The success of cisplatin-based chemotherapy for testicular cancer comes at the price of long-term and late effects related to healthy tissue damage. We assessed and modelled serum platinum (Pt) decay after chemotherapy and determined relationships between long-term circulating Pt levels and known late effects.
In 99 testicular cancer survivors, treated with cisplatin-based chemotherapy, serum and 24-hour urine samples were collected during follow-up (1-13 years after treatment). To build a population pharmacokinetic model, measured Pt data were simultaneously analysed, together with cisplatin dose, age, weight and height using NONMEM software. Based on this model, area under the curve between 1 and 3 years after treatment (Pt AUC 1-3 years) was calculated for each patient. Predicted long-term Pt exposure was related to renal function and to late effects of treatment assessed median 9 (3-15) years after chemotherapy.
Decay of Pt was best described by a two-compartment model. Mean terminal T1/2 was 3. 7 (range 2. 5 - 5. 2) years. Pt AUC 1-3 years correlated with cumulative cisplatin dose, creatinine clearance before and 1 year after treatment. Patients with paraesthesia had higher Pt AUC 1-3 years (30. 9 vs 27. 0 µg/L*month) compared to patients without paraesthesia (P=0. 021). Patients with hypogonadism, elevated LDL-cholesterol levels or hypertension also had higher Pt AUC 1-3 years.
Renal function before and after cisplatin treatment is an important determinant of long-term Pt exposure. Known long-term effects of testicular cancer treatment such as paraesthesia, hypogonadism, hypercholesterolaemia, and hypertension are associated with long-term circulating Pt exposure.
Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. 2015 Sep 07 [Epub ahead of print]
H Boer, J H Proost, J Nuver, S Bunskoek, J Q Gietema, B M Geubels, R Altena, N Zwart, S F Oosting, J M Vonk, J D Lefrandt, D R A Uges, C Meijer, E G E de Vries, J A Gietema
Department of Medical Oncology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands. , Department of Hospital Pharmacy, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands. , Department of Medical Oncology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands. , Department of Medical Oncology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands. , Department of Medical Oncology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands. , Department of Medical Oncology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands. , Department of Medical Oncology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands. , Department of Medical Oncology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands. , Department of Medical Oncology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands. , Department of Epidemiology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands. , Department of Vascular Medicine, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands. , Department of Hospital Pharmacy, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands. , Department of Medical Oncology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands. , Department of Medical Oncology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands. , Department of Medical Oncology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands.