Lovastatin, an inhibitor of mevalonate synthesis, demonstrated in vitro antitumor activity against a variety of human cancer cells, especially in gastric adenocarcinoma cells at pharmacologically achievable concentrations. To determine the antitumor activity of this drug in advanced measurable gastric adenocarcinoma as well as to assess the toxicities and the pharmacokinetic features, we carried out a phase II study of high-dose lovastatin. Patients received lovastatin 35 mg/kg/day for 7 consecutive days, with ubiquinone (60 mg qid p.o.) to prevent rhabdomyolysis. The treatment was repeated every 28 days. From March 1996 to January 1997, 16 patients (median age, 57 years; range, 34-68) were entered into the study, 14 of whom were evaluated for response and toxicity. No patient achieved a response. A total of 28 cycles were administered. The median number of cycles was 2 (range, 1 to 4). Anorexia was the most common toxicity (64%), but decreased oral intake was observed only in 3 cycles. Two patients developed myalgia with elevated muscle enzyme. When used in this dosage and schedule, lovastatin does not appear to be effective for patients with advanced gastric adenocarcinoma.