Cisplatin pharmacokinetics in a child receiving peritoneal dialysis

Division of Pediatric Nephrology, The Children's Mercy Hospital and Clinics, University of Missouri at Kansas City, Kansas City, MO, USA.
Pediatric Nephrology (Impact Factor: 2.86). 06/2010; 25(6):1185-9. DOI: 10.1007/s00467-009-1420-6
Source: PubMed


Cisplatin is a highly effective and frequently used drug in the chemotherapy of solid tumors in children, but there is currently no information to guide dosing in children requiring dialysis. Here, we present the case of a 2-year-old boy with end-stage renal disease managed with peritoneal dialysis and requiring cisplatin for a newly diagnosed hepatoblastoma. A pharmacokinetic study was performed to personalize the cisplatin dose with the goal of providing adequate cisplatin exposure and avoiding excessive exposure and toxicity. Accordingly, 25% of the standard cisplatin dose was infused intravenously over 4 h. Serial blood and peritoneal fluid samples were obtained, and free cisplatin levels were subjected to noncompartmental pharmacokinetic analysis. The disposition of free cisplatin was significantly altered as compared to that of normal children. Despite a 75% dose reduction, our patient showed a fourfold increase in free cisplatin exposure (AUC = 64.1 h mcg/mL) compared with the AUC observed in children with normal kidney (15 + or - 9 h mcg/mL) function. When a subsequent dose was decreased to 8.7% of the standard dose, the free cisplatin AUC measured 29.7 h mcg/mL and more closely approximated the exposure observed in children with normal kidney function.

10 Reads
  • [Show abstract] [Hide abstract]
    ABSTRACT: Prune belly syndrome (PBS) is a congenital anomaly characterized by the clinical triad of lax abdominal musculature, bilateral cryptorchidism, and abnormalities of the kidney and urinary tract. Previous reports of malignancy in patients with PBS have been limited to germ cell tumors. Hepatoblastoma (HBL) is the most common hepatic malignancy of childhood, affecting approximately 100 children each year in the USA. We describe a set of 4 pediatric patients with PBS and HBL. All individuals were born after 2002. These subjects lacked genetic, natal, or environmental factors known to confer risk of HBL. The occurrence of PBS and HBL in these patients constitutes a novel potential association.
    Pediatric Nephrology 08/2011; 26(8):1269-73. DOI:10.1007/s00467-011-1874-1 · 2.86 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To prove the feasibility and toxicity of platinum-based chemoradiation in a patient with recurrent cervical cancer undergoing concomitant hemodialysis. We report a patient with a renal transplant because of chronic renal failure who then underwent radical hysterectomy and lymphadenectomy due to cervical cancer FIGO stage IB1. One year after primary therapy, a 53 × 54 × 68 mm vaginal stump recurrence was treated by total translevatoric exenteration with lymphadenectomy, explantation of the transplant, and the right residual kidney. Because of microscopically involved margins, chemoradiation was recommended. Radiation was performed to the tumor region and pelvic lymph nodes up to 50.4 Gy. A boost was given to the clip-marked region to 66.6 Gy. Neurological, gastrointestinal and genitourinary toxicity was evaluated once a week, while hematological toxicity twice per week. Samples to evaluate cisplatin concentrations were taken from blood and dialysate. The patient completed chemoradiation with 5 cisplatin applications with a decreased dose (20 mg/m(2)) without any high grade toxicity. Hemodialysis was performed three times a week. Within 30 min after cisplatin application, the cisplatin serum concentration reached the highest level with 1,179.6 µg/l and showed nearly stable concentrations over 120 min. There was an accumulation of cisplatin from week 1 (100%) to week 5 of application (219%). The corresponding concentration in the dialysate also showed a rapid increase within the first hour of hemodialysis and decreased to 50% within 2 h. Cisplatin application with a modified dose (20 mg/m(2)) is feasible and safe in a patient with cervical carcinoma undergoing chemoradiation and hemodialysis.
    Strahlentherapie und Onkologie 11/2011; 187(12):831-4. DOI:10.1007/s00066-011-2281-z · 2.91 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to describe the nonlinear pharmacokinetics of total and unbound plasma cisplatin under different administered time in patients with non-small-cell lung carcinoma. Patients receiving chemotherapy with cisplatin were included in this analysis. Patients were divided into two groups depending on the administrated time of cisplatin: 6:00 (Group A) and 18:00 (Group B). The population pharmacokinetics of cisplatin was calculated using nonlinear mixed-effects modeling (NONMEM) method, and the possible influence of covariates on the population pharmacokinetics of cisplatin was also explored. The pharmacokinetics of total and unbound cisplatin could be described well by a linear two-compartment model. The mean population estimates for total and unbound drug were, respectively, 0.463 (17.0 %) and 25.4 (14.0 %) l h(-1) for clearance (CL), 24.2 (19.9 %) and 20.5 (27.1 %) l for central distribution volume (V 1), 10.2 (18.2 %) and 9.82 (28.1) l h(-1) for intercompartmental clearance (Q) and 32.0 (24.1 %) and 6.77 (25.4 %) l for peripheral compartment volume (V 2). The CL for total and unbound cisplatin was dependent on body surface area (BSA). When cisplatin was administered at 18:00, the CL was 1.38- and 1.22-fold higher than those administered at 6:00 for total and unbound cisplatin, respectively (P < 0.05). The mean parameter estimates from a nonparametric bootstrap procedure were comparable and within 5 % of the estimates from NONMEM. The results showed that circadian could influence the metabolism of cisplatin and suggested the conventional dose adjustment of cisplatin based on BSA.
    Cancer Chemotherapy and Pharmacology 09/2013; 72(5). DOI:10.1007/s00280-013-2288-5 · 2.77 Impact Factor
Show more