HOBOKEN, NJ -- June 24, 2010 -- A study published in the July issue of [Liver Transplantation shows that cyclosporine treatment is a significant risk factor for the development of de novo cancer in liver transplant recipients.
Several studies have yielded conflicting results about the incidence of de novo cancer between cyclosporine-based and tacrolimus-based regimens. Elucidating the role of different calcineurin inhibitor (CNI) regimens in the occurrence of de novo cancer after liver transplant was the goal of this study.
Herold Metselaar, MD, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands, and colleagues performed retrospective analyses in 385 liver transplant recipients who underwent surgery between 1986 and 2007.
They analysed data included age of recipient at time of transplantation, gender of recipient, primary liver transplant indication, type of primary immunosuppressive therapy, de novo malignancy post transplantation, interval from liver transplant to diagnosis of malignancy, interval from liver transplant or diagnosis of cancer to death, and interval from liver transplant to diagnosis of the first acute rejection.
All patients were followed until December 2008. The primary endpoint was de novo malignancy, which was defined as the development of cancer other than recurrent primary liver cancer. Of the 385 study participants, 50 (13.0%) patients developed at least 1 de novo cancer.
The researchers observed that cyclosporine, in comparison with tacrolimus, is the most important risk factor for de novo malignancy after liver transplant.
This higher cancer risk was not, however, found in all cyclosporine treated patients, but cyclosporine specifically enhanced development of de novo cancer in patients transplanted in more recent years (2005-2007), and in younger patients (age, <50 y). In addition, cyclosporine treatment particularly resulted in more aggressive types of cancer compared with tacrolimus, with a 1-year survival rate of <30%.
The reason for the increased cancer rates among cyclosporine recipients is believed to be the fact that from January 2005, cyclosporine dosing based on the conventional C0 level monitoring was replaced by dosing based on C2 level monitoring in all liver transplant recipients. As this was the only major change in the cyclosporine treatment in the recent study period, the team concluded that the C2 monitoring strategy was the reason for the increased early de novo cancer risk.
"Strikingly, cyclosporine treated patients transplanted from 2005 on showed a 9.9-fold higher de novo cancer risk in the early phase after liver transplant compared with patients treated with tacrolimus, said Dr. Metselaar. "These data indicate that only the specific cyclosporine treatment used in recent years was associated with a higher risk for early development of de novo cancer."
"We also observed that, compared with tacrolimus-treated patients, cyclosporine-treated patients had a 2.5-times higher risk to develop more aggressive cancer types that do not belong to the non-melanoma skin cancer and post-transplant lymphoproliferative disorder categories, indicating that cyclosporine is not only associated with a higher early de novo cancer risk, but also with cancer types having a worse prognosis," he added.
http://www.docguide.com/news/content.nsf/news/852576140048867C8525774C007A0833
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