title: A phase II dose finding study of darbepoetin alpha and filgrastim for the management of anaemia and neutropenia in chronic hepatitis C treatment.
abstract: Dose reductions of pegylated interferon alpha and ribavirin may be avoided by using growth factors. This phase II clinical trial assesses the dose, efficacy and safety of darbepoetin alpha and filgrastim for treatment of anaemia and neutropenia associated with combination therapy for hepatitis C virus (HCV). Chronic hepatitis C patients (n = 101) received pegylated interferon alpha-2b (1.5 mug/kg once weekly) and ribavirin (800-1400 mg once daily). Patients with anaemia [haemoglobin (Hb) </= 10.5 g/dL] received darbepoetin alpha (3 mug/kg once every 2 weeks); the dose was titrated to achieve a Hb level of 12.0 g/dL. Patients with neutropenia [absolute neutrophil count (ANC) </= 0.75 x 10(9)/L] received filgrastim with the dose titrated from 150 mug QW to 300 mug thrice weekly to maintain ANC >/= 0.75 x 10(9)/L and <10 x 10(9)/L. During antiviral therapy, 52% of patients required darbepoetin alpha, filgrastim or both. Hb at the time of darbepoetin alpha initiation was 10.2 +/- 0.4 g/dL. After 81 days of darbepoetin alpha, Hb increased by 1.9 +/- 1.0 g/dL to 12.1 +/- 1.1 g/dL (P < 0.0001). Filgrastim resulted in a significant increase in ANC [0.75 +/- 0.16 x 109/L to 8.28 +/- 5.67 x 10(9)/L (P < 0.0001)]. In treatment-naïve patients, 48% achieved sustained virological response (SVR), whereas 27% of patients previously treated with a course of pegylated interferon alpha achieved SVR. Low viral load, nongenotype 1 and treatment with growth factors were independently associated with SVR. Mild and severe anaemia were associated with quality of life impairments. Darbepoetin alpha resulted in an improvement in the Vitality domain of Short Form-36. No significant adverse events were related to growth factors. During anti-HCV therapy, filgrastim improved neutropenia and darbepoetin alpha improved both anaemia and quality of life. Future randomized clinical trials are needed to establish the impact of growth factors in improving sustained virological response.
authors.affiliation: Center for Liver Diseases, Inova Fairfax Hospital, Annandale, VA 22003-6800, USA. zobair.younossi@inova.com
authors.forename: Z M
authors.initials: ZM
authors.lastname: Younossi
authors.forename: F H
authors.initials: FH
authors.lastname: Nader
authors.forename: C
authors.initials: C
authors.lastname: Bai
authors.forename: R
authors.initials: R
authors.lastname: Sjogren
authors.forename: J P
authors.initials: JP
authors.lastname: Ong
authors.forename: R
authors.initials: R
authors.lastname: Collantes
authors.forename: M
authors.initials: M
authors.lastname: Sjogren
authors.forename: D
authors.initials: D
authors.lastname: Farmer
authors.forename: L
authors.initials: L
authors.lastname: Ramsey
authors.forename: K
authors.initials: K
authors.lastname: Terra
authors.forename: H
authors.initials: H
authors.lastname: Gujral
authors.forename: C
authors.initials: C
authors.lastname: Gurung
authors.forename: M
authors.initials: M
authors.lastname: Srishord
authors.forename: Y
authors.initials: Y
authors.lastname: Fang
mesh_terms: D000328:Adult; D000740:Anemia / Q000188:drug therapy* / Q000523:psychology; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use; D000068256:Darbepoetin alfa; D004921:Erythropoietin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D006397:Hematinics / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D006454:Hemoglobins / Q000032:analysis; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000188:drug therapy*; D011092:Polyethylene Glycols; D011788:Quality of Life; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D006397:Hematinics; D006454:Hemoglobins; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D004921:Erythropoietin; D016179:Granulocyte Colony-Stimulating Factor; D000068256:Darbepoetin alfa; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b; D000069585:Filgrastim