Oltipraz chemoprevention trial in Qidong, People's Republic of China: study design and clinical outcomes.
Oltipraz chemoprevention trial in Qidong, People's Republic of China: study design and clinical outcomes.
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发表时间：
1997-04
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通讯作者：
A. Camoirano;M. Bagnasco;C. Bennicelli;C. Cartiglia;Jin-bing Wang;Bao-chu Zhang;Yuan‐rong Zhu;G. Qian;Patricia A. Egner;L. Jacobson;T. Kensler;S. Flora
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作者：
A. Camoirano;M. Bagnasco;C. Bennicelli;C. Cartiglia;Jin-bing Wang;Bao-chu Zhang;Yuan‐rong Zhu;G. Qian;Patricia A. Egner;L. Jacobson;T. Kensler;S. Flora
1995 年，来自中华人民共和国江苏省启东市的 234 名成年人被纳入一项 II 期化学预防试验并进行随访，该地区肝细胞癌是癌症死亡的主要原因，而且膳食中黄曲霉毒素的暴露也很普遍。该研究的目标是确定吡噻硫酮的剂量和时间表，以降低经验证的黄曲霉毒素生物标志物的水平，并表征剂量限制毒性。符合条件的健康个体，包括感染乙型肝炎病毒的个体，被随机分配每天服用 125 毫克吡噻硫酮、每周服用 500 毫克吡噻硫酮或安慰剂。收集血液和尿液样本以监测毒性并评估 8 周干预期和随后 8 周随访期的生物标志物。独特的试验方面包括同步随访时间表、每日观察所有药物的给药、及时的国际数据传输以及使用生物标志物作为结果。 132 名参与者不间断地服药，大约 77% 提供了所有 9 个尿液样本，78% 提供了所有 7 个血液样本。 51 名参与者 (21.8%) 报告了临床不良事件。与安慰剂组 (2.5%) 相比，治疗开始后不久出现的肢体综合征是活性治疗组中唯一发生频率更高 (P = 0.002) 的事件（每日 125 毫克组和每周 500 毫克组分别为 18.4% 和 14.1%）。吡噻硫酮组在症状类型或严重程度方面没有差异，并且没有迹象表明少数感染乙型肝炎病毒的参与者出现药物不耐受加剧。对严格随访计划的良好依从性表明，可以在此类人群中进行具有生物标志物终点的化学预防试验。
In 1995, 234 adults from Qidong, Jiangsu Province, People's Republic of China, where hepatocellular carcinoma is the leading cause of cancer deaths and exposure to dietary aflatoxins is widespread, were enrolled and followed in a Phase II chemoprevention trial. The goals of the study were to define a dose and schedule of oltipraz for reducing levels of validated aflatoxin biomarkers and to characterize dose-limiting toxicities. Healthy eligible individuals, including those infected with hepatitis B virus, were randomized to receive either 125 mg of oltipraz daily, 500 mg of oltipraz weekly, or placebo. Blood and urine specimens were collected to monitor toxicities and evaluate biomarkers over the 8-week intervention period and subsequent 8-week follow-up period. Unique trial aspects included a synchronous follow-up schedule, daily observed administration of all medications, timely international data transference, and use of biomarkers as outcomes. One hundred thirty-two participants took their medications without interruptions, approximately 77% contributed all nine urine samples, and 78% contributed all seven blood samples. Fifty-one participants (21.8%) reported clinical adverse events. An extremity syndrome, developing soon after the start of treatment, was the only event that occurred more frequently (P = 0.002) among the active groups (18.4 and 14.1% of the daily 125 and weekly 500 mg arms, respectively) compared with placebo (2.5%). The oltipraz arms did not differ in symptom type or severity, and there were no indications of exacerbated drug intolerance among the few participants infected with hepatitis B virus. The good compliance with an intense follow-up schedule shows that chemoprevention trials with biomarker end points may be conducted in such populations.