Kidney Transplant Recipients Switching to Sirolimus Had Lower Risk of Secondary Squamous Cell Carcinomas

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Kidney transplant recipients with at least one previous cutaneous squamous cell carcinoma decreased their risk of developing new cutaneous squamous cell carcinomas by switching from calcineurin inhibitors (cyclosporine or tacrolimus) to sirolimus (Rapamune) in a multicenter phase III study. New squamous cell carcinomas developed in 14 of the 64 patients (22%) randomly assigned to receive sirolimus and 22 of the 56 patients (39%) who maintained their initial treatment with calcineurin inhibitors. The median time to onset was 15 months in the sirolimus group vs 7 months in the calcineurin group (P = .02)

“Several studies have shown that after a first cutaneous squamous-cell carcinoma, multiple subsequent skin cancers develop in 60% to 80% of kidney-transplant recipients within 3 years. Transplant recipients share common risk factors with the nonimmunosuppressed population, but the specific tumor burden of such patients is linked to the immunosuppressive medications used,” the authors of the Efficacy of Rapamycin in Secondary Prevention of Skin Cancers in Kidney Transplant Recipients (TUMORAPA) study noted in the introduction to their report published in The New England Journal of Medicine.

“We speculate that there may be a specific antineoplastic activity of sirolimus that explains the decrease in new skin cancers rather than a lower amount of immunosuppression,” they added after reporting their results.

Risks and Benefits

There were many more serious adverse events in the sirolimus group—60 compared to 14 in the calcineurin group. “Almost all sirolimus-treated patients had at least one adverse event that was considered to be related to the study drug,” the researchers stated. “Although serious adverse events were significantly more frequent (0.94 per patient) in the sirolimus group than in the calcineurin-inhibitor group (0.25 per patient), the number of cutaneous squamous cell carcinomas was lower by a factor of 3.4,” the investigators noted.

“The benefit–risk ratio appeared to increase with lower doses of sirolimus (as compared with higher doses) and with progressive conversion from calcineurin inhibitors to sirolimus (as compared with rapid conversion),” the authors added. “This apparent antitumoral effect was more pronounced when sirolimus was introduced after the first occurrence of a cutaneous squamous-cell carcinoma, as compared with introduction after the occurrence of multiple cutaneous squamous-cell carcinomas.” ■

Euvrard S, et al: N Engl J Med 367:329-339, 2012.




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