CHEMOPREVENTION OF SECOND PRIMARY TUMORS WITH 13-CIS RETINOIC ACID

头颈癌的早期治疗已经变得越来越多， 成功;然而，第二原发性肿瘤（SPT）的发展， 患者在治疗他们的初始疾病后存活， 越来越常见。在美国，每年发生3 - 4%的SPT。 既往接受过早期（I，II）肿瘤治疗的患者。 在呼吸消化道区域发生SPT可能是由于 “田间癌变”受外源致癌因素影响， 整个呼吸消化道 众所周知，类维生素A和 类胡萝卜素可抑制和逆转致癌物诱导的癌前病变 上皮器官培养物中的病变，并且可以抑制癌 在致癌物处理的动物中的发展。 减少发展 使用化学预防方法的SPT，我们开发并进行了 13-顺式维甲酸的对照、双盲、随机试验 （13-cRA）50-100 mg/m2每日一次与安慰剂相比，在接受以下治疗的患者中 头颈部鳞状细胞癌。 共有103名患者 参加了这项研究。 在 中位随访32个月，13-cRA 治疗显著降低了第二原发性 肿瘤（4% [2/49] vs. 24% [12/51]，p = 0.005）， 增加至第二次初次治疗的时间（p=0.007）， 安慰剂：维甲酸的相对危险度为5.59。的主要问题 在这项研究中遇到的是高剂量13-cRA的毒性。 基于 根据这一经验，我们现在提出了一项长期治疗的研究， 低剂量13-cRA预防头部疾病早期患者的SPT 和颈部癌症。 这是一项随机、双盲、安慰剂对照 研究13-cRA 30 mg. P.O.第一年每天一次，然后是15 mg。 P.O.每天 第二年和第三年。 共有1080名符合条件的 患者将被招募。 该项目的具体目标是： 测试低剂量13-cRA长期治疗在降低 第二原发性肿瘤（SPT）的患者已经治愈的头部和 通过手术和/或放射疗法治疗颈癌;和B）评估 低剂量13-cRA给药的定性和定量毒性 日报 本项目的总体目标是确定低剂量 13-长期治疗的cRA将是一种有用的化学预防剂 呼吸消化道上皮癌

Treatment for early stages of head and neck cancer has become more successful; however, the development of second primary tumors (SPTs) in patients surviving after treatment of their initial disease is becoming increasingly common. SPTs occur at a rate of 3 to 4% per year in patients who were previously treated for early stage (I, II) tumors. The development of SPTs in the aerodigestive tract region may be due to "field cancerization" by exogenous carcinogenic factors which affect the entire aerodigestive tract. It is well established that Retinoids and Carotenoids can inhibit and reverse carcinogen-induced preneoplastic lesions in epithelial organ culture and can suppress carcinoma development in carcinogen-treated animals. To decrease development of SPTs using the chemopreventive approach, we developed and conducted a controlled, double-blind, randomized trial of 13-cis retinoic acid (13-cRA) 50-100 mg/m2 daily vs. placebo in patients who were treated for squamous carcinoma of the head and neck. A total of 103 patients were enrolled in this study. At a median follow-up of 32 months, 13-cRA treatment had significantly reduced the incidence of second primary tumors (4% [2/49] vs. 24% [12/51], p = 0.005) and significantly increased the time to occurrence of a second primary (p=0.007), to yield a placebo: retinoid relative hazard of 5.59. The major problem encountered in this study was toxicity from high-dose 13-cRA. Based on this experience, we now propose a study using long-term treatment with low-dose 13-cRA to prevent SPTs in patients with early stages of head and neck cancer. This is a randomized, double-blind, placebo-controlled study of 13-cRA 30 mg. p.o. daily for the first year and then 15 mg. p.o. daily for the second and third years. A total of 1080 eligible patients will be recruited. Specific aims of this project are: a) to test the efficacy of low-dose 13-cRA for long-term treatment in reducing second primary tumors (SPTs) in patients who have been cured of head and neck cancer by surgery and/or radiotherapy; and b) to evaluate the qualitative and quantitative toxicity of low-dose 13-cRA administered daily. The overall objective of this project is to establish whether low-dose 13-cRA for long-term treatment will be a useful chemopreventive agent for aerodigestive tract epithelial cancer.