Pharmacokinetics (PK) and Pharmacodynamics (PD) of Epoetin Alfa in Anemic Cancer Patients Receiving Cycling Chemotherapy.

Epoetin alfa is a recombinant human erythropoietin (EPO). The objective of this study was to compare the PK/PD of epoetin alfa after a fixed dose (40,000 IU) once weekly (QW) regimen to those after the weight based (150 IU/kg) 3 times per week (TIW) regimen for 4 weeks in healthy subjects and for 6 weeks in anemic cancer patients. In this randomized, open-label, parallel, multi-center study, PK profiles were determined during Week 1 and Week 3 in healthy subjects. For cancer patients, PK profiles were determined during Week 1 when patients were receiving chemotherapy and an optional one during Week 3 when patients were not receiving chemotherapy. Of the 33 enrolled cancer patients who received as least one dose of Epoetin alfa (safety population), 29 were evaluable for PK and 27 were evaluable for PD. Of the safety population (82% had solid tumors), ECOG scores were 0 (48%), 1 (42%), and 2 (9%). None of the patients had bone or kidney metastasis. Their ages and body weights ranged from 31–77 yrs (mean 59.2 yrs) and 50.9 –94.1 kg (mean 70.8 kg), respectively. Mean serum EPO concentrations in the cancer patients during Week 1 were higher than during Week 3. In general, the concentration-time profiles and PK parameters of anemic cancer subjects were different from those in healthy subjects during Week 1 but similar to healthy subjects during Week 3. Mean (SD) PK parameters are listed in following table. Epoetin alfa was safe and well tolerated after the two regimens in this study. The 40,000 IU QW regimen had a higher C_max, higher exposure to epoetin alfa/erythropoietin in serum (in terms of AUC_0-7days), and a lower clearance (CL/F) than the 150 IU/kg TIW regimen. Despite these PK differences, time-profiles of changes in PD parameters and their AUC (% reticulocytes, hemoglobin, and total RBCs) were similar. Mean (SD) PK parameters