Lenograstim for the treatment of neutropenia in patients receiving ganciclovir for cytomegalovirus infection: a randomised, placebo-controlled trial in AIDS patients.
This phase IIa, randomised, single-blind, placebo-controlled study was conducted to determine the dose of recombinant human granulocyte colony-stimulating factor (lenograstim) suitable for use in AIDS patients. The study was conducted at 27 European AIDS/HIV centres, and recruited 69 AIDS patients with an initial episode or relapse of cytomegalovirus infection (neurological site excluded) and an absolute neutrophil count (ANC) < or = 1.0 x 10(9)/L upon diagnosis or between days 1 and 12 of ganciclovir (GCV) treatment. The patients were randomised to placebo (n = 14) or one of four lenograstim arms: 150 microg/m2/d (the standard onco-haematology dose, n = 13) or 100 (n = 13), 50 (n = 15), or 25 microg/m2/d (n = 14). In all groups, the planned dose of GCV was 10 mg/kg/d for 21 d. Median ANC at weeks 2 and 3 was significantly higher in each lenograstim group than in the placebo group (p = 0.05). At week 3, median ANC (x 10(9)/L) was 0.7 in the placebo group, compared with 6.0, 7.4, 4.5, and 2.0 in the 150, 100, 50, and 25 microg2/d lenograstim groups, respectively. Median ANC was not significantly different between the 150, 100, and 50 microg/m2/d lenograstim groups at any time point, but significantly higher in the 50 than in the 25 microg/m2/d group at weeks 2 (p = 0.05) and 3 (p = 0.02). Lenograstim was generally well tolerated, leading to no severe adverse events. In conclusion, lenograstim 50 microg/m2/d is suitable for the treatment of ganciclovir-induced neutropenia and is safe. These results should help the physician choose an optimal and cost-efficient regimen for patients with AIDS-related neutropenia when rHuG-CSF support is indicated.
Dubreuil-Lemaire
M L
ML
Clinical Immunology, Hôpital Henri Mondor, Créteil, France.
Gori
A
A
Vittecoq
D
D
Panelatti
G
G
Tharaux
F
F
Palisses
R
R
Gharakhanian
S
S
Rozenbaum
W
W
D017088:AIDS-Related Opportunistic Infections / Q000150:complications / Q000188:drug therapy; D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000633:toxicity; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects; D001772:Blood Cell Count; D003586:Cytomegalovirus Infections / Q000150:complications / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D005260:Female; D015774:Ganciclovir / Q000008:administration & dosage / Q000009:adverse effects*; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000633:toxicity; D006760:Hospitalization; D006801:Humans; D007239:Infections / Q000209:etiology; D000078224:Lenograstim; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy*; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000633:toxicity; D013997:Time Factors
D000276:Adjuvants, Immunologic; D000998:Antiviral Agents; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000078224:Lenograstim; D015774:Ganciclovir