OLTIPRAZ CHEMOPREVENTION TRIAL IN QIDONG, PEOPLES-REPUBLIC-OF-CHINA -STUDY DESIGN AND CLINICAL OUTCOMES

In 1995, 234 adults from Qidong, Jiangsu Province, People's Republic o f China, where hepatocellular carcinoma Is the leading cause of cancer deaths and exposure to dietary aflatoxins is widespread, were enrolle d and followed in a Phase II chemoprevention trial. The goals of the s tudy were to define a dose and schedule of oltipraz for reducing level s of validated aflatoxin biomarkers and to characterize dose-limiting toxicities. Healthy eligible individuals, including those infected wit h hepatitis B virus, were randomized to receive either 125 mg of oltip raz daily, 500 mg of oltipraz weekly, or placebo. Blood and urine spec imens were collected to monitor toxicities and evaluate biomarkers ove r the 8-week intervention period and subsequent 8-week follow-up perio d. Unique trial aspects included a synchronous follow-up schedule, dai ly observed administration of all medications, timely international da ta transference, and use of biomarkers as outcomes. One hundred thirty -two participants took their medications without interruptions, approx imately 77% contributed all nine urine samples, and 78% contributed al l seven blood samples. Fifty-one participants (21.8%) reported clinica l adverse events. An extremity syndrome, developing soon after the sta rt 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 w eekly 500 mg arms, respectively) compared with placebo (2.5%). The olt ipraz arms did not differ in symptom type or severity, and there were no indications of exacerbated drug intolerance among the few participa nts infected with hepatitis B virus. The good compliance with an inten se follow-up schedule shows that chemoprevention trials with biomarker end points may be conducted in such populations.