title: Open-label, randomized study of pegfilgrastim vs. daily filgrastim as an adjunct to chemotherapy in elderly patients with non-Hodgkin's lymphoma.
abstract: Pegfilgrastim is composed of the protein filgrastim to which a 20-kDa polyethylene glycol (PEG) is covalently bound at the N-terminal residue resulting in decreased renal clearance and increased plasma half-life compared with filgrastim. This open-label, randomized, phase 2 study compared two doses of single administration pegfilgrastim (60 and 100 microg/kg) with daily doses of filgrastim (5 microg/kg/day) or no cytokine treatment after standard CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) chemotherapy for non-Hodgkin's lymphoma in 50 elderly patients. The primary endpoint was the duration of grade 4 (severe) neutropenia (absolute neutrophil count < 0.5 x 10(9)/l) in cycle 1. Duration of grade 4 neutropenia in cycle 1 was 2.2 (SD 1.2), 1.5 (SD 1.1), 0.8 (1.2) and 5.0 (2.0) days for patients who received pegfilgrastim 60 microg/kg, pegfilgrastim 100 microg/kg, filgrastim 5 microg/kg and no cytokine, respectively. The baseline characteristics of the pegfilgrastim and filgrastim groups were imbalanced with increased bone-marrow involvement and prior therapy in the former. When the treatment groups were balanced for these risk factors, duration of grade 4 neutropenia was comparable with 2.0 and 3.0 vs. 0.6 and 0.5 days for pegfilgrastim 100 microg/kg and filgrastim patients with and without these risk factors, respectively. The incidence of febrile neutropenia (defined as ANC < 0.5 x 10(9)/l and temperature > 38.2degrees C) was low (10% of patients). Pegfilgrastim was well tolerated with a safety profile similar to daily filgrastim. Once per chemotherapy cycle administration of pegfilgrastim was comparable to filgrastim in this clinical setting.
authors.affiliation: Department of Clinical Haematology and Oncology, Royal Melbourne Hospital, Melbourne, Australia. andrew.grigg@mh.org.au
authors.forename: Andrew
authors.initials: A
authors.lastname: Grigg
authors.forename: Philippe
authors.initials: P
authors.lastname: Solal-Celigny
authors.forename: Peter
authors.initials: P
authors.lastname: Hoskin
authors.forename: Kerry
authors.initials: K
authors.lastname: Taylor
authors.forename: Andrew
authors.initials: A
authors.lastname: McMillan
authors.forename: Roswitha
authors.initials: R
authors.lastname: Forstpointner
authors.forename: Pamela
authors.initials: P
authors.lastname: Bacon
authors.forename: Jennifer
authors.initials: J
authors.lastname: Renwick
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hiddemann
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001315:Australia; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D005060:Europe; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced / Q000517:prevention & control*; D010146:Pain / Q000139:chemically induced; D011092:Polyethylene Glycols; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D011994:Recombinant Proteins; D012449:Safety; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; C455861:pegfilgrastim; D011092:Polyethylene Glycols; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D000069585:Filgrastim; D011241:Prednisone