A single-blind, randomised, vehicle-controlled dose-finding study of recombinant human granulocyte colony-stimulating factor (lenograstim) in patients undergoing chemotherapy for solid cancers and lymphoma.
This study evaluated the effect of glycosylated recombinant human granulocyte colony-stimulating factor (rHuG-CSF; lenograstim) on neutrophil granulocyte counts and on cells of other haematopoietic lineages in 66 patients with solid cancer or lymphoma who received myelosuppressive chemotherapy. Beginning 1 day after completion of chemotherapy, patients received lenograstim (at dosages of 0.5, 2, 5 or 10 micrograms/kg) or vehicle subcutaneously once daily for 14 consecutive days. Compared with vehicle, lenograstim significantly accelerated neutrophil recovery after chemotherapy in a dose-dependent manner. Mean neutrophil counts recovered to > 1.0 x 10(9) cells/l by day 13 in the vehicle group compared with days 11, 10, 8 and 7 in the 0.5, 2, 5 and 10 micrograms/kg lenograstim groups, respectively. Doses of 0.5 and 2 micrograms/kg of lenograstim had a significant effect on the duration of neutropenia (< 1.0 x 10(9) cells/l), the area under the absolute neutrophil count (ANC) curve and the time to ANC nadir. The dose of 5 micrograms/kg additionally decreased the total area of neutropenia and gave the narrowest range of values for all neutrophil parameters, while the 10 micrograms/kg dose brought no added benefit. A dose-response effect of lenograstim on time to neutrophil recovery was observed both for patients who received chemotherapy on a single day (n = 35) and for those who received chemotherapy over several days (n = 29). Based on these findings, a dose of 5 micrograms/kg/day was chosen for further trials.
Seymour
A M
AM
Clinical Oncology Unit, Guy's Hospital, London, U.K.
de Campos
E
E
Thatcher
N
N
De Greve
J
J
Cunningham
D
D
Howell
A
A
Tueni
E
E
Bron
D G
DG
Steward
W P
WP
Berdel
W E
WE
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D015251:Epirubicin / Q000627:therapeutic use; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D000078224:Lenograstim; D007958:Leukocyte Count; D008223:Lymphoma / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy; D009503:Neutropenia / Q000188:drug therapy*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D016037:Single-Blind Method
D000276:Adjuvants, Immunologic; D000903:Antibiotics, Antineoplastic; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D015251:Epirubicin; D000078224:Lenograstim