NEW YORK (Reuters Health) – Among patients undergoing liver transplantation for hepatocellular carcinoma, the risk of recurrence is lower when immunosuppression is based on sirolimus rather than calcineurin inhibitors, according to a recent meta-analysis.
“The improved outcomes with reduction in recurrence-related mortality in the presence of significant other poor prognostic factors … support the potential antiproliferative tumour effect of SRL (sirolimus),” the authors conclude in the current online issue of Alimentary Pharmacology and Therapeutics.
Dr. Nigel Heaton, with King’s College Hospital, London and colleagues explain that calcineurin inhibitors conventionally used for immunosuppression after liver transplantation have been implicated in promoting tumor formation.
On the other hand, sirolimus has antitumor as well as immunosuppressive effects, through inhibition of mTOR receptors. “The antitumour activity of SRL occurs at the same concentrations as the maintenance target levels in posttransplant patients,” the authors note.
To assess cancer outcomes with sirolimus-based immunosuppression following liver transplantation for HCC, the team conducted a systematic review of the literature and identified five relevant studies involving a total of 474 patients. Median follow-up ranged from 18 to 49 months. Three of the studies compared sirolimus-treated patients to those treated with a calcineurin inhibitor.
The tumor recurrence rate was lower with sirolimus (4.9%-12.9%) than with calcineurin inhibitors (17.3%-38.7%), the researchers found. Recurrence-free survival was also much better with sirolimus. For example, at 5 years, recurrence-free survival in the two groups was 79%-80% versus 54%-60%, respectively.
The odds ratio for recurrence with sirolimus versus calcineurin inhibitors was 0.30 (p
Dr. Heaton and colleagues acknowledge that the quality of all the included studies was low, and there are limitations to their analysis. Nonetheless, they conclude, “The review showed lower recurrence rate, longer recurrence-free survival and overall survival and lower recurrence-related mortality in sirolimus-treated patients in comparison with the calcineurin inhibitor-treated patients following liver transplantation for hepatocellular carcinoma.”
“However,” they add, “results from randomized studies such as the SiLVER trial would help in proving the oncological benefit of SRL post-LT (liver transplantation) for HCC and the use of SRL-based immunosuppression protocols for the future.”
