Long-term Exposure to Circulating Platinum is Associated with Late Effects of Treatment in Testicular Cancer Survivors
A partir d'échantillons de sérum et d'urine prélevés sur des patients ayant été traités à l'aide d'une chimiothérapie à base de cisplatine pour un cancer du testicule (durée de suivi : entre 1 et 13 ans), cette étude évalue la relation entre les niveaux de platine dans la circulation sanguine et les effets indésirables à long terme
Background :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. Patients and methods : 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. Results : 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. Conclusions : 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.