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Journal ArticleDOI

Decitabine for myelodysplastic syndromes: dose comparison in a real world clinical setting.

08 Jan 2019-Leukemia & Lymphoma (Leuk Lymphoma)-Vol. 60, Iss: 7, pp 1731-1739
TL;DR: 15 mg/m2/d decitabine is associated with a lower incidence of hematological toxicities and longer OS and may be more suitable for patients with relatively lower risk.
Abstract: We retrospectively studied 133 myelodysplastic syndrome patients receiving decitabine during January 2009 and September 2017. The dose of 15 mg/m2/d (n = 83) and 20 mg/m2/d (n = 50) had comparable overall response rates (ORR) (51.8% vs. 52.00%) and complete remission rate (CRR) (15.66% vs. 22.00%). The 15 mg/m2/d group had a lower incidence of grade 3/4 neutropenia (60.24% vs. 88.00%, p < .05) and thrombocytopenia (65.06% vs. 88.00%, p < .05). The 15 mg/m2/d group had a longer median overall survival (OS) (21.60 months vs. 15.23 months, p = .02). The same results were seen in refractory anemia with excess blasts (RAEB) patients: The 15 mg/m2/d group also had comparable ORR, CRR, decreased hematological toxicities and longer OS. Further analysis suggested that survival benefit of 15 mg/m2/d group was mainly in those patients with lower risk stratification. In conclusion, 15 mg/m2/d decitabine is associated with a lower incidence of hematological toxicities and longer OS and may be more suitable for patients with relatively lower risk.
Citations
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Journal ArticleDOI
TL;DR: HMA combined with chemotherapy can rescue the 2-year OS with less favorable cytogenetic stratification to some extent and for patients with similar older age and risk stratification, combination therapy even had a lower long-term OS regardless of the intensity of combined chemotherapy.
Abstract: Aim: This meta-analysis aimed to compare the efficacy, survival benefit and safety of hypomethylating agents (HMA) monotherapy and combination with chemotherapy in patients with intermediate/high-risk MDS or AML. Methods: Related articles published between January 2009 and April 2019 were selected and patients were separated as monotherapy group and combination group for meta-analysis. Studies on HMA combination therapy were further divided into two subgroups according to the intensity of combined chemotherapy. Meanwhile, subgroups with similar patients' baseline characteristics were selected for further analysis. Complete response (CR) rate, overall response (ORR) rate, two-year overall survival (OS) rate, one-month and 24-month death rate and the proportion of adverse events (AE) were pooled and compared. Results: 21 RCT or cohort studies with 1764 patients (1266 patients for monotherapy group and 498 patients for HMA combination group) were selected for meta-analysis. For the pooled data, the age of patients was significantly younger and the percentage of patients with favorable/intermediate cytogenetic risk was significantly higher in the HMA combination group than that in the HMA monotherapy group. Combination therapy group had a significantly higher CR and ORR rate (55% vs 22%, P=0.000 for CR and 67% vs 42%, P=0.000 for ORR), and a higher two-year OS rate (37% vs 21%, P=0.000). However, the incidence of infection and gastrointestinal disorder was significantly higher (51% vs 23% for infection, P=0.000; 21% vs 0% for gastrointestinal disorder, P=0.000) in combination group. In subgroups with different intensity of combined chemotherapy, all baseline characteristics were compatible except that the percentage of patients with favorable/intermediate cytogenetic risk was significantly lower (63% vs 88%, P=0.000) in the HMA + high-intensity chemotherapy subgroup, and this group presented with a lower CR and ORR rate (46% vs 65% for CR, P=0.000; 57% vs 79% for ORR, P=0.000), but a compatible two-month to 24-month death rate compared with HMA + low-intensity chemotherapy subgroup (9% vs 14% for 2-month death rate, P=0.060; 58% vs 65% for 24-month death rate, P=0.242). In subgroup with similar patients' baseline characteristics, 208 and 205 patients were included in combination group and HMA monotherapy group, respectively. Although combination group had a significantly higher CR rate (62% vs 24%, P=0.000) and ORR rate (68% vs 48%, P=0.000), it finally had a lower two-year OS (30% vs 45%, P=0.001) compared with monotherapy group, and the death rate was significantly higher since the ninth month in combination therapy group than that in the monotherapy group (42% vs 31%, P=0.032). In this subgroup, patients with HMA+ high-intensity chemotherapy had a compatible CR, ORR and 1.5-year OS rate as compared with baseline-compatible patients with HMA + low-intensity chemotherapy. Conclusions: HMA combined with chemotherapy could increase CR rate and ORR rate in all patients. HMA combined with high-intensity chemotherapy can rescue the 2-year OS with less favorable cytogenetic stratification to some extent. For patients with similar older age and risk stratification, combination therapy even had a lower long-term OS regardless of the intensity of combined chemotherapy.

5 citations


Cites background from "Decitabine for myelodysplastic synd..."

  • ...Ren (2019)[33]† Retrospective cohort study Decitabine (20 or 15 mg/m2/day, 5 days every 28 days) N/A N/A 31....

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Journal ArticleDOI
25 Jun 2022-Cancers
TL;DR: Recent developments in nucleoside transporters are reviewed, including their transport characteristics, their role in the regulation of hematopoiesis, and their potential involvement in the occurrence of adverse hematological side effects due to nucleosid drug treatment.
Abstract: Simple Summary Anticancer nucleoside analogs are promising treatments that often result in damaging toxicities and therefore ineffective treatment. Mechanisms of this are not well-researched, but cellular nucleoside transport research in mice might provide additional insight given transport’s role in mammalian hematopoiesis. Cellular nucleoside transport is a notable component of mammalian hematopoiesis due to how mutations within it relate to hematological abnormities. This review encompasses nucleoside transporters, focusing on their inherent properties, hematopoietic role, and their interplay in nucleoside drug treatment side effects. We then propose potential mechanisms to explain nucleoside transport involvement in blood disorders. Finally, we point out and advocate for future research areas that would improve therapeutic outcomes for patients taking nucleoside analog therapies. Abstract Anticancer nucleoside analogs produce adverse, and at times, dose-limiting hematological toxicities that can compromise treatment efficacy, yet the mechanisms of such toxicities are poorly understood. Recently, cellular nucleoside transport has been implicated in normal blood cell formation with studies from nucleoside transporter-deficient mice providing additional insights into the regulation of mammalian hematopoiesis. Furthermore, several idiopathic human genetic disorders have revealed nucleoside transport as an important component of mammalian hematopoiesis because mutations in individual nucleoside transporter genes are linked to various hematological abnormalities, including anemia. Here, we review recent developments in nucleoside transporters, including their transport characteristics, their role in the regulation of hematopoiesis, and their potential involvement in the occurrence of adverse hematological side effects due to nucleoside drug treatment. Furthermore, we discuss the putative mechanisms by which aberrant nucleoside transport may contribute to hematological abnormalities and identify the knowledge gaps where future research may positively impact treatment outcomes for patients undergoing various nucleoside analog therapies.

2 citations

Journal ArticleDOI
TL;DR: It is demonstrated that a very-low-dose decitabine schedule has an appreciable response and survival rate, as well as appreciable tolerance and medical compliance for treating MDS.
Abstract: Decitabine is a hypomethylating drug that is used to treat myelodysplastic syndrome (MDS) at a recommended dose and schedule (20 mg/m2 per day, for 5 consecutive days). However, due to its relatively high incidence of side effects and its effects on neoplastic cells, many studies have begun to explore the clinical application of a low dose of decitabine for treating MDS. In this retrospective study, we examined the effects of a very-low-dose decitabine schedule for treating MDS. A total of 13 patients diagnosed with de novo MDS received a schedule of intravenous decitabine administration at 6 mg/m2 per day for 7 days, repeated every 4 weeks. The complete response rate was 30.8%, and the overall response rate was 69.2%. In patients with complete remission, the median time to granulocyte recovery greater than 0.5 × 109/L during complete remission (CR) was 15 days. In patients with remission, the median time to granulocyte recovery greater than 0.5 × 109/L was 10.5 days. The 1-year survival rate was 72.7% and the median survival was 28.0 months. In summary, we demonstrated that a very-low-dose decitabine schedule has an appreciable response and survival rate, as well as appreciable tolerance and medical compliance for treating MDS.

1 citations

References
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Journal ArticleDOI
TL;DR: Recent progress in the evolution of adverse effects grading systems is updated and the development of CTCAE v3.0 is reviewed, which represents an international collaboration and consensus of the oncology research community.

2,321 citations

Book
05 Dec 2005

1,624 citations

Journal ArticleDOI
15 Apr 2006-Cancer
TL;DR: Aberrant DNA methylation, which results in leukemogenesis, is frequent in patients with myelodysplastic syndromes (MDS) and is a potential target for pharmacologic therapy.
Abstract: BACKGROUND Aberrant DNA methylation, which results in leukemogenesis, is frequent in patients with myelodysplastic syndromes (MDS) and is a potential target for pharmacologic therapy. Decitabine indirectly depletes methylcytosine and causes hypomethylation of target gene promoters. METHODS A total of 170 patients with MDS were randomized to receive either decitabine at a dose of 15 mg/m2 given intravenously over 3 hours every 8 hours for 3 days (at a dose of 135 mg/m2 per course) and repeated every 6 weeks, or best supportive care. Response was assessed using the International Working Group criteria and required that response criteria be met for at least 8 weeks. RESULTS Patients who were treated with decitabine achieved a significantly higher overall response rate (17%), including 9% complete responses, compared with supportive care (0%) (P < .001). An additional 12 patients who were treated with decitabine (13%) achieved hematologic improvement. Responses were durable (median, 10.3 mos) and were associated with transfusion independence. Patients treated with decitabine had a trend toward a longer median time to acute myelogenous leukemia (AML) progression or death compared with patients who received supportive care alone (all patients, 12.1 mos vs. 7.8 mos [P = 0.16]; those with International Prognostic Scoring System intermediate-2/high-risk disease, 12.0 mos vs. 6.8 mos [P = 0.03]; those with de novo disease, 12.6 mos vs. 9.4 mos [P = 0.04]; and treatment-naive patients, 12.3 mos vs. 7.3 mos [P = 0.08]). CONCLUSIONS Decitabine was found to be clinically effective in the treatment of patients with MDS, provided durable responses, and improved time to AML transformation or death. The duration of decitabine therapy may improve these results further. Cancer 2006. © 2006 American Cancer Society.

1,419 citations


"Decitabine for myelodysplastic synd..." refers methods in this paper

  • ...The current recommended regimen of decitabine is 20mg/m(2)/d for consecutive 5 days, which has been proved to be superior to the 3-day regimen in efficacy and safety [5,11]....

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Journal ArticleDOI
Phuong L. Nguyen1
TL;DR: The epidemiology and clinical and pathologic features of MDS and pertinent diagnostic and prognostic classifications are discussed, with a brief overview of treatment options.
Abstract: Myelodysplastic syndromes (MDS) are a heterogeneous group of bone marrow disorders that affect mostly the elderly and have a variable probability of progression to acute leukemia. The diagnosis of MDS rests largely on a critical morphologic review of blood and bone marrow slides, with careful correlation with other clinical and essential laboratory data, including cytogenetics. This article discusses the epidemiology and clinical and pathologic features of MDS and pertinent diagnostic and prognostic classifications, with a brief overview of treatment options. Other considerations in the differential diagnosis are also briefly outlined.

1,103 citations

Journal ArticleDOI
01 Mar 2004-Blood
TL;DR: It is concluded that decitabine is effective in myeloid malignancies, and low doses are as or more effective than higher doses.

796 citations


"Decitabine for myelodysplastic synd..." refers background in this paper

  • ...Several clinical trials have examined the efficacy of decitabine of varying doses in MDS patients, including the 3-day regimen (15mg/m(2) every 8 h for three consecutive days every 6 weeks) [7,11,12], the 5-day regimen (20mg/m(2)/d for 5 days every four weeks) [13,14], and the 10-day regimen of either 10 or 15mg/m(2)/d [15]....

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  • ...In an in vivo pilot study, 15 versus 20mg/m(2)/d decitabine achieved similar levels of demethylation of Alu and LINE1 elements [15]....

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