Effect of pravastatin on survival in patients with advanced hepatocellularcarcinoma. A randomized controlled trial

Chemotherapy is not effective for hepatocellular carcinoma (HCC). HMG-CoA r edutase inhibitors have cytostatic activity for cancer cells, but their cli nical usefulness is unknown. To investigate whether pravastatin, a potent H MG-CoA reductase inhibitor, prolongs survival in patients with advanced HCC , this randomized controlled trial was conducted between February 1990 and February 1998 at Osaka University Hospital. 91 consecutive patients <71 yea rs old (mean age 62) with unresectable HCC were enroled in this study, 8 pa tients were withdrawn because or progressive liver dysfunction; 83 patients were randomized to standard treatment with or without pravastatin. All pat ients underwent transcatheter arterial embolization (TAE) followed by oral 5-FU 200 mg(-1) d for 2 months. Patients were then randomly assigned to con trol (n = 42) and pravastatin (n = 41) groups. Pravastatin was administered at a daily dose of 40 mg. The effect of pravastatin an tumour growth was a ssessed by ultrasonography. Primary endpoint was death due to progression o f HCC. The duration of pravastatin administration was 16.5 +/- 9.8 months ( mean +/- SD). No patients in either group were lost to follow-up. Median su rvival was 18 months in the pravastatin group versus 9 months in controls ( P = 0.006). The Cox proportional hazards model showed that pravastatin was a significant factor contributing to survival. Pravastatin prolonged the su rvival of patients with advanced HCC, suggesting its value for adjuvant tre atment. (C) 2001 Cancer Research Campaign.