BEP chemotherapy has been established as the standard of care for germ cell tumors, with marked improvements in patient survival 1. In treating germ cell tumors with BEP chemotherapy, the lower total dose and dose intensity of bleomycin and the lower dose intensity of etoposide may be responsible for poor outcomes 5. However, in our case, because of multiple large liver metastases, the patient presented with severe liver dysfunction and, in addition, kidney dysfunction. Therefore, we needed to modify the chemotherapy regimen. As etoposide is metabolized into inactive forms in the liver 6, dose reduction by 50% in patients with bilirubin between 1.5 and 3 mg/dl is recommended 6,7. On the basis of these reports, we reduced etoposide by 50% for the first cycle of chemotherapy. As 60% of bleomycin is cleared by the kidney 6, the dose of bleomycin was reduced to 25 mg/body instead of 30 mg/body. As one of the major side effects of cisplatin is renal toxicity, the administration of cisplatin requires dose adjustments in patients with renal dysfunction and cisplatin is not recommended for patients with creatinine clearance below 60 ml/min 8. Nedaplatin is a second-generation platinum derivative with reduced nephrotoxicity that exerts antitumor activity against various cancers, including testicular, gynecological, and lung carcinomas 4,9–11. We substituted nedaplatin for cisplatin to reduce nephrotoxicity at the time of chemotherapy induction. As liver and kidney dysfunction was improved immediately after induction of the chemotherapy, a full dose of standard BEP chemotherapy was administered from the second cycle of the chemotherapy.
We speculate that there could be two reasons for kidney dysfunction in this patient. First, the patient’s huge liver metastasis and portal vein thrombosis is similar to the situation of hepatorenal syndrome in patients with chronic previous liver disease. The occurrence of this syndrome is related to the mechanisms associated with ascites development, involving vasoconstriction, low renal perfusion, water and sodium retention, increased plasma volume, and consequent overflow at the splanchnic level 12. Second, TLS may also occur before chemotherapy 3, and the patient actually presented with hyperuricemia, hyperpotassemia, and kidney dysfunction before chemotherapy, fulfilling diagnostic criteria for TLS 3. TLS is an oncological emergency that may occur during chemotherapy for highly chemosensitive malignancies 13. The release of intracellular substances accompanying extensive tumor cell death is considered to be the cause of this syndrome. The production and excretion of a high volume of uric acid causes the deposition of uric acid crystals in the collecting ducts, which results in the development of uric acid nephropathy 14. In our case, the patient’s uric acid level was very high (13.9 mg/dl) before starting chemotherapy. Thus, it is possible the patient’s renal failure is because of TLS. The treatment of TLS involves adequate hydration and administration of allopurinol or rasburicase. Before 2002, antihyperuricemic drug therapy was limited to allopurinol. As allopurinol acts by decreasing the formation of uric acid, it is ineffective in reducing levels of uric acid developed before treatment 3. Rasburicase, a recombinant urate oxidase, which converts uric acid into the more soluble allantoin, was approved for children in 2002 and adults in 2009 15. Rasburicase is now a standard of care for patients at high risk of TLS 15. We administered rasburicase at the time of chemotherapy induction, and serum uric acid rapidly decreased to 0.1 mg/dl at 24 h after administration.
We also used CHDF to prevent the progression of renal failure and TLS. Compared with intermittent hemodiafiltration, the major advantage of CHDF is its reduced rate of fluid removal. CHDF is generally better tolerated than conventional intermittent therapy 16. As the general condition of the patient worsened, CHDF was administered at the intensive care unit. To avoid drug clearance by dialysis causing a loss of efficacy, CHDF was stopped during an intravenous infusion of chemotherapy drugs.
TLS is observed most frequently in patients with hematologic malignancies such as acute lymphoblastic leukemia after the initiation of cytotoxic therapy, although it may also occur spontaneously and/or in other tumor types with a high proliferative rate, large tumor burden, or high sensitivity to cytotoxic therapy 3. TLS in patients with testicular cancer is rare, but can be life-threatening 14,17. Testicular cancer is a chemotherapy-sensitive cancer that is a risk factor for the development of TLS. Attention must be paid to the potential risk of TLS in patients of advanced testicular cancer with balky metastasis.
There are no conflicts of interest.
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