Randomized Phase 2 Dose-finding Study of Weekly Administration of Darbepoetin Alpha in Anemic Patients with Lung or Ovarian Cancer Receiving Multicycle Platinum-containing Chemotherapy

Objective: This is the first clinical trial for Japanese to evaluate the dose-response and determine the clinically effective dose of darbepoetin alpha by weekly subcutaneously administration in anemic patients with lung cancer or ovarian cancer receiving chemotherapy.

Methods: Eligible patients were required to have anemia (hemoglobin level of <or=11.0 g/dl). Patients were randomized in a 1:1:1 ratio to receive darbepoetin alpha (1.0, 2.25 or 4.5 microg/kg) subcutaneously once a week for up to 12 weeks. The study drug was withheld from patients who had a hemoglobin level >15.0 g/dl (for men) or 14.0 g/dl (for women), and reinstated at 50% of the previous weekly dose when the hemoglobin level decreased to <or=13.0 g/dl. Quality-of-life assessments were conducted using the Japanese version of the Functional Assessment of Cancer Therapy-anemia (FACT-an) questionnaire.

Results: Hemoglobin response rate was 31.6%, 55.6% and 70.3% in 1.0, 2.25 and 4.5 microg/kg groups, respectively. The dosages of 2.25 and 4.5 microg/kg thus met the clinically effective dose criterion of at least 50% of patients achieving a hemoglobin response. The FACT-fatigue subscale had a high internal consistency with Cronbach's alpha score. Although no improvement in FACT-fatigue subscale score from baseline to the end of the treatment phase was confirmed for any dose group, there was a correlation between FACT-fatigue subscale score and hemoglobin concentration. Darbepoetin alpha appears to be well tolerated in this setting and no dose-dependent adverse events were observed.

Conclusions: Darbepoetin alpha alleviated anemia caused by platinum-based chemotherapy, and the dosage of 2.25 microg/kg was the lowest dose that met the clinically effective dose criteria when administered once weekly.