Jacobson L P, Zhang B C, Zhu Y R, Wang J B, Wu Y, Zhang Q N, Yu L Y, Qian G S, Kuang S Y, Li Y F, Fang X, Zarba A, Chen B, Enger C, Davidson N E, Gorman M B, Gordon G B, Prochaska H J, Egner P A, Groopman J D, Muñoz A, Helzlsouer K J, Kensler T W
Qidong Liver Cancer Institute, Jiangsu Province, People's Republic of China.
Cancer Epidemiol Biomarkers Prev. 1997 Apr;6(4):257-65.
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.
1995年，来自中华人民共和国江苏省启东市的234名成年人参加了一项II期化学预防试验，并对其进行随访。在启东市，肝细胞癌是癌症死亡的主要原因，膳食黄曲霉毒素暴露很普遍。该研究的目的是确定奥替普拉的剂量和给药方案，以降低经过验证的黄曲霉毒素生物标志物水平，并确定剂量限制毒性。符合条件的健康个体，包括那些感染了乙肝病毒的个体，被随机分为三组，分别每日接受125毫克奥替普拉、每周接受500毫克奥替普拉或接受安慰剂。在为期8周的干预期和随后8周的随访期内，收集血液和尿液样本以监测毒性并评估生物标志物。该试验的独特之处包括同步随访计划、所有药物每日观察给药、及时的国际数据传输以及将生物标志物用作结果指标。132名参与者不间断地服用药物，约77%的参与者提供了全部9份尿液样本，78%的参与者提供了全部7份血液样本。51名参与者（21.8%）报告了临床不良事件。一种在治疗开始后不久出现的肢体综合征是唯一在活性药物组中比安慰剂组更频繁发生的事件（P = 0.002），活性药物组中，每日服用125毫克奥替普拉组和每周服用500毫克奥替普拉组分别有18.4%和14.1%的参与者出现该症状，而安慰剂组为2.5%。奥替普拉组在症状类型或严重程度上没有差异，并且在少数感染乙肝病毒的参与者中没有出现药物不耐受加剧的迹象。对密集随访计划的良好依从性表明，以生物标志物为终点的化学预防试验可以在这类人群中进行。
