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

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 [from CRISP网站（编辑）] 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，但病例数量的增加和某些人群中恶性肿瘤毒力的增加使其成为一个重大的社会风险。基于发病率和毒力的风险增加的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受者数量的增加，我们的人群中的一个不断增长的子集。在大多数系列中，移植后20年OTR中皮肤癌的发病率> 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危OTR患者中进行一项为期一年的2b期DFMO与安慰剂0.5g/天的随机研究。主要终点将是一年内皮肤样本中TPA诱导的ODC活性降低50%以上。次要终点将是皮肤腐胺减少50%和皮肤病变（光化性角化病和癌）发展减少1年。其他参数包括：毒性评估，包括耳毒性、移植物状态、依从性和DFMO和免疫抑制剂水平的音频图。

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.