BREAST CANCER CHEMOPREVENTION --SYNTHETIC RETINOID HPR

这项研究的主要目的是评估 合成维甲酸4-HPR(N-(4-羟苯基)维甲酰胺)预防 乳腺癌。4-羟丙酸(芬维替尼)是在强生公司合成的。 约翰逊实验室在60年代末，后来被证明 对不同化学诱导性乳腺癌的抑制作用 实验动物。芬雷替尼已被证明有一种 对大鼠乳腺上皮细胞增殖的抑制作用及其协同作用 增强对卵巢切除所致癌变的抑制作用 他莫昔芬。此外，4-HPR导致了对大鼠的毒性研究 毒性比视黄酸酯和维甲酸低；既不会致突变 在小鼠身上以低于100倍的剂量给药不会致癌 建议用于人类的剂量。由于它特殊地集中在 乳腺和脂肪(在人类中也存在)，4-hpr在这里被提出。 作为乳腺癌化学预防研究的首选药物。 这项研究的设计是每天口服200毫克，为期五年 4-HPR(每个月底有三天禁药假期)的阶段 I-II级乳腺癌患者年龄在33-68岁之间。这一干预 计划是随机分配的，而不是在一个 3,500-5,000名受试者，取决于视黄醇的生物活性。 这项研究的主要终点是发病率的可能下降 对侧乳房的新的初级乳房。本地、地区和远程 疾病的复发以及其他器官的新的原发 乳房也将被记录和分析。目前尚无安慰剂可用于 控制臂作为大量数据已经在急性和非急性情况下可用 非维甲酸的慢性毒性：此外，伦理考虑也是如此 由于试验时间太长，不建议这样做。然而，该协议 预见对所有乳房X光检查的盲目、公正的审查；细胞学和 所有活检的肿块的组织学检查也是由 不知道正在接受治疗的病人和那些 谁不是。 在4-HPR臂中有1.160例，在控制臂中有1,148例。在同一天， 超过50名患者已经完成了为期五年的干预。 要求提供资金以完成应计和继续后续行动。

The main aim of this study is to evaluate the effectiveness of the synthetic retinoid 4-HPR (N-(4-hydroxyphenyl)retinamide) in preventing breast cancer. 4-HPR (fenretinide) was synthetized at the Johnson & Johnson Laboratories in the late Sixties and subsequently proven to be effective in inhibiting chemically induced mammary carcinomas in different experimental animals. Fenretinide has been shown to have an antiproliferative effect on rat mammary epithelium and to synergistically enhance the inhibition of carcinogenesis resulting from ovariectomy and tamoxifen. Additionally, 4-HPR resulted in toxicity studies in rats to be less toxic than retinyl esters and retinoic acid; it is neither mutagenic nor carcinogenic when given in mice at doses below one hundred times the dosage proposed for humans. Due to its peculiar concentration in the mammary gland and fat (also demonstrated in humans), 4-HPR is here proposed as the agent of choice for a breast cancer chemoprevention study. The design of the study is to orally administer for five years 200 mg daily of 4-HPR (with a three-day drug holiday at the end of each month) to stage I-II breast cancer patients between 33-68 years of age. This intervention schedule is to be randomly assigned versus no treatment in a population of 3,500-5,000 subjects, depending on the biological activity of the retinoid. The principal endpoint of the study is the possible decrease of incidence of new primaries in the contralateral breast. Local, regional and distant recurrences of the disease as well as new primaries in organs other than the breast will also be recorded and analyzed. No placebo is foreseen for the control arm as extensive data are already available on both acute and chronic toxicity of fenretinide: moreover, ethical considerations, too, do not recommend it due to the length of the trial. However, the protocol foresees a blind, unbiased review of all mammograms; cy- tological and histological examinations of all biopsied lumps are also performed by pathologists who do not know the patients who are being treated and those who are not. 1.160 in the 4-HPR arm and 1,148 in the control arm. At the same date, more than 50 patients had already completed the five-year intervention. Funding is requested to complete accrual and to continue the follow-up.