Effect of immunosuppression for primary renal disease on the risk of cancer in subsequent renal transplantation: a population-based retrospective cohort study.

BACKGROUND: To measure the risk of cancer in renal transplantation for recipients who had previously been treated with immunosuppressive agents for primary renal disease. METHODS: A retrospective population-based cohort study of 5970 renal transplant recipients in Australia registered on the Australia and New Zealand Dialysis and Transplant Registry between 1982 and 1997 and followed until 2007. Data about the incidence of a range of cancer types from this Registry were compared with cancer incidence data for the general population matched for cancer type, year of incidence, age, and gender derived from national cancer records. Outcome measures for each cancer group with or without pretransplantation immunosuppression were cancer-specific standardized incidence ratios and a multivariate hazard ratio (HR) standardized to 1. RESULTS: For those treated with pretransplantation immunosuppression, the risks for four cancer groups during renal transplantation were significantly increased: anogenital cancer (HR, 3.13; confidence interval [CI], 1.92-5.11; P<0.0001), non-Hodgkin's lymphoma (HR, 2.37; CI, 1.53-3.68; P=0.0001), breast cancer (HR, 2.52; CI, 1.13-5.61; P=0.024), and urinary tract cancer (excluding kidney) (HR, 1.84; CI, 1.13-3.01; P=0.015). However, the risks of cancer in the oral cavity and pharynx, kidney, thyroid, colon, leukemia, lung, melanoma, prostate, and stomach were not significantly increased. CONCLUSIONS: Pretransplantation immunosuppression for primary renal disease increases the risks of four cancer types in renal transplantation while sparing the others. Patients in whom this treatment is being considered should be informed of these risks.

Assessment of the bioequivalence of a generic cyclosporine A by a randomized controlled trial in stable renal recipients.

BACKGROUND: The aim of this study was to determine the bioequivalence of Cysporin, a generic cyclosporine A, compared with Neoral in stable renal transplant recipients. METHODS: Study design consisted of an open label, two-way crossover, randomized controlled trial of Cysporin versus Neoral in stable renal transplant recipients. In all, 33 patients were enrolled; 31 were randomized and 28 were evaluable. AUCs(0-12) were done on day 14 and 28; C(0) and C(2) were done on days 0, 7, 21 and 35. Dose conversion was 1:1. Outcome measures for serum cyclosporin A concentrations expressed as the mean+/-SD were AUC(0-12) (microg x hr/L), C(max) (microg/L), C(2) (microg/L), T(max) (hr) and T(1/2) (hr). Mean and 90% CI of the ratio Cysporin/Neoral of log-transformed data were calculated using a general linear model. RESULTS: The main pharmacokinetic features were: AUC(0-12): Cysporin 3495+/-1319, Neoral 3853+/-1378 (P<0.05); C(max): Cysporin 755+/-301, Neoral 881+/-368 (P<0.05); C(2): Cysporin 613+/-235, Neoral 672+/-255 (P>0.05); T(max): Cysporin 1.9+/-0.8, Neoral 1.4+/-0.6 (P<0.005); and T1/2: Cysporin 8.8+/-4.3, Neoral 8.7+/-6.2 (P>0.05). Estimated ratios of Cysporin/Neoral were: AUC 0.93 (90% CI 0.88-0.98; P<0.05); C(max) 0.88 (90% CI 0.80-0.97; P<0.05); and T(max) 1.32 (90% CI 1.14-1.53; P<0.005). CONCLUSIONS: Both the extent and rate of absorption of Cysporin are significantly less than those of Neoral. The 90% CI for the ratios of Cysporin/Neoral for AUC and C(max) lie within 0.80-1.25. Hence in this clinical context Cysporin is pharmacologically bioequivalent with Neoral. This study illustrates the importance of testing bioequivalence of generic cyclosporine A products in transplant recipients not healthy volunteers.