Azacitidine in fludarabine-refractory chronic lymphocytic leukemia: a phase II study.

Abstract

BACKGROUND:

Treatment of fludarabine-refractory disease in patients with chronic lymphocytic leukemia (CLL) remains a challenge. Because a recent genome-wide methylation analysis of CLL cells suggested that demethylation therapy might be beneficial in CLL, we conducted a phase II trial with the hypomethylating agent azacitidine in patients with recurrent fludarabine-refractory CLL.

PATIENTS AND METHODS:

Nine patients with recurrent fludarabine-refractory Rai stage IV CLL (median age, 74 years; range, 49-81 years) were enrolled. Azacitidine (75 mg/m(2)) was administered by subcutaneous injection daily for 7 consecutive days every 3 to 8 weeks, and the data were analyzed at a median follow-up of 9 months (range 3-47 months).

RESULTS:

The trial was prematurely discontinued because of lack of response and slow accrual. The number of cycles administered ranged from 1 to 6. Three patients received 1 cycle, 3 patients received 2 cycles, and the remaining 3 patients received 4, 5, or 6 cycles. Side effects included grade 2 or 3 infectious episodes (resulting from immunosuppression and drug-induced neutropenia), diarrhea, rash, vomiting, anemia, and thrombocytopenia. One patient experienced reduction of hepatosplenomegaly and a substantial increase in platelet count after 4 cycles of therapy. However this response did not qualify as a partial response according to the National Cancer Institute International Workshop on CLL (NCI-IWCLL) criteria. At a median follow-up of 9 months after the start of azacitidine treatment, 3 patients (33%) who went on to receive other treatments were alive.

CONCLUSIONS:

Although no partial or complete responses occurred in these heavily pretreated patients, the encouraging response in 1 of these patients may warrant further studies to investigate the effects of azacitidine in CLL.

• Authors: Asifa Malik, Mahran Shoukier, Guillermo Garcia-Manero, William Wierda, Jorge Cortes, Susan Bickel, Michael J Keating, Zeev Estrov
• Journal: Clinical lymphoma, myeloma & leukemia (Clin Lymphoma Myeloma Leuk) Vol. 13 Issue 3 Pg. 292-5 (Jun 2013) ISSN: 2152-2669 [Electronic] United States
• PMID: 23265768 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Antimetabolites, Antineoplastic
• Azacitidine

Topics

• Aged
• Aged, 80 and over
• Antimetabolites, Antineoplastic (adverse effects, therapeutic use)
• Azacitidine (adverse effects, therapeutic use)
• DNA Methylation (drug effects)
• Female
• Humans
• Leukemia, Lymphocytic, Chronic, B-Cell (drug therapy, genetics)
• Male
• Middle Aged
• Treatment Outcome