Chemoembolization Combined with Pravastatin Improves Survival in Patients with Hepatocellular Carcinoma

Abstract

Background/Aims: Pravastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, has been shown to inhibit growth and to induce apoptosis in human hepatocellular carcinoma (HCC) cells. However, the potential benefit of pravastatin in HCC patients has still not been characterized, which prompted us to test the efficacy of pravastatin in patients with advanced HCC. Methods: We investigated prospectively a cohort of 183 HCC patients who had been selected for palliative treatment by transarterial chemoembolization (TACE). Fifty-two patients received TACE combined with pravastatin (20–40 mg/day) and 131 patients received chemoembolization alone. Six independent predictors of survival according to the Vienna survival model for HCC were equally distributed in both groups. Results: During the observation period of up to 5 years, 31 (23.7%) out of 131 patients treated by TACE alone and 19 (36.5%) out of 52 patients treated by TACE and pravastatin survived. Median survival was significantly longer in HCC patients treated by TACE and pravastatin (20.9 months, 95% CI 15.5–26.3, p = 0.003) than in HCC patients treated by TACE alone (12.0 months, 95% CI 10.3–13.7). Conclusion: Combined treatment of chemoembolization and pravastatin improves survival of patients with advanced HCC in comparison to patients receiving chemoembolization alone.

Pharmacological Actions of Statins: A Critical Appraisal in the Management of Cancer

“…The authors found that 40 mg/day pravastatin significantly increased the median survival (doubled in pravastatin-treated group compared with STATINS AND CANCER: PROS AND CONS untreated group). Similar results have been reported from the analysis of a cohort of 183 patients with advanced HCC treated with palliative TACE and pravastatin (Graf et al, 2008). On the other hand, Lersch et al (2004) failed to replicate these results in HCC previously treated with octreotide for 2 months.…”

“…A significant prolonged survival has been also reported in a recent cohort study analyzing 183 patients with hepatocellular carcinoma (HCC) (Graf et al, 2008). All patients received palliative treatment with transarterial chemoembolization (TACE) and then were assigned to a treatment group (oral pravastatin at 20 -40 mg/day; n ϭ 52) or to a control group (treated with TACE alone; n ϭ 131).…”

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“…Results show a significant prolonged survival in statin-treated group [65]. Similar positive effects have been demonstrated in the report by Graf and the colleagues on the treatment of patients with hepatocellular carcinoma by transarterial chemoembolization combined with pravastatin [66]. Several epidemiologic studies also suggest a positive correlation between increased serum cholesterol content and risk for some cancer types including prostate cancer, melanoma and non-metastatic rectal cancer [15,52,[67][68][69].…”

Targeting tumor cell metabolism with statins

“…184,185 It is worth noting, however, that two of the most successful anticancer statin trials to date were conducted in hepatocellular carcinoma patients treated with pravastatin, a hydrophilic statin. 57,69 The success of a hydrophilic statin in this case may in fact be because of their hepatoselective nature. This suggests that different statins may be better suited for treating some tumors but not others and that they should be deliberately chosen based upon distinct characteristics.…”

“…Finally, randomized controlled trials have also conducted in advanced hepatocellular carcinoma patients. Patients were treated with either transcatheter arterial embolization and oral 5-flurouracil 56 or transarterial chemoembolization, 69 both in the presence or absence of statin therapy. Remarkably, statin treatment approximately doubled the survival time of these patients in both trials.…”