title: Two-year incidence of malignancy in sirolimus-treated renal transplant recipients: results from five multicenter studies.
abstract: We examined the rates of malignancy at 2 yr after transplantation in renal allograft patients receiving sirolimus (SRL) in continuous combination with cyclosporine (CsA), SRL as base therapy or SRL maintenance therapy after early withdrawal of CsA. A total of 1295 patients were enrolled in two double-blind studies comparing SRL with azathioprine (AZA) or placebo administered in continuous regimens with CsA. In two other trials (n = 161), SRL given as base therapy was compared with CsA. In the fifth trial, patients were randomly assigned at 3 months to either remain on CsA + SRL therapy (n = 215) or to have CsA eliminated with SRL being continued in concentration-controlled doses (n = 215). At 2 yr after transplantation, patients receiving SRL in continuous combination with CsA had a significantly lower incidence of skin cancer compared with patients receiving placebo. Patients receiving SRL as base therapy had no malignancies compared with a 5% incidence in those receiving CsA. The incidence of malignancy was significantly lower in patients receiving concentration-controlled SRL with elimination of CsA compared with those who remained on CsA + SRL. Based on the currently available data, patients receiving SRL-based therapy without CsA or SRL maintenance therapy after early CsA withdrawal have lower rates of malignancy in the first 2 yr after renal transplantation. SRL immunotherapy may be beneficial in protecting renal transplant patients from skin cancer even when given in combination with CsA.
authors.affiliation: Renal Unit, Queen Elizabeth Hospital, Woodville, South Australia, Australia. tmathew@bigpond.net.au
authors.forename: Timothy
authors.initials: T
authors.lastname: Mathew
authors.forename: Henri
authors.initials: H
authors.lastname: Kreis
authors.forename: Peter
authors.initials: P
authors.lastname: Friend
mesh_terms: D018890:Chemoprevention; D016572:Cyclosporine / Q000009:adverse effects; D004359:Drug Therapy, Combination; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015994:Incidence; D016030:Kidney Transplantation / Q000276:immunology; D015337:Multicenter Studies as Topic; D009369:Neoplasms / Q000139:chemically induced* / Q000276:immunology / Q000517:prevention & control; D016609:Neoplasms, Second Primary / Q000139:chemically induced / Q000453:epidemiology* / Q000276:immunology / Q000517:prevention & control; D012189:Retrospective Studies; D020123:Sirolimus / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000139:chemically induced / Q000276:immunology
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D020123:Sirolimus