A phase II dose finding study of darbepoetin alpha and filgrastim for the management of anaemia and

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Journal of Viral Hepatitis (OnlineEarly Articles).

doi:10.1111/j.1365-2893.2007.00956.x

Abstract

A phase II dose finding study of darbepoetin alpha and filgrastim for the

management of anaemia and neutropenia in chronic hepatitis C treatment

Z. M. Younossi11Center for Liver Diseases, Inova Fairfax Hospital, ndale,

VA, F. H. Nader11Center for Liver Diseases, Inova Fairfax Hospital, ndale,

VA, C. Bai11Center for Liver Diseases, Inova Fairfax Hospital, ndale, VA, R.

Sjogren22Kaiser Permanente Medical Group, Falls Church, VA, J. P. Ong11Center

for Liver Diseases, Inova Fairfax Hospital, ndale, VA, R. Collantes11Center

for Liver Diseases, Inova Fairfax Hospital, ndale, VA, M. Sjogren33Walter

Medical Center, Washington DC, USA, D. Farmer11Center for Liver Diseases,

Inova Fairfax Hospital, ndale, VA, L. Ramsey11Center for Liver Diseases,

Inova Fairfax Hospital, ndale, VA, K. Terra11Center for Liver Diseases,

Inova Fairfax Hospital, ndale, VA, H. Gujral11Center for Liver Diseases,

Inova Fairfax Hospital, ndale, VA, C. Gurung11Center for Liver Diseases,

Inova Fairfax Hospital, ndale, VA, M. Srishord11Center for Liver Diseases,

Inova Fairfax Hospital, ndale, VA and Y. Fang11Center for Liver Diseases,

Inova Fairfax Hospital, ndale, VA1Center for Liver Diseases, Inova Fairfax

Hospital, ndale, VA; 2Kaiser Permanente Medical Group, Falls Church, VA; and

3Walter Medical Center, Washington DC, USA

Zobair M. Younossi, MD, MPH, Center for Liver Diseases at Inova Fairfax

Hospital, 3289 Woodburn Road, Suite 375, ndale, VA 22003-6800, USA. E-mail:

zobair.younossi@...

HCV, hepatitis C virus; SVR, sustained virological response; ANC, absolute

neutrophil count; HRQL, health-related quality of life; CBC, complete blood

count; ETR, end of treatment response; EVR, early virological response.

Abstract

Summary. 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 μg/kg once weekly) and ribavirin (800–1400 mg once daily). Patients with

anaemia [haemoglobin (Hb) ≤ 10.5 g/dL] received darbepoetin alpha (3 μg/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 × 109/L]

received filgrastim with the dose titrated from 150 μg QW to 300 μg thrice

weekly to maintain ANC ≥ 0.75 × 109/L and < 0.0001). Filgrastim resulted in a

significant increase in ANC [0.75 ± 0.16 × 109/L to 8.28 ± 5.67 × 109/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.

http://www.blackwell-synergy.com/doi/abs/10.1111/j.1365-2893.2007.00956.x

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