Chemotherapy for primary mediastinal yolk sac tumor in a patient undergoing chronic hemodialysis: a case report

Abstract

Background: The safety and efficacy of chemotherapy for patients undergoing concomitant hemodialysis have not been fully established and optimal doses of anti-cancer drugs and best timing of hemodialysis remains unclear. Although chemosensitive cancers, such as germ cell tumors, treated with chemotherapy should have sufficient dose intensity maintained to achieve the desired effect, many patients with cancer undergoing hemodialysis might be under-treated because the pharmacokinetics of anti-cancer drugs in such patients remains unknown.

Case presentation: We describe a 31-year-old Japanese man with a mediastinal yolk sac tumor treated with surgery followed by five cycles of chemotherapy containing cisplatin and etoposide while concomitantly undergoing hemodialysis. The doses of these agents used in the first cycle were 50% of the standard dose of cisplatin (10 mg/m²) and 60% of the standard dose of etoposide (60 mg/m²) on days 1 through to 5; the doses were subsequently escalated to 75% with both agents. Hemodialysis was started 1 hour after infusions of these agents. Severe hematological toxicities were observed despite successful treatment. During treatment with concurrent hemodialysis, pharmacokinetic analysis of cisplatin was performed and its relationship with adverse effects was assessed. Compared with patients with normal renal function, the maximum drug concentration was higher, and concentration increased in the interval between hemodialysis and the subsequent cisplatin infusion, resulting in a higher area under the curve despite a reduction in the dose to 75% of the standard regimen.

Conclusions: Because of the altered pharmacokinetics pharmacodynamics status of patients with renal dysfunction undergoing hemodialysis, pharmacokinetics pharmacodynamics analysis is deemed to be helpful for effective and safe management of chemotherapy in patients undergoing hemodialysis.

Keywords: Cisplatin; Hemodialysis; Mediastinal yolk sac tumor; Pharmacokinetics; Renal insufficiency.

Fig. 1

Computed tomography scan confirms a solid tumor (53×35 mm) in the anterior mediastinum (arrow)

Fig. 2

Pathological findings of computed tomography-guided biopsy specimen. a Tumor cells with mixed sinusoidal-like, cystic, and papillary structures were observed (hematoxylin and eosin staining, ×20). b Schiller–Duval body was highlighted with white arrow (hematoxylin and eosin staining, ×100). Immunohistochemical staining is positive for cytokeratin AE1/AE3 (×200) (c) and alpha-fetoprotein (d) (×200)

Fig. 3

Schedule of chemotherapy, hemodialysis, and blood sampling. In the third and fourth chemotherapy cycles, cisplatin (15 mg/m²) and etoposide (75 mg/m²) was conducted daily from day 1 through to day 5. Hemodialysis was started 1 hour after infusions of these agents. Venous blood samples were collected five times each day: (1) before cisplatin infusion, (2) immediately after infusion, (3) before hemodialysis, (4) after hemodialysis, and (5) 4 hours after hemodialysis on days 1 to 5. In addition, blood was collected (6) before hemodialysis on day 8 once in each course. CDDP cisplatin, ETP etoposide, HD hemodialysis

Fig. 4

Free cisplatin concentration analysis. The solid and dotted lines show plasma free cisplatin concentration in the third and fourth chemotherapy cycles, respectively. White arrows indicate cisplatin (15 mg/m²) infusions and black two-headed arrows indicate hemodialysis during days 1 to 5. HD hemodialysis