title: Sirolimus and secondary skin-cancer prevention in kidney transplantation.
abstract: BACKGROUND
  Transplant recipients in whom cutaneous squamous-cell carcinomas develop are at high risk for multiple subsequent skin cancers. Whether sirolimus is useful in the prevention of secondary skin cancer has not been assessed.
  
  
  METHODS
  In this multicenter trial, we randomly assigned transplant recipients who were taking calcineurin inhibitors and had at least one cutaneous squamous-cell carcinoma either to receive sirolimus as a substitute for calcineurin inhibitors (in 64 patients) or to maintain their initial treatment (in 56). The primary end point was survival free of squamous-cell carcinoma at 2 years. Secondary end points included the time until the onset of new squamous-cell carcinomas, occurrence of other skin tumors, graft function, and problems with sirolimus.
  
  
  RESULTS
  Survival free of cutaneous squamous-cell carcinoma was significantly longer in the sirolimus group than in the calcineurin-inhibitor group. Overall, new squamous-cell carcinomas developed in 14 patients (22%) in the sirolimus group (6 after withdrawal of sirolimus) and in 22 (39%) in the calcineurin-inhibitor group (median time until onset, 15 vs. 7 months; P=0.02), with a relative risk in the sirolimus group of 0.56 (95% confidence interval, 0.32 to 0.98). There were 60 serious adverse events in the sirolimus group, as compared with 14 such events in the calcineurin-inhibitor group (average, 0.938 vs. 0.250). There were twice as many serious adverse events in patients who had been converted to sirolimus with rapid protocols as in those with progressive protocols. In the sirolimus group, 23% of patients discontinued the drug because of adverse events. Graft function remained stable in the two study groups.
  
  
  CONCLUSIONS
  Switching from calcineurin inhibitors to sirolimus had an antitumoral effect among kidney-transplant recipients with previous squamous-cell carcinoma. These observations may have implications concerning immunosuppressive treatment of patients with cutaneous squamous-cell carcinomas. (Funded by Hospices Civils de Lyon and others; TUMORAPA ClinicalTrials.gov number, NCT00133887.).
authors: Department of Dermatology, Hospices Civils de Lyon, Edouard Herriot Hospital Group, Lyon, France. sylvie.euvrard@numericable.fr
authors: Sylvie
authors: S
authors: Euvrard
authors: Emmanuel
authors: E
authors: Morelon
authors: Lionel
authors: L
authors: Rostaing
authors: Eric
authors: E
authors: Goffin
authors: Anabelle
authors: A
authors: Brocard
authors: Isabelle
authors: I
authors: Tromme
authors: Nilufer
authors: N
authors: Broeders
authors: Veronique
authors: V
authors: del Marmol
authors: Valérie
authors: V
authors: Chatelet
authors: Anne
authors: A
authors: Dompmartin
authors: Michèle
authors: M
authors: Kessler
authors: Andreas L
authors: AL
authors: Serra
authors: Günther F L
authors: GF
authors: Hofbauer
authors: Claire
authors: C
authors: Pouteil-Noble
authors: Josep M
authors: JM
authors: Campistol
authors: Jean
authors: J
authors: Kanitakis
authors: Adeline S
authors: AS
authors: Roux
authors: Evelyne
authors: E
authors: Decullier
authors: Jacques
authors: J
authors: Dantal
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D065095:Calcineurin Inhibitors; D002294:Carcinoma, Squamous Cell / Q000517:prevention & control*; D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D020123:Sirolimus / Q000009:adverse effects / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000517:prevention & control*; D016559:Tacrolimus / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D065095:Calcineurin Inhibitors; D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D020123:Sirolimus; D016559:Tacrolimus