Pharmacokinetics of novel erythropoiesis stimulating protein (NESP) in cancer patients: preliminary report

Anaemia is a common occurrence in patients with cancer, and currently can be treated in several ways. Novel erythropoiesis stimulating protein (NESP, darbepoetin alfa) was created using site-directed mutagenesis to have 8 more sialic acid side chains than recombinant human erythropoietin (rHuEPO). The additional sialic acid content has resulted in an approximately 3-fold greater half-life relative to rHuEPO in patients with chronic renal failure. This study evaluates the pharmacokinetic profile of NESP in patients receiving multiple cycles of chemotherapy. Anaemic patients (haemoglobin less than or equal to 11.0 g dl(-1)) who had non-myeloid malignancies received NESP weekly (2.25 meg kg(-1) wk(-1)) under the supervision of a physician, starting on day 1 of chemotherapy for 3 chemotherapy cycles given at 3-week intervals. Blood samples were collected during chemotherapy cycles 1 and 3 for pharmacokinetic analysis. All patients were followed for 4 weeks after treatment. NESP was well tolerated by all patients. After a single dose during chemotherapy cycle 1, pharmacokinetic parameters (mean (SD), n) for the first 15 patients were: T-max 86.1 (22.8) h (n = 14); C-max 9.0 (5.1) ng ml(-1) (n = 14); t(1 2.z) 32.6 (11.8) h (n = 7); CL/F 3.7 (1.0) ml h(-1) kg(-1) (n = 7). The subjects for whom all parameters could be calculated may represent a sub-group of the entire population. Similar results were obtained in cycle 3. In addition, haemoglobin response data suggests that, in this patient population, dosing less frequently than the 3 times weekly doses used for rHuEPO may be possible while improving anaemia. (C) 2001 Cancer Research Campaign.