An epigenetic approach to the treatment of advanced MDS; the experience with the DNA demethylating agent 5-aza-2′-deoxycytidine (decitabine) in 177 patients
- 7 October 2005
- journal article
- research article
- Published by Springer Science and Business Media LLC in Annals of Hematology
- Vol. 84 (S1), 9-17
- https://doi.org/10.1007/s00277-005-0012-1
Abstract
During the last 10 years, three European phase II studies were performed to investigate the treatment of elderly patients with myelodysplastic syndrome (MDS) with low-dose 5-aza-2′-deoxycytidine (decitabine, DAC). All these European trial data were reviewed on the basis of the International Prognostic Scoring System (IPSS) risk criteria and the response criteria as recently published by an international working group. To investigate the results in a larger cohort of patients and to determine risk factors, all data were pooled with some observations from the PCH 95-06 US phase II study. The response rate in the 177 patients evaluated (median age 70 years) was 49%. The median response duration was 36 weeks, and the median survival was 15 months. Analysis of the data according to sex, age, French–American–British classification, percentage of blasts in the bone marrow, IPSS risk group, lactate dehydrogenase and cytogenetics did not reveal any factor predictive of response. Overall, 69% of patients benefited, including those with stable disease during therapy. Response duration was significantly shorter with increasing risk (according to the IPSS classification). Haemoglobin level and neutrophil count showed an inverse correlation to the IPSS classification. Univariate analysis showed a significantly inferior survival for elderly patients (>75 years of age) and for those with high levels of serum lactate dehydrogenase (LDH) (more than two times the normal values). Patients with high-risk cytogenetic abnormalities according to the IPSS risk criteria showed better overall survival than those with intermediate-risk abnormalities. When analysed according to the IPSS risk classification, high-risk patients had worse survival prospects following decitabine therapy than those with intermediate risk; however, compared to the originally reported IPPS outcomes for high-risk patients, they probably showed better survival. During the treatment period, 18% of the patients progressed towards acute leukaemia. Decitabine showed a rather low toxicity profile in this elderly patient group. In conclusion, low-dose decitabine is an active drug for the treatment of MDS patients, even for those older than 75 years with bad prognostic characteristics.Keywords
This publication has 18 references indexed in Scilit:
- Approval Summary: Azacitidine for Treatment of Myelodysplastic Syndrome SubtypesClinical Cancer Research, 2005
- Phase II Study of R115777, a Farnesyl Transferase Inhibitor, in Myelodysplastic SyndromeJournal of Clinical Oncology, 2004
- Demethylation of a hypermethylated P15/INK4B gene in patients with myelodysplastic syndrome by 5-Aza-2′-deoxycytidine (decitabine) treatmentBlood, 2002
- 5-Azacytidine and 5-aza-2′-deoxycytidine as inhibitors of DNA methylation: mechanistic studies and their implications for cancer therapyOncogene, 2002
- DNA methylation and gene silencing in cancer: which is the guilty party?Oncogene, 2002
- Impact of Azacytidine on the Quality of Life of Patients With Myelodysplastic Syndrome Treated in a Randomized Phase III Trial: A Cancer and Leukemia Group B StudyJournal of Clinical Oncology, 2002
- Randomized Controlled Trial of Azacitidine in Patients With the Myelodysplastic Syndrome: A Study of the Cancer and Leukemia Group BJournal of Clinical Oncology, 2002
- Cytogenetic responses in high-risk myelodysplastic syndrome following low-dose treatment with the DNA methylation inhibitor 5-aza-2'-deoxycytidineBritish Journal of Haematology, 2001
- Continuous infusion of low-dose 5-Aza-2′-deoxycytidine in elderly patients with high-risk myelodysplastic syndromeLeukemia, 1997
- The evaluation of low-dose cytarabine in the treatment of myelodysplastic syndromes: A phase-III intergroup studyAnnals of Hematology, 1992