Doctors Guide Publishing Limited

ATLANTA, GA -- December 9, 2007 -- Weekly administration of 2-chlorodeoxyadenosine (CDA) in patients with hairy cell leukemia was as toxic as daily dosing and tended to delay recovery from toxicity, according to a phase 3, randomized study of 100 patients.

The results were presented in a poster here on December 8 at the 49th American Society of Hematology (ASH) Annual Meeting and Exposition by Reinhard Zenhäusern, MD, Clinical Investigator, Inselspital Bern, Bern, Switzerland, and other researchers.

"Weekly administration of CDA cannot be recommended for [hairy cell leukemia] patients with severe baseline pancytopenia," the researchers said.

Daily CDA dosing is the standard in hairy cell leukemia, but severe neutropenia is common. Recent research suggested that weekly administration over a longer period can reduce infectious complications and febrile episodes.

Fifty patients each were assigned to receive CDA at 0.14 mg/kg daily for 5 days or weekly for 5 weeks in the Bern group's study.

Responses, white cell counts, and toxicities were monitored for 10 weeks after treatment began.

The primary outcome measure was the mean white blood cell count over the first 6 weeks of the study. Secondary outcomes included response rates and remission durations, other hematologic toxicities, infections, hospitalizations, and transfusion requirements.

Mean white cell counts were somewhat greater in the weekly CDA group compared with the daily dosing group (3.0 vs 2.2 million/mL, respectively) but the difference was not significant.

No significant differences were seen in other outcome measures, including the efficacy parameters as well as those related to toxicity.

The same proportion (86%) of patients in each group showed objective responses, although more patients receiving CDA daily had complete responses (60% vs 41%, significance not reported).

Nadir values for leucocytes and granulocytes were lower with daily CDA, but recovery of white cell counts was slower in patients in the weekly-dose group. For example, median granulocyte count reached 1 million/mL on about day 23 in the daily-dose group, while it was day 36 when the weekly-dose group reached this level.

White cell counts in the weekly-CDA group remained below those of the daily-dose group through the end of the 10-week study.

Despite the lower white counts, however, clinical complications did not differ markedly. For example, 44% of the daily-dose group and 40% of the weekly-dose group had acute infections.


[Presentation title: A Randomized Study of Daily Versus Weekly Administration of 2-Chlorodeoxyadenosine in Patients With Hairy Cell Leukemia. Abstract 1352]