CHEMOPREVENTION OF SECOND PRIMARY TUMORS WITH 13-CIS RETINOIC ACID

对早期头颈癌的治疗已变得越来越多 成功；然而，第二原发肿瘤(SPTS)的发展 在最初的疾病治疗后存活的患者正在成为 越来越普遍。年，SPT以每年3%至4%的速度发生 曾接受过早期(I、II)肿瘤治疗的患者。 SPTS在航空消化道的发展可能是由于 外源性致癌因素影响肿瘤细胞的“野战癌变” 整个空气中的消化道。众所周知，维甲酸和维甲酸 类胡萝卜素抑制和逆转致癌物诱导的癌前病变 上皮器官培养中的损伤和对肿瘤的抑制 致癌物处理动物的研究进展。减少……的发展 使用化学预防方法，我们开发和实施了 13-顺式维甲酸随机双盲对照试验 (13-CRA)每日50-100 mg/m2与安慰剂对照 头颈部的鳞状细胞癌。共有103名患者接受了治疗。 参加了这项研究。在中位32个月的随访中，13-CRA 治疗显著降低了二次初诊的发生率 肿瘤(4%[2/49]vs.24%[12/51]，p=0.005)，显著 增加了第二次初选的发生时间(p=0.007)，以产生 安慰剂：维甲酸的相对风险为5.59。主要问题是 在这项研究中遇到的是大剂量13-CRA的毒性。基于 这一经历，我们现在建议进行一项研究，使用长期治疗 小剂量13-CRA预防早期颅脑损伤患者的SPTS 和颈癌。这是一种随机、双盲、安慰剂对照的 13-CRA 30 mg.邮政总局第一年每天服用，然后是15毫克。 邮政总局第二年和第三年每天都有。共有1080名符合资格 患者将被招募。该项目的具体目标是：a) 小剂量13-CRA长期治疗减少性脑出血的疗效观察 已治愈的头颈部肿瘤患者的第二原发瘤 接受手术和/或放射治疗的宫颈癌；以及b)评估 小剂量13-CRA的定性和定量毒性 每天。 该项目的总体目标是确定低剂量 13-CRA用于长期治疗将是一种有用的化学预防药物 治疗呼吸道上皮癌。

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.