Results, toxicity and compliance in chemoprevention trials of head and neck cancer.
Results, toxicity and compliance in chemoprevention trials of head and neck cancer.
复制标题
头颈癌化学预防试验的结果、毒性和依从性。
DOI：
10.1097/00008469-199401000-00009
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
R. Rosso
中科院分区：
文献类型：
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作者：
S. Toma;R. Palumbo;R. Rosso
多项临床试验已证明维生素 A 或其天然前体、β-胡萝卜素或其合成类似物、类维生素A 作为化学预防剂对上呼吸消化道 (UADT) 癌具有功效。特别是，13-顺式视黄酸 (cRA) 已被证明可以逆转口腔白斑并降低头颈癌患者第二原发肿瘤的发生率。由于化学预防治疗必须持续很长时间（甚至数年），并且由于接受治疗的患者表面上“健康状况良好”，因此需要仔细考虑所用药物的毒性和治疗的依从性。目前的临床研究已经评估了低剂量cRA在大量患者中的疗效，并且当cRA与重组α-干扰素2a（r-α-IFN 2a）联合使用时，其有效性的增加也为头颈部鳞状细胞癌患者带来了较高的客观缓解率。验证几种生物标志物（特别是微核）作为化学预防研究中间终点的有效性的体外和体内研究仍在继续，以便短期筛选有前景的化学预防药物用于临床试验。我们回顾了有关此事的已发表文献，特别关注类维生素A治疗和毒性/依从性相关问题，并与我们自己的经验进行比较。
Several clinical trials have demonstrated the efficacy as chemopreventive agents on upper aerodigestive tract (UADT) cancer of vitamin A or its natural precursor, beta-carotene, or its synthetic analogues, retinoids. Particularly, 13-cis-retinoic acid (cRA) has been shown to reverse oral leukoplakia and to reduce the frequency of second primary tumours in patients treated for head and neck cancer. Since chemopreventive treatments must be of very long-term duration (even years), and because of apparent 'good health' of treated patients, the toxicity of used drugs and the compliance with treatment need to be carefully considered. Current clinical research has evaluated the efficacy of low doses of cRA in larger numbers of patients, and the increased effectiveness of cRA when used in combination with recombinant alpha-interferon 2a (r-alpha-IFN 2a) has also produced high objective response rate in patients affected with squamous cell carcinoma of the head and neck. In vitro and in vivo studies to verify the validity of several biomarkers (in particular micronuclei) as intermediate end-points in chemoprevention studies are continuing, to allow the short-term screening of promising chemopreventive drugs to be used in clinical trials. The published literature on this matter is reviewed, with special attention to retinoid treatment and toxicity/compliance-related problems, and compared with our own experience.