Efficacy of a new formulation of lenograstim (recombinant glycosylated human granulocyte colony-stimulating factor) containing gelatin for the treatment of neutropenia after consolidation chemotherapy in patients with acute myeloid leukemia.
The efficacy and safety of a new formulation of lenograstim (recombinant glycosylated granulocyte colony-stimulating factor) prepared by switching the stabilizer from human serum albumin (HSA) to gelatin was investigated for the treatment of neutropenia after consolidation chemotherapy in patients with acute myeloid leukemia (AML). The results obtained in the study using the gelatin-containing formulation (gelatin-lenograstim) were retrospectively compared to those obtained from a placebo-controlled double-blind randomized study (AML-DBT) using the HSA-containing formulation (HSA-lenograstim). The median time of neutrophil recovery to > or = 1000/mm3 was significantly shorter in the gelatin-lenograstim group (14 days) than in the placebo group (21 days, P = .0001), and there was no significant difference between the gelatin-lenograstim group and the HSA-lenograstim group (14.5 days of AML-DBT, P = .5462). The incidences of febrile neutropenia were significantly reduced in the gelatin-lenograstim group (24/43, 55.8%) compared to the placebo group (58/64, 90.6%, P < .0001). The incidence of fever and antibiotic use was also significantly lower in the gelatin-lenograstim group (69.8% and 83.7%, respectively) than in the placebo group (92.2%, P = .0034, and 96.9%, P = .0285, respectively). However, between the 2 groups there were no differences in the number of patients who had infectious episodes. No serious adverse drug reactions ascribed to gelatin-lenograstim were encountered. These results demonstrate that gelatin-lenograstim exerted beneficial effects in the acceleration of neutrophil recovery and in the reduction of fever, febrile neutropenia, and antibiotic use, and its efficacy was equivalent to HSA-lenograstim. Therefore, we concluded that the gelatin-lenograstim formulation, which offers no risk of virus contamination and can be stored at room temperature, is more beneficial than the HSA-lenograstim formulation.
Takeshita
A
A
Department of Medicine, III, Hamamatsu University School of Medicine, Shizuoka, Japan. akihirot@hama-med.ac.jp
Saito
H
H
Toyama
K
K
Horiuchi
A
A
Kuriya
S
S
Furusawa
S
S
Tsuruoka
N
N
Takiguchi
T
T
Matsuda
T
T
Utsumi
M
M
Shiku
H
H
Matsui
T
T
Egami
K
K
Tamura
K
K
Ohno
R
R
D000208:Acute Disease; D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000592:standards; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004311:Double-Blind Method; D004339:Drug Compounding; D005260:Female; D005334:Fever / Q000453:epidemiology; D005780:Gelatin / Q000494:pharmacology; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000592:standards*; D006801:Humans; D015994:Incidence; D007239:Infections; D000078224:Lenograstim; D007951:Leukemia, Myeloid / Q000150:complications* / Q000628:therapy; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy*; D009504:Neutrophils / Q000166:cytology; D010349:Patient Compliance; D010919:Placebos; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000592:standards; D012709:Serum Albumin / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D000900:Anti-Bacterial Agents; D010919:Placebos; D011994:Recombinant Proteins; D012709:Serum Albumin; D016179:Granulocyte Colony-Stimulating Factor; D000078224:Lenograstim; D005780:Gelatin