Pharmacokinetics, efficacy and safety of palbociclib and fulvestrant in a patient with hormone receptor-positive, human epidermal growth factor receptor 2 negative metastatic breast cancer with end-stage renal disease undergoing hemodialysis: A case report.

Palbociclib combined with fulvestrant is a standard treatment for hormone receptor-positive, human epidermal growth factor receptor 2 (HER2) -negative metastatic breast cancer. Both agents are mainly eliminated by hepatic metabolism, and it is recognized that no dose adjustment is required for patients with renal impairment according to their prescribing information. However, their pharmacokinetics in patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD) were not studied in their development phases. We here report a case of 62-year-old female with ESRD on HD who was treated with palbociclib and fulvestrant. Palbociclib was initiated at a reduced dose of 100 mg/day (standard dose of 125 mg/day) and fulvestrant at a standard dose of 500 mg/body for multiple metastases. Along with dose adjustment of palbociclib due to hematologic toxicities, stable disease (SD) was maintained for 18 months. We also assessed the pharmacokinetics of palbociclib and fulvestrant at the first dose with HD and at steady state. Although the starting dose of palbociclib was reduced, the area under the concentration-time curve from 0 to 24 h (AUC_0-24) and the maximum concentration (C_max) at steady state were higher than those observed in patients with normal renal function receiving 125 mg/day in a Phase I study. Plasma concentrations of fulvestrant at steady state were almost within the range from the mean minimum concentration (C_min) to the mean C_max in patients receiving 500 mg/body in a Phase II study. This report suggests that palbociclib and fulvestrant combination therapy is manageable and effective in patients with ESRD.