A dose- and schedule-finding study of darbepoetin alpha for the treatment of chronic anaemia of cancer

R E Smith Jr, N S Tchekmedyian, D Chan, L A Meza, D W Northfelt, R Patel, M Austin, A B Colowick, G Rossi, J Glaspy, R E Smith Jr, N S Tchekmedyian, D Chan, L A Meza, D W Northfelt, R Patel, M Austin, A B Colowick, G Rossi, J Glaspy

Abstract

A multicentre study evaluated the efficacy and safety of darbepoetin alpha administered weekly (QW), every 3 weeks (Q3W), and every 4 weeks (Q4W) to anaemic patients with cancer not concurrently receiving chemotherapy or radiotherapy. The QW portion (n=102) was an open-label, sequential, dose-escalation design; cohorts received darbepoetin alpha QW by subcutaneous (s.c.) injection at 0.5, 1.0, 2.25, or 4.5 micro g kg(-1) week(-1) for 12 weeks. The 12-week placebo-controlled, double-blind Q3W (6.75 micro g kg(-1)) and Q4W (6.75 or 10.0 micro g kg(-1)) schedules (n=86), which enrolled different patients, took place after the QW schedule and were followed by a 12-week, open-label phase. Patients were evaluated for change in haemoglobin end points and red blood cell transfusions, serum darbepoetin alpha concentration, and safety. Selected domains of health-related quality of life (HRQOL) were measured. With QW dosing, at least 70% of each cohort had a haemoglobin increase from baseline of > or =2 g dl(-1) or a concentration > or =12 g dl(-1) (haematopoietic response). In the 4.5 micro g kg(-1) QW cohort, all patients achieved a haematopoietic response (100%; 95% confidence interval (CI)=100, 100). In the Q3W and Q4W schedules, all cohorts had at least 60% of patients who achieved a haematopoietic response. Darbepoetin alpha effectively increases haemoglobin concentration when given QW, Q3W, or Q4W. Less-frequent administration may benefit patients with chronic anaemia of cancer and their caregivers alike.

Figures

Figure 1
Figure 1
Disposition of patients.
Figure 2
Figure 2
Proportion of patients with haematopoietic response.
Figure 3
Figure 3
Mean change in haemoglobin over double-blind and open-label phases of Q3W and Q4W schedules.
Figure 4
Figure 4
Adverse events that occurred with ⩾15% incidence in either treatment group in the Q3W and Q4W schedules.

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