A pharmacokinetic and dose escalation study of pegfilgrastim (KRN125) in lung cancer patients with chemotherapy-induced neutropenia.
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 10(9) cells/l) were enrolled. Six patients were sequentially enrolled in each pegfilgrastim dose cohort (dose levels of 30, 60 or 100 microg/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.
Yamamoto
Nobuyuki
N
Division of Thoracic Oncology, Shizuoka Cancer Center, Sunto-gun, Shizuoka, Japan. n.yamamoto@scchr.jp
Sekine
Ikuo
I
Nakagawa
Kazuhiko
K
Takada
Minoru
M
Fukuoka
Masahiro
M
Tanigawara
Yusuke
Y
Saijo
Nagahiro
N
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009503:Neutropenia / Q000139:chemically induced / Q000378:metabolism*; D017239:Paclitaxel / Q000008:administration & dosage; D011092:Polyethylene Glycols; D011379:Prognosis; D011994:Recombinant Proteins; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; C455861:pegfilgrastim; D011092:Polyethylene Glycols; D016190:Carboplatin; D017239:Paclitaxel; D000069585:Filgrastim