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Residual platinum levels may produce late effects among survivors of testicular cancer
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Long-term circulating platinum exposures corresponded with known late effects such as paraesthesia, hypogonadism, high cholesterol and hypertension among chemotherapy-treated survivors of testicular cancer, according to study results.
“Since the introduction of platinum-based chemotherapy, metastatic testicular cancer has become a curable disease with an excellent prognosis,” Jourik A. Gietema, MD, professor of medical oncology at University of Groningen in the Netherlands, and colleagues wrote. “However, late effects of the treatment may compromise the quality of life after treatment. … A decade ago, Gietema and colleagues found that long-term circulating platinum levels remained detectable up to 20 years after cisplatin combination chemotherapy.”
Studies have confirmed that circulating platinum residuals remain present in serum after platinum-based treatment, according to study background.
Gietema and colleagues sought to determine the relationship between long-term circulating platinum levels and known long-term late effects of treatment for testicular cancer. They collected serum and 24-hour urine samples from survivors of testicular cancer treated with cisplatin-based chemotherapy.
The analysis included data from 240 serum samples from 98 patients — with a median interval between treatment initiation and date of sample of 5 years (range, 0.9-13.2) — as well as single urine samples from 91 patients, with a median interval of 6.6 years after chemotherapy (range, 2.8-13.2).
To build a population pharmacokinetic model, the researchers simultaneously measured platinum data alongside cisplatin dose, age, weight and height. Using this model, the researchers determined area under the curve (AUC) between 1 year and 3 years after treatment for each patient, used as an estimate of long-term exposure to platinum.
The median follow-up was 9 years after chemotherapy (range, 3-15).
Patients received a median cumulative cisplatin dose of 809 mg (range, 554-1,713). Circulating platinum levels rapidly decreased between 1 year and 3 years following treatment.
The total administered dose of cisplatin significantly corresponded with a long-term platinum AUC at 1 to 3 years (r = .517; P < .001). Age at chemotherapy initiation corresponded with long-term platinum AUC; however, this correlation ceased after the researchers adjusted for renal function.
No correlation occurred between platinum AUC and weight, BMI or body surface area at chemotherapy initiation.
Median serum creatinine levels appeared significantly lower before vs. 1 year after chemotherapy (74 vs. 86 μmol/L; P < .001). The median serum creatinine at follow-up was 88 μmol/L.
Creatinine clearance before chemotherapy correlated negatively with platinum AUC at 1 to 3 years (r = .213; P = .04); the association remained negative 1 year after surgery (r = .272; P = .008) and at follow-up (r = .276; P = .007).
Patients with paraesthesia had a higher platinum AUC (30.9 vs. 27 μg/L per month) than patients without paraesthesia (P = .021). Further, the researchers observed higher platinum AUC in patients with hypogonadism (OR = 1.1; 95% CI, 1.02-1.18), elevated LDL-cholesterol levels (OR = 1.07; 95% CI, 1-1.13) or hypertension (OR = 1.1; 95% CI, 1.01-1.18).
The researchers acknowledged the use of predicted values for platinum AUC as a study limitation.
“This association between healthy tissue damage in cancer survivors and long-term platinum exposure should be considered during treatment decisions and follow-up care in testicular cancer patients,” Gietema and colleagues wrote. “Hence, further research on healthy tissue damage caused by long-term platinum exposure is needed.” – by Cameron Kelsall
Disclosure: The researchers report no relevant financial disclosures.
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