Serum pegfilgrastim concentrations during recovery of absolute neutrophil count in patients with cancer receiving pegfilgrastim after chemotherapy.
OBJECTIVE
To examine the serum concentrations of pegfilgrastim during recovery of absolute neutrophil count (ANC) in patients with cancer who received pegfilgrastim after chemotherapy.


METHODS
Retrospective analysis.


METHODS
Data were pooled from seven pegfilgrastim registrational clinical trials: four open-label phase I or II studies and three randomized phase II or III studies.


METHODS
A total of 370 patients with non-small cell lung cancer, Hodgkin's lymphoma, non-Hodgkin's lymphoma, or breast cancer.


RESULTS
Chemotherapy was given every 3 weeks, and pegfilgrastim was given once/chemotherapy cycle, 24 hours after chemotherapy completion. Data were available from 187 patients for the serum pegfilgrastim concentration analysis and from 319 patients for the ANC data analysis. Recovery of ANC to normal levels (>or= 1 x 10(3)/mm3) correlated well with the decline of pegfilgrastim concentrations to subtherapeutic levels; this inverse correlation was observed across different tumor types. By day 12 after pegfilgrastim administration, all patients experienced ANC recovery to normal levels, and none had a serum pegfilgrastim concentration above 2 ng/ml, considered the lowest concentration to elicit clinically meaningful granulopoiesis. After administration of pegfilgrastim, a steady postnadir recovery of the ANC to normal levels was noted, and postnadir peaks of 30 x 10(3)/mm3 or higher were observed in only three patients.


CONCLUSIONS
Serum concentrations of pegfilgrastim were consistently cleared to subtherapeutic levels by day 12 after pegfilgrastim administration, and subtherapeutic pegfilgrastim levels were predicted by ANC recovery to 1 x 10(3)/mm3 or greater.
Yang
Bing-Bing
BB
Department of Pharmacokinetics and Drug Metabolism, Amgen Inc., Thousand Oaks, California 91320-1799, USA. byang@amgen.com
Kido
Anna
A
Shibata
Atsuko
A
D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000188:drug therapy; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D004305:Dose-Response Relationship, Drug; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood* / Q000627:therapeutic use*; D006801:Humans; D007958:Leukocyte Count; D008228:Lymphoma, Non-Hodgkin / Q000097:blood / Q000188:drug therapy; D009369:Neoplasms / Q000097:blood* / Q000188:drug therapy*; D009504:Neutrophils / Q000187:drug effects* / Q000473:pathology; D011092:Polyethylene Glycols; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins; D012189:Retrospective Studies; D013997:Time Factors
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; C455861:pegfilgrastim; D011092:Polyethylene Glycols; D000069585:Filgrastim