A pharmacokinetic and dose escalation study of pegfilgrastim (KRN125) in lung cancer patients with chemotherapy-induced neutropenia

Nobuyuki Yamamoto, Ikuo Sekine, Kazuhiko Nakagawa, Minoru Takada, Masahiro Fukuoka, Yusuke Tanigawara, Nagahiro Saijo

Research output: Contribution to journalArticle

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Abstract

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 × 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.

Original languageEnglish
Pages (from-to)425-430
Number of pages6
JournalJapanese Journal of Clinical Oncology
Volume39
Issue number7
DOIs
Publication statusPublished - 2009

Fingerprint

Neutropenia
Lung Neoplasms
Pharmacokinetics
Drug Therapy
pegfilgrastim
Serum
Safety
Granulocyte Colony-Stimulating Factor
Neutrophils
Antibodies

Keywords

  • Neutropenia
  • Pegfilgrastim
  • Pharmacokinetics
  • Subcutaneous

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Radiology Nuclear Medicine and imaging

Cite this

A pharmacokinetic and dose escalation study of pegfilgrastim (KRN125) in lung cancer patients with chemotherapy-induced neutropenia. / Yamamoto, Nobuyuki; Sekine, Ikuo; Nakagawa, Kazuhiko; Takada, Minoru; Fukuoka, Masahiro; Tanigawara, Yusuke; Saijo, Nagahiro.

In: Japanese Journal of Clinical Oncology, Vol. 39, No. 7, 2009, p. 425-430.

Research output: Contribution to journalArticle

Yamamoto, Nobuyuki ; Sekine, Ikuo ; Nakagawa, Kazuhiko ; Takada, Minoru ; Fukuoka, Masahiro ; Tanigawara, Yusuke ; Saijo, Nagahiro. / A pharmacokinetic and dose escalation study of pegfilgrastim (KRN125) in lung cancer patients with chemotherapy-induced neutropenia. In: Japanese Journal of Clinical Oncology. 2009 ; Vol. 39, No. 7. pp. 425-430.
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abstract = "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 × 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.",
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AU - Takada, Minoru

AU - Fukuoka, Masahiro

AU - Tanigawara, Yusuke

AU - Saijo, Nagahiro

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AB - 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 × 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.

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