OLTIPRAZ CHEMOPREVENTION TRIAL IN QIDONG, JIANGSU PROVINCE, PEOPLES-REPUBLIC-OF-CHINA

Oltipraz has been used clinically in many regions of the world as an a ntischistosomal agent and is an effective inhibitor of aflatoxin hepat ocarcinogenesis in rats. This chemopreventive action of oltipraz resul ts primarily from an altered balance in aflatoxin metabolic activation and detoxication. In 1995, a randomized, placebo-controlled, double-b lind intervention was conducted in residents of Qidong, People's Repub lic of China, who are at high risk for exposure to aflatoxin and devel opment of hepatocellular carcinoma. The major study objectives were to define a dose and schedule for oltipraz that would reduce levels of a flatoxin biomarkers in biofluids of the participants, and to further c haracterize dose-limiting side effects. Two hundred thirty-four health y eligible individuals, including those infected with HBV, were random ized to receive either 125 mg oltipraz daily, 500 mg oltipraz weekly, or placebo. Blood and urine specimens were collected to monitor potent ial toxicities and evaluate biomarkers over the 8-week intervention an d subsequent 8-week follow-Lip periods. Overall, compliance in the int ervention was excellent; approximately 85% of the participants complet ed the study. Objective evaluation of adverse events was greatly facil itated by inclusion of a placebo arm in the study design. A syndrome i nvolving numbness, tingling, and pain in the fingertips was the only e vent that occurred more frequently among the active groups (18 and 14% of the daily 125 mg and weekly 500 mg arms, respectively) compared to placebo (3%). These symptoms were reversible and could be relieved wi th non-steroidal antiinflammatory agents. A more complete understandin g of the chemopreventive utility of oltipraz awaits completion of an a ssessment of the efficacy of oltipraz in modulating levels of aflatoxi n biomarkers. (C) 1998 Wiley-Liss, Inc.