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.

Abstract

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.

• Authors: Yukito Ichinose, Takashi Seto, Yutaka Nishiwaki, Yuichiro Ohe, Yoshiharu Yamada, Koji Takeda, Nagahiro Saijo, Tomomitsu Hotta
• Journal: Japanese journal of clinical oncology (Jpn J Clin Oncol) Vol. 40 Issue 6 Pg. 521-9 (Jun 2010) ISSN: 1465-3621 [Electronic] England
• PMID: 20508073 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Hematinics
• Hemoglobins
• Platinum Compounds
• Erythropoietin
• Darbepoetin alfa

Topics

• Anemia (blood, chemically induced, drug therapy)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Darbepoetin alfa
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Erythropoietin (administration & dosage, adverse effects, analogs & derivatives)
• Female
• Hematinics (administration & dosage, adverse effects)
• Hemoglobins (analysis)
• Humans
• Lung Neoplasms (complications, drug therapy)
• Male
• Middle Aged
• Ovarian Neoplasms (complications, drug therapy)
• Platinum Compounds (adverse effects, therapeutic use)
• Quality of Life