CHEMOPREVENTION TRIALS IN SKIN AND ORAL CANCERS

作为该计划项目的一部分，我们已经进行了临床试验 人类癌症中的维甲酸类化合物，并检测到并报告了显著的活性 真菌病和晚期皮肤鳞状/基底细胞癌。在……里面 在头颈癌中观察到了附加反应， 骨髓增生异常综合征和黑色素瘤。我们还在 癌前病变皮肤和口腔的癌前病变由于潜在的 可逆性治疗对癌症预防的意义 对于癌前病变，我们计划将目前的努力集中在这一领域。 我们将使用Beta版扩展我们先前试验的有希望的结果- 胡萝卜素用于治疗口腔白斑，作为这项研究的一部分 计划项目。此外，我们将开发和评估一个主题 不可逆α-二氟甲基鸟氨酸(DFMO)的合成 鸟氨酸脱羧酶抑制剂，在光化性I期试验中 角化病。DFMO作为一种预防制剂具有相当大的价值。 然而，对于皮肤癌的预防，局部制剂将是 对于临床研究和使用具有极大的价值，因为它将消除 以及与全身使用该化合物相关的毒性。这一阶段 I研究之后将进行随机、安慰剂对照的II期试验 比较外用DFMO和反式维甲酸(视黄酸-A)治疗这种疾病的疗效。 虽然这笔赠款中没有包括一项提案，但我们希望能够 在其他癌前病变中进行局部DFMO的未来研究 皮肤，例如发育不良的雀斑综合症。临床试验项目已经 大大提高了我们对维甲酸和维甲酸作用的认识 类胡萝卜素在癌前和肿瘤中的作用及研究现状 提案将深化和扩大这一努力，特别是在 口腔创业症。白斑研究的提出将提供依据 在这种疾病中使用β-胡萝卜素和预防头部和 颈癌。光化性角化病的研究将导致一个局部的， 因此，毒性小、易接受，制备的DFMO适合于 对这种疾病的临床研究，并可用于其他 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.