Japanese Journal of Clinical Oncology Advance Access originally published online on April 24, 2009
Japanese Journal of Clinical Oncology 2009 39(7):425-430; doi:10.1093/jjco/hyp038
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© The Author (2009). Published by Oxford University Press. All rights reserved
A Pharmacokinetic and Dose Escalation Study of Pegfilgrastim (KRN125) in Lung Cancer Patients with Chemotherapy-induced Neutropenia
1 Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka
2 Division of Internal Medicine, National Cancer Center Hospital
3 Department of Medical Oncology, Kinki University School of Medicine
4 Division of Internal Medicine, Kinki-chuo Chest Medical Center, Osaka
5 Department of Hospital Pharmacy, Keio University School of Medicine, Tokyo
6 Internal Medicine and Thoracic Oncology, National Cancer Center Hospital East, Chiba, Japan
For reprints and all correspondence: Nobuyuki Yamamoto, Division of Thoracic Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777, Japan. E-mail: n.yamamoto{at}scchr.jp
Received September 30, 2008; accepted March 22, 2009
Objective: The aim of this study was to investigate the safety, pharmacokinetic and pharmacodynamic profiles of pegfilgrastim (KRN125), a long-acting granulocyte colony-stimulating factor, in lung cancer patients with chemotherapy-induced neutropenia.
Methods: Eighteen Japanese lung cancer patients who had experienced severe neutropenia (absolute neutrophil counts <0.5 x 109 cells/l) were enrolled. Six patients were sequentially enrolled in each pegfilgrastim dose cohort (dose levels of 30, 60 or 100 µg/kg). Patients received the same chemotherapy regimen as in their previous cycle and pegfilgrastim was injected subcutaneously the day after chemotherapy ended in each treatment cycle. Pharmacokinetic, pharmacodynamic and safety analyses were performed.
Results: Dose-limiting toxicity and serious adverse events related to pegfilgrastim were not observed in any patients. Pegfilgrastim antibodies were not detected. Maximum serum concentrations and area under the serum concentration–time curves of pegfilgrastim were dependent on the pegfilgrastim dose in a non-linear manner. Of the 18 patients, severe neutropenia occurred in 4 (22.2%), and, of these, 1 patient (5.5%) required rescue treatment by filgrastim.
Conclusions: A single dose of pegfilgrastim increases the serum concentration of pegfilgrastim for several days in a dose-dependent manner and is not associated with significant toxicity. Good efficacy of pegfilgrastim for the prevention of severe neutropenia was observed at all dose levels. Based on these data, further studies are warranted to determine the recommended dose of pegfilgrastim for Japanese patients with chemotherapy-induced neutropenia.
Key Words: pegfilgrastim • subcutaneous • pharmacokinetics • neutropenia