title: Tacrolimus and the risk of solid cancers after liver transplant: a dose effect relationship.
abstract: Although increased rates of solid organ cancers have been reported following liver transplantation (LT), the impact of quantitative exposure to calcineurin inhibitors (CNI) remains unclear. We have therefore probed the relationship between the development of solid organ cancers following LT and the level of CNI exposure. This prospective single-center study was conducted between 1995 and 2008 and is based on 247 tacrolimus-treated liver transplant recipients who survived at least 1 year following surgery. The incidence of cancer was recorded, and the mean blood concentration of tacrolimus (TC) was determined at 1 and 3 years following LT. The study results indicate that 43 (17.4%) patients developed de novo solid cancers. Mean TC during the first year after LT was significantly higher in patients who developed solid organ tumors (10.3 ± 2.1 vs. 7.9 ± 1.9 ng/mL, p < 0.0001). Independent risks factors in multivariate analysis were tobacco consumption before LT (OR = 5.42; 95% CI [1.93-15.2], p = 0.0014) and mean annual TC during the first year after LT (p < 0.0001; OR = 2.01; 95% CI [1.57-2.59], p < 0.0001). Similar effects were observed in 216 patients who received tacrolimus continuously for ≥3 years. It appears therefore that CNI should be used with caution after LT, and that new immunosuppressive therapies could deliver significant clinical benefits in this regard.
authors: Liver Transplantation Unit, Digestive Department, Saint Eloi University Hospital, University of Montpellier I, Montpellier, France.
authors: C
authors: C
authors: Carenco
authors: E
authors: E
authors: Assenat
authors: S
authors: S
authors: Faure
authors: Y
authors: Y
authors: Duny
authors: G
authors: G
authors: Danan
authors: M
authors: M
authors: Bismuth
authors: A
authors: A
authors: Herrero
authors: B
authors: B
authors: Jung
authors: J
authors: J
authors: Ursic-Bedoya
authors: S
authors: S
authors: Jaber
authors: D
authors: D
authors: Larrey
authors: F
authors: F
authors: Navarro
authors: G-P
authors: GP
authors: Pageaux
mesh_terms: D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D016559:Tacrolimus / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus
keywords: clinical research/practice; liver disease; liver transplantation: auxiliary; organ transplantation in general