Annual Meeting Proceedings Part 1 - American Society of Clinical ...

284s Genitourinary Cancer
4528 Poster Discussion Session (Board #7), Sat, 8:00 AM-12:00 PM and
12:00 PM-1:00 PM
Association of long-term exposure to circulating platinum with adverse late
effects in testicular cancer survivors. Presenting Author: Hink Boer, Department
of Medical Oncology, University Medical Center Groningen, Groningen, Netherlands
Background: Successful platinum(Pt)-based chemotherapy for testicular cancer
(TC) comes at the price of late cardiovascular morbidity and neurotoxicity.
Damage induced by circulating Pt could be an etiological mechanism. We
investigated the relation between circulating Pt and late effects. Methods: In 96
consecutive TC patients (med age 29 [17-53] at chemotherapy), 3 serum
samples and a 24h-urine sample were collected on several time-points med 5 yrs
(1-13) after treatment. Pt concentrations ([Pt]) were measured with a sensitive
voltammetric method (Lancet 2000, 355:1075). Measured [Pt] combined with
cisplatin dose, age, weight and height were analyzed simultaneously to construct
a population pharmacokinetic (PK) model using NONMEM. Based on the PK
parameters of each patient, individual [Pt] at 1, 3, 5, 10 yrs after start and AUC
were calculated. Cardiovascular status, paresthesia and markers of vascular
damage were assessed after a med follow-up (FU) of 9 yrs (3-15). Results: Decay
of [Pt] was best described by a two compartment model. Mean terminal T1/2 was
3.7 (�0.3) yrs. At all time-points [Pt] correlated with cisplatin dose and renal
function during treatment. [Pt] at 3 yrs correlated with systolic blood pressure
(BP) (r�.32, p�0.01) and creatinine clearance (CRCL) (r�-.25, p�0.02) at FU.
Patients with increased BP had higher Pt AUCs than patients with normal BP
(table). Pt AUCs were higher in patients with paresthesia (table). Conclusions:
Known late effects of cisplatin-based chemotherapy such as hypertension and
paresthesia are related to higher circulating [Pt]. Long-term exposure to Pt is
involved in healthy tissue damage in TC survivors.
[Pt] pg/g serum (mean�SD)
AUC 1-5 yrs
(pg/g •day)•103 n 3 yrs 5 yrs
Cisplatin dose
800mg
43
.048*
53
379 �118
.028
433 �140
189 �55
.013
218 �66
960 �250
1109 �316
CRCL (mL/min)
>120