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 ≤ 11.0 g dl(−1)) who had non-myeloid malignancies received NESP weekly (2.25 mcg 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. © 2001 Cance Cancer Research Campaign