Multicentre international liver tumour study protocol of the case-control study on hepatocellular cancer.

Toxicological evidence has recently shown that cyproterone acetate (CPA) is associated with increased adduct formation in liver cell cultures that was interpreted as a possible sign for genotoxicity. Likewise, a few spontaneous reports of liver cancer associated to CPA were published. This led to an alert announced by the German Drug Regulators. One reason to design a case-control study on hepatocellular cancer (HCC) and oral contraceptives (OC's) use (and specific subtypes such as CPA-containing ones) was that other clinical or pharmacoepidemiological studies were not available which dealt with this suspicion. This idea got support from the fact that most of the earlier case-control studies on HCC and OC were small, did not sufficiently control for confounding by: hepatitis B and C, exposure at work, use of other potentially hepatotoxic drugs and also did not distinguish between different types of OC's. Objectives, hypotheses, methods used and subjects studied are described in this paper. The study began in six countries (Germany, United Kingdom, France, Italy, Spain, Greece) on 1 July 1994. It will be finished by the end of June 1996, and first results can be expected by the end of 1996 or early 1997.