Long-term exposure to circulating platinum is associated with late effects of treatment in testicular cancer survivors.

Abstract

BACKGROUND:

The success of cisplatin-based (Platinol, Bristol-Myers Squibb Company, New York, NY, USA) 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-h 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 the NONMEM software. Based on this model, area under the curve between 1 and 3 years after treatment (Pt AUC1-3 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 AUC1-3 years correlated with cumulative cisplatin dose, and creatinine clearance before and 1 year after treatment. Patients with paraesthesia had higher Pt AUC1-3 years (30.9 versus 27.0 µg/l month) compared with those without paraesthesia (P = 0.021). Patients with hypogonadism, elevated LDL-cholesterol levels or hypertension also had higher Pt AUC1-3 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.

• Authors: 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
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 26 Issue 11 Pg. 2305-10 (Nov 2015) ISSN: 1569-8041 [Electronic] England
• PMID: 26347114 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

Chemical References

• Platinum
• Cisplatin

Topics

• Adult
• Cisplatin (adverse effects, therapeutic use)
• Follow-Up Studies
• Humans
• Hypercholesterolemia (blood, congenital, diagnosis)
• Hypertension (blood, chemically induced, diagnosis)
• Male
• Middle Aged
• Platinum (blood)
• Testicular Neoplasms (blood, diagnosis, drug therapy)
• Treatment Outcome
• Young Adult