoxicity, graft status, compliance, and DFMO and immunosuppressant levels.