Pharmacokinetics of trabectedin on hemodialysis: an application for the management of cancer patients with end-stage renal disease.

PURPOSE: The pharmacokinetics of trabectedin has never been reported in patients with impaired renal function or in patients on hemodialysis. METHODS: We examined trabectedin PK in a patient on hemodialysis, starting trabectedin therapy at a standard dose for recurrence of a retroperitoneal myxoid liposarcoma that had occurred under immunosuppressive drugs for kidney transplant. RESULTS: As compared with a population with normal renal function, the study patient presented a higher C (max) and AUC, with lower clearance, terminal half-life, and volume of distribution. The low dialysis clearance, accounting for a minor part of the total body clearance and the absence of detectable trabectedin in the dialysate samples, suggests that hemodialysis does not efficiently clear trabectedin. Trabectedin tolerance was good. CONCLUSIONS: This case reports for the first time the feasibility of trabectedin therapy in a hemodialyzed patient. Given the rising incidence of cancer in patients with end-stage renal disease, it is crucial to provide data that improve the management of anticancer drugs in dialyzed patients.

Fabry disease in patients with end-stage renal failure: the potential benefits of screening.

BACKGROUND/AIMS: Alpha-galactosidase A (alpha-GLA) deficiency (Fabry disease) is an X-linked lysosomal storage disorder. The associated visceral complications are progressive and multiorgan; renal involvement is common, usually leading to end-stage renal failure (ESRF). The reported benefits of specific enzyme replacement therapy (ERT) indicate the importance of screening for Fabry disease in high-risk populations, as this approach should make it possible to identify other family members with little or no clinical features of the disease, and for them to be considered for early preventive treatment. METHODS: We screened for Fabry disease in 106 patients on hemodialysis in our hospital-based hemodialysis unit. We did this by measuring alpha-GLA enzyme activity in blood leukocytes taken from each patient and we then carried out gene analysis when indicated. RESULTS: We were able to discover 1 patient with low residual alpha-GLA activity (a prevalence of 0.94%). Alpha-GLA gene analysis identified a point mutation within the coding region producing a N215S amino acid substitution in the protein. Among the relatives of this index case, molecular testing found 7 family members with the same N215S alpha-GLA mutation. Of these, 3 had reduced alpha-GLA activity and clinical features of Fabry disease, and for which ERT was subsequently given. CONCLUSION: Screening for Fabry disease is simple and although the yield is small, it is potentially significant and of possible benefit to the relatives of affected cases in this 'at-risk' ESRF population, many of who do not have a clear renal diagnosis.