CHEMOPREVENTION TRIALS IN SKIN AND ORAL CANCERS

作为该项目的一部分，我们已经进行了临床试验， 类维生素A在人类癌症中的作用， 蕈样肉芽肿和晚期皮肤鳞状/基底癌。在 在头颈癌中也观察到了另外的反应， 骨髓增生异常综合征和黑素瘤。 我们还进行了试验， 皮肤和口腔的癌前病变。 由于潜在的 能够逆转的治疗对癌症预防的意义 癌前病变，我们计划集中我们目前的努力在这方面。 我们将扩大我们以前的试验使用beta- 胡萝卜素用于治疗口腔白斑进行了一部分，这 程序项目。 此外，我们还将开发和评估一个主题 α-二氟甲基鸟氨酸（DFMO），一种不可逆的 鸟氨酸脱羧酶抑制剂，在光化 角化病 DFMO作为预防剂具有相当大的意义。 然而，对于皮肤癌预防，局部制剂将是 临床研究和使用的巨大价值，因为它将满足需要， 以及与全身使用该化合物相关的毒性。 相位 I研究之后将进行随机、安慰剂对照II期试验 比较局部DFMO与反式维甲酸（Retin-A）在这种疾病中的作用。 虽然一个建议是不包括在这个赠款，我们希望能够 在其他癌前病变中进行局部DFMO的未来研究， 皮肤，例如发育不良痣综合征。 临床试验项目 大大增强了我们对类维生素A作用的认识， 类胡萝卜素在肿瘤前和肿瘤条件和电流 这些建议将深化和扩大特别是在下列领域努力 口腔癌前病变 白斑病的研究建议将提供基础 β-胡萝卜素在这种疾病中的应用以及预防头部和 颈癌 光化性角化病研究将导致局部， 因此，毒性更小，更容易被接受，制备的DFMO适用于 在这种疾病的临床研究，并可用于测试在其他 条件

As part of this program project, we have carried out clinical trials using retinoids in human cancers and detected and reported significant activity in mycosis fungoides and advanced squamous/basal cancer of the skin. In addition responses have been observed in head and neck cancer, myelodysplastic syndromes and melanoma. We have also conducted trials in premalignant lesions of the skin and oral cavity. Owing to the potential significance to cancer prevention of treatments capable of reversing preneoplastic lesions, we plan to focus our current efforts in this area. We will expand on the promising results of our previous trial using beta- carotene for the treatment of oral leukoplakia conducted as a part of this program project. In addition, we will develop and evaluate a topical formulation of alpha-difluoramethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, in a phase I trial in actinic keratosis. DFMO is of considerable interest as a prevention agent. However, for skin cancer prevention, a topical preparation would be of immense value for clinical study and use, since it would obviate the need for and toxicity associated with systemic use of this compound. The phase I study will be followed by a randomized, placebo-controlled phase II trial comparing topical DFMO with trans-retinoic acid (Retin-A) in this disease. Although a proposal is not included in this grant, we hope to be able to undertake future studies with topical DFMO in other premalignant lesions of the skin, e.g. dysplastic nevus syndrome. The clinical trials project has enhanced considerably our knowledge of the role of retinoids and carotenoids in preneoplastic and neoplastic conditions and the current proposal will deepen and expand that effort particularly in the area of oral preneoplasia. The leukoplakia study proposed will provide the basis for use of beta-carotene in this disease and the prevention of head and neck cancer. The actinic keratosis study will result in a topical, therefore, less toxic and more acceptable, preparation of DFMO suitable for clinical study in this disease and available for testing in other conditions.