title: Pharmacokinetic and pharmacodynamic profiles of subcutaneous administration of continuous erythropoietin receptor activator in lung cancer patients with anemia induced by chemotherapy.
abstract: Continuous erythropoietin receptor activator (C.E.R.A.) is an innovative erythropoiesis-stimulating agent with unique erythropoietin receptor activity and a prolonged half-life. C.E.R.A. is currently in development for the correction of anemia and stable hemoglobin (Hb) control at extended administration intervals in patients with cancer who are receiving chemotherapy. The purpose of this pharmacological study was to evaluate the pharmacokinetic (PK), pharmacodynamic (PD) and safety profiles of C.E.R.A. administered subcutaneously once every 3 weeks (Q3W) in lung cancer patients with anemia induced by chemotherapy. This open-label, multicenter study recruited 46 patients. Entry Hb levels were not more than 11.0 g/dl. Five dose levels of C.E.R.A. (2.1, 4.2, 6.3, 9 and 12 μg/kg) were tested in sequential cohorts of 8-11 patients for 12 weeks. The mean values for C.E.R.A half-life ranged from 143 to 247 h. The maximum serum concentration (C(max)) following the first administration of C.E.R.A. increased in proportion to the dose. The increase of Hb levels occurred in a dose-dependent manner. No serious adverse events reported as being related to C.E.R.A. were observed during the study period. Thrombovascular events were not observed in any patient. Anti-C.E.R.A antibodies were not detected in any patient. Thus, this pharmacological study confirmed the long half-life of C.E.R.A., thereby supporting subcutaneous administration of C.E.R.A. at the Q3W interval. PK and PD parameters demonstrated dose-proportionality over the range of doses tested in this study. Additionally, C.E.R.A. was generally well tolerated.
authors: Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka 411-8777.
authors: Toshiaki
authors: T
authors: Takahashi
authors: Nobuyuki
authors: N
authors: Yamamoto
authors: Tomohide
authors: T
authors: Tamura
authors: Hideo
authors: H
authors: Kunitoh
authors: Yutaka
authors: Y
authors: Nishiwaki
authors: Shunichi
authors: S
authors: Negoro