CHEMOPREVENTION OF SECOND PRIMARY TUMORS WITH 13-CIS RETINOIC ACID

用 13-顺式视黄酸化学预防第二原发肿瘤

• 批准号: 6102603
• 负责人: Waun Ki Hong
• 金额: $ 24.59万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6102603
• 关键词: 13 cis retinoate; cancer prevention; carcinogenesis inhibitor; chemoprevention; clinical research; clinical trials; dosage; drug adverse effect; drug screening /evaluation; head /neck neoplasm; human subject; human therapy evaluation; longitudinal human study; multiple primary neoplasia; neoplasm /cancer relapse /recurrence; nutrition related tag; preneoplastic state; squamous cell carcinoma; statistics /biometry; therapy compliance

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.

头颈癌早期阶段的治疗变得更加重要 成功的;然而，第二原发肿瘤（SPT）的发展 初始疾病治疗后存活的患者正在变得 越来越普遍。 SPT 的发生率每年为 3% 至 4% 之前接受过早期（I、II）期肿瘤治疗的患者。 呼吸消化道区域 SPT 的发展可能是由于 外源性致癌因素影响的“现场癌化” 整个呼吸消化道。 众所周知，类维生素A和 类胡萝卜素可以抑制和逆转致癌物诱发的癌前病变 上皮器官培养中的病变并可以抑制癌症 致癌物治疗动物的发育。 为了减少发展 我们开发并实施了使用化学预防方法的 SPT 13-顺式视黄酸的对照、双盲、随机试验 (13-cRA) 每天 50-100 mg/m2 与接受安慰剂治疗的患者相比 头颈部鳞状细胞癌。 共有103名患者接受治疗 参加了这项研究。 中位随访 32 个月后，13-cRA 治疗显着降低了第二原发性疾病的发生率 肿瘤（4% [2/49] vs. 24% [12/51]，p = 0.005）并且显着 增加了第二次原发发生的时间 (p=0.007)，从而产生 安慰剂：类维生素A相对危险度为5.59。主要问题 本研究中遇到的问题是高剂量 13-cRA 的毒性。 基于 根据这一经验，我们现在提出一项使用长期治疗的研究 低剂量 13-cRA 预防早期头部患者的 SPT 和颈部癌症。 这是一项随机、双盲、安慰剂对照的研究 13-cRA 30 mg 的研究。邮政信箱第一年每日一次，然后 15 毫克。 邮政信箱第二年和第三年每天。 共有1080名符合资格 将招募患者。 该项目的具体目标是：a) 测试低剂量 13-cRA 长期治疗减少的功效 头部和头部已治愈的患者的第二原发肿瘤（SPT） 手术和/或放射治疗导致的颈部癌症； b) 评估 低剂量 13-cRA 给药的定性和定量毒性 日常的。 该项目的总体目标是确定低剂量是否 长期治疗的13-cRA将是一种有用的化学预防剂 用于呼吸消化道上皮癌。