Fax: (011) 49 761 270 3697
Superiority of prolonged low-dose azanucleoside administration?†
Results of 5-aza-2′-deoxycytidine retreatment in high-risk myelodysplasia patients
Article first published online: 13 MAR 2006
Copyright © 2006 American Cancer Society
Volume 106, Issue 8, pages 1744–1750, 15 April 2006
How to Cite
Rüter, B., Wijermans, P. W. and Lübbert, M. (2006), Superiority of prolonged low-dose azanucleoside administration?. Cancer, 106: 1744–1750. doi: 10.1002/cncr.21796
See related editorial on pages 1650-2 and accompanying article on pages 1794-803, this issue.
- Issue published online: 4 APR 2006
- Article first published online: 13 MAR 2006
- Manuscript Accepted: 21 DEC 2005
- Manuscript Revised: 25 NOV 2005
- Manuscript Received: 29 SEP 2005
- DNA methylation;
The optimal treatment duration with decitabine (DAC) in patients with myelodysplastic syndromes (MDS) remains a matter of debate. Although at least 2 consolidating courses after best response usually are performed, the response to treatment after disease recurrence has not been systematically studied to date.
In the current study, the authors report on 22 of 108 patients with MDS (20%) treated with low-dose DAC in 3 Phase II trials who received DAC as retreatment at the time of disease recurrence.
According to the International Prognostic Scoring System (IPSS) at the time of initial treatment, 5 of 22 patients (23%) had a score of intermediate-1 (Int-1), 4 patients (18%) had a score of Int-2, and 13 patients (59%) were scored as high-risk. Patients initially received a median of 6 courses of DAC (range, 2 courses-6 courses), which resulted in a complete remission (complete response [CR]) in 12 of the 22 patients (55%). Retreatment with DAC at the time of disease recurrence was initiated at a median of 11 months (range, 3 mos-27 mos) after the last course of initial treatment. With regard to DAC retreatment, patients received a median of 3 courses (range, 1 courses-6 courses), with 10 of 22 patients (45%) responding (1 with a CR and 2 with partial remissions [partial response (PR)]; all 3 patients achieved a CR at the time of initial treatment) and 7 patients demonstrating a hematologic improvement (HI) (at the time of initial treatment there were 2 CRs, 4 PRs, and 1 HI). Twelve of the 22 patients (55%) did not demonstrate any objective responses to retreatment, including 4 patients with primary resistance to the first course of retreatment. The median survival of all patients from the initiation of the first DAC course was 27.5 months (range, 15 mos-50+ mos). The median survival of 43 patients who also had achieved a response to the initial treatment with DAC but who received best supportive care (n = 33 patients) or induction chemotherapy (n = 10 patients) was 18 months (range, 5 mos-72 mos). Second responders to DAC retreatment were found less frequently in the IPSS high-risk group compared with nonresponders (40% vs. 83%). Age, French–American–British classification subtype, serum lactate dehydrogenase level at retreatment, and previous response to DAC were not found to strongly differ between the groups; however, the subgroups were too small to perform a statistical analysis.
Retreatment with DAC was found to result in objective responses in 45% of previously DAC-responsive patients. However, the quality and duration of the second disease remissions were found to be inferior. Therefore, DAC-responsive patients might derive more clinical benefit from continuation of the initial treatment. Cancer 2006. © 2006 American Cancer Society.