Sirolimus, when used instead of calcineurin inhibitors in transplant patients, could reduce the incidence and delay the occurrence of a repeat squamous-cell cancer of the skin, according to a recent study.
Skin cancers are common in transplant patients. The chances are higher in patients who have already suffered from a skin cancer once. Skin cancers in transplant patients are due to the reduced immunity as a consequence of the medications given post-transplantation. The drugs may also bring about the pro-carcinogenic effect through other mechanisms besides reducing immunity.
AdvertisementNewer immunosuppressant drugs used in transplant patients like sirolimus and everolimus have additional anti-cancer properties. Thus, it is possible that the use of these drugs instead of the older drugs like cyclosporine and tacrolimus (which belong to the calcineurin inhibitor group) could possibly reduce the chances of skin cancer in transplant patients. A study called the Efficacy of Rapamycin in Secondary Prevention of Skin Cancers in Kidney Transplant Recipients (TUMORAPA) assessed the efficacy of sirolimus in preventing skin cancers in those kidney-transplant patients who were already on a calcineurin inhibitor and had suffered from a skin cancer of the squamous-cell type earlier.
The 120 patients included in the study were divided into 2 groups. One group of patients continued to receive calcineurin inhibitors. The second group was shifted to sirolimus. The conversion to sirolimus was either rapid i.e. the calcineurin inhibitors were discontinued within 7 days, or progressive if the conversion took longer.
Before the study, 55% patients had suffered from a single squamous-cell cancer earlier, whereas the remaining patients had suffered from more than one skin cancer.
The researchers found that patients on sirolimus were free of squamous-cell cancer for longer periods than those on calcineurin inhibitors. New squamous-cell cancers developed in 14 patients of the sirolimus group as compared to 22 patients of the calcineurin-inhibitor group. In 6 patients from the sirolimus group, the cancer developed only after sirolimus was stopped.
The anti-cancer benefits of sirolimus were usually more pronounced in those who had suffered from a single squamous-cell cancer before the study as compared to those who had already suffered multiple cancers.
The use of sirolimus was, however, associated with a higher incidence of adverse effects. These occurred in nearly all the patients taking sirolimus and were mostly seen during the first 6 months of treatment. A reduction in dose or additional medications helped to control the symptoms. Patients who underwent rapid conversions showed a higher rate of discontinuation as well as serious adverse effects as compared to those underwent progressive conversions.
The study thus indicates that replacement of calcineurin inhibitors with sirolimus not only decreases the risk of development of new squamous cell cancers of the skin, it also delays the occurrence of these lesions. However, the incidence of adverse effects was higher in the sirolimus group. Using lower doses of sirolimus and adopting progressive conversions could help to reduce the chances of adverse effects.
1. Sirolimus and Secondary Skin-Cancer Prevention in Kidney Transplantation; Sylvie Euvard et al; N Engl J Med 2012; 367:329-339