Pharmacokinetic and pharmacodynamic profiles of subcutaneous administration of continuous erythropoietin receptor activator in lung cancer patients with anemia induced by chemotherapy

Takahashi,Toshiaki; Yamamoto,Nobuyuki; Tamura,Tomohide; Kunitoh,Hideo; Nishiwaki,Yutaka; Negoro,Shunichi

doi:10.3892/ol.2011.398

Pharmacokinetic and pharmacodynamic profiles of subcutaneous administration of continuous erythropoietin receptor activator in lung cancer patients with anemia induced by chemotherapy

Authors:
- Toshiaki Takahashi
- Nobuyuki Yamamoto
- Tomohide Tamura
- Hideo Kunitoh
- Yutaka Nishiwaki
- Shunichi Negoro
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Affiliations: Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka 411-8777, Japan, Department of Internal Medicine, National Cancer Center Hospital, Tokyo 104-0045, Japan, Thoracic Oncology Division, National Cancer Center Hospital East, Chiba 277-8577, Japan, Thoracic Oncology, Hyogo Cancer Center, Hyogo 673-8558, Japan
Published online on: August 29, 2011 https://doi.org/10.3892/ol.2011.398
Pages: 1033-1040

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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 (Cmax) 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.

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