An epigenetic approach to the treatment of advanced MDS; the experience with the DNA demethylating agent 5-aza-2′-deoxycytidine (decitabine) in 177 patients Journal Article
| Authors: | Wijermans, P. W.; Lübbert, M.; Verhoef, G.; Klimek, V.; Bosly, A. |
| Article Title: | An epigenetic approach to the treatment of advanced MDS; the experience with the DNA demethylating agent 5-aza-2′-deoxycytidine (decitabine) in 177 patients |
| 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. © Springer-Verlag 2005. |
| Keywords: | adult; cancer survival; controlled study; aged; aged, 80 and over; middle aged; survival rate; chronic myelomonocytic leukemia; major clinical study; overall survival; genetics; clinical trial; disease course; neutropenia; disease classification; drug efficacy; drug safety; side effect; united states; outcome assessment; anorexia; low drug dose; controlled clinical trial; infection; liver toxicity; multiple cycle treatment; nephrotoxicity; neutrophil count; phase 2 clinical trial; anemia; bleeding; blood toxicity; leukopenia; mucosa inflammation; thrombocytopenia; cohort analysis; cytogenetics; creatinine; hemoglobin; creatinine blood level; hemoglobin blood level; continuous infusion; drug effect; prediction; risk factor; high risk patient; age; risk assessment; drug fever; pneumonia; kaplan-meiers estimate; europe; chromosome aberration; drug fatality; drug induced headache; survival time; cancer regression; correlation analysis; drug antagonism; acute leukemia; disease severity; myelodysplastic syndrome; dna; bone marrow biopsy; systematic review; epigenetics; epigenesis, genetic; cardiovascular disease; drug response; data analysis; scoring system; blood transfusion; drug derivative; remission; remission induction; nausea and vomiting; outcomes research; sepsis; 5 aza 2' deoxycytidine; lactate dehydrogenase; sex difference; pancytopenia; headache; age distribution; pharmacogenetics; leukocyte count; kaplan meier method; liver enzyme; cancer classification; drug dose increase; gender; dna methyltransferase; sleep disorder; dna modification methylases; drug dose regimen; univariate analysis; alopecia; anaphylaxis; chromosome analysis; heart atrium fibrillation; genetic epigenesis; geriatric patient; brain hemorrhage; lactate dehydrogenase blood level; hearing impairment; meta analysis; azacitidine; myelodysplastic syndromes; drug indication; blast cell; refractory anemia; demethylation; enzyme blood level; epigenetic therapy; hemoglobin determination; refractory anemia with excess blasts; refractory anemia with ringed sideroblasts; abnormal substrate concentration in blood; refractory anemia with excess blasts in transformation; decitabine; international prognostic scoring system; myelodysplastic syndrome (mds); myeloblast |
| Journal Title: | Annals of Hematology |
| Volume: | 84 |
| Issue: | 1 Suppl. |
| ISSN: | 0939-5555 |
| Publisher: | Springer |
| Date Published: | 2005-12-01 |
| Start Page: | 9 |
| End Page: | 17 |
| Language: | English |
| DOI: | 10.1007/s00277-005-0012-1 |
| PUBMED: | 16211386 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 50" - "Export Date: 24 October 2012" - "CODEN: AHESF" - "Source: Scopus" |
