Switch to a sirolimus-based immunosuppression in long-term renal transplant recipients: reduced rate of (pre-)malignancies and nonmelanoma skin cancer in a prospective, randomized, assessor-blinded, controlled clinical trial

Am J Transplant. 2010 Jun;10(6):1385-93. doi: 10.1111/j.1600-6143.2009.02997.x. Epub 2010 Feb 1.

Abstract

Renal transplant recipients (RTR) have a 50-200-fold higher risk for nonmelanoma-skin cancer (NMSC) causing high rates of morbidity and sometimes mortality. Cohort-studies gave evidence that a sirolimus-based immunosuppression may inhibit skin tumor growth. This single-center, prospective, assessor-blinded, randomized trial investigated if switching to sirolimus treatment inhibits the progression of premalignancies and moreover how many new NMSC occur compared to continuation of the original immunosuppressive therapy. Forty-four RTR (mean age 59.9 years, mean duration of immunosuppression 229.5 months) with skin lesions were randomized to sirolimus or continuation of their original immunosuppression. Blinded dermatological assessment at month 6 and 12 by the same dermatologist evaluated the clinical change compared to baseline. Biopsy was performed in suspected malignancy. Already the 6-month-assessment showed significant superiority of sirolimus-therapy: a stop of progression, even regression of preexisting premalignancies (p < 0.0005). This effect was increased at month 12 (p < 0.0001). Nine patients developed histologically confirmed NMSC: one in the sirolimus group, eight in the control group, p = 0.0176. Sirolimus-based immunosuppression in RTR, even when established many years after transplantation, can delay the development of premalignancies, induce regression of preexisting lesions and decelerate the incidence of new NMSC.

MeSH terms

  • Aged
  • Carcinoma, Basal Cell / epidemiology
  • Carcinoma, Basal Cell / etiology
  • Carcinoma, Squamous Cell / epidemiology
  • Carcinoma, Squamous Cell / etiology
  • Female
  • Humans
  • Immune Tolerance
  • Immunosuppression / adverse effects
  • Immunosuppressive Agents / administration & dosage*
  • Kidney Transplantation*
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Precancerous Conditions / epidemiology
  • Precancerous Conditions / etiology
  • Prospective Studies
  • Sirolimus / administration & dosage*
  • Sirolimus / adverse effects
  • Skin Neoplasms / epidemiology*
  • Skin Neoplasms / etiology

Substances

  • Immunosuppressive Agents
  • Sirolimus