Randomized, dose-escalation study of SD/01 compared with daily filgrastim in patients receiving chemotherapy.
OBJECTIVE
To explore the use of SD/01 (a polyethylene glycol-conjugated filgrastim shown in preclinical studies to have a prolonged half-life) in patients with chemotherapy-induced neutropenia.


METHODS
Thirteen patients with non-small-cell lung cancer were randomized to receive daily filgrastim (5 microg/kg/d) or a single injection of SD/01 (30, 100, or 300 microg/kg) 2 weeks before chemotherapy and again 24 hours after administration of carboplatin and paclitaxel. Pharmacodynamic, pharmacokinetic, and safety analyses were performed.


RESULTS
Peak serum concentrations of SD/01 and the duration of increased serum concentrations were dependent on the SD/01 dose. SD/01 concentrations remained increased longer in patients with chemotherapy-induced neutropenia. Prechemotherapy median absolute neutrophil counts (ANCs) in patients receiving SD/01 were increased in a dose-dependent fashion, with the duration of this effect also being dose dependent. After chemotherapy, median ANC nadirs were similar in the filgrastim cohort and the cohort receiving SD/01 30 microg/kg, with higher nadirs seen in the cohorts receiving SD/01 100 or 300 microg/kg. Dose-limiting toxicities were not noted. CD34(+) cells were mobilized in all cohorts.


CONCLUSIONS
A single dose of SD/01 increases the serum concentration of SD/01 for several days in a dose-dependent fashion and is not associated with significant toxicity. The effects of SD/01 on ANC and CD34(+) cell mobilization are comparable or greater than those achieved with daily filgrastim. The self-regulation of this molecule provides a potential therapeutic advantage in a variety of clinical settings associated with neutropenia.
Johnston
E
E
Thoracic Oncology Program, Duke Comprehensive Cancer Center, Durham, NC 27710, USA.
Crawford
J
J
Blackwell
S
S
Bjurstrom
T
T
Lockbaum
P
P
Roskos
L
L
Yang
B B
BB
Gardner
S
S
Miller-Messana
M A
MA
Shoemaker
D
D
Garst
J
J
Schwab
G
G
D000368:Aged; D018952:Antigens, CD34 / Q000032:analysis; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D019650:Hematopoietic Stem Cell Mobilization; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007958:Leukocyte Count / Q000187:drug effects; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D009504:Neutrophils; D010865:Pilot Projects; D010976:Platelet Count / Q000187:drug effects; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D011994:Recombinant Proteins
D018952:Antigens, CD34; D000970:Antineoplastic Agents; D006454:Hemoglobins; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; C455861:pegfilgrastim; D011092:Polyethylene Glycols; D000069585:Filgrastim