Dataset Information

Comparison of the modified low-dose cytarabine and etoposide with decitabine therapy for elderly acute myeloid leukemia patients unfit for intensive chemotherapy.

ABSTRACT: To overcome unsatisfactory results of classical low-dose cytarabine (LDAC) of cytarabine ?20 mg twice daily (BID) subcutaneously for 10 days for patients with elderly acute myeloid leukemia (eAML), we evaluated a modified LDAC (mLDAC) of cytarabine 20 mg/m2 BID subcutaneously plus etoposide 50 mg BID orally for 14 days. To determine its feasibility, we compared outcomes of 77 and 42 eAML patients who received, respectively, mLDAC and decitabine (DAC; 20 mg/m2 intravenously daily for 5 days), which has shown better outcomes compared to those of classical LDAC. Most of baseline characteristics of two groups were well balanced. The mLDAC group had a higher complete response (CR) rate compared to the DAC group (46.8% vs. 19.0%, P < 0.01). Unlike the classical LDAC, mLDAC induced CR in patients with adverse cytogenetics, with its rate similar to that of the DAC group (33.3% vs. 20.0%; P = 0.58). Meanwhile, mucositis, neutropenic fever and invasive aspergillosis were more frequently observed in the mLDAC group, with no difference in early mortality between two groups (P > 0.05). The median overall survival rates of the mLDAC and DAC groups were comparable (8.7 vs 8.3 months, respectively, P = 0.35), presumably because the advantage of higher CR rate in the mLDAC group was offset by beneficial effects of marrow response, which is observed dominantly in the DAC group. Our results suggested that the outcomes of classical LDAC could be improved by modest modifications, to be comparable to those of DAC.

SUBMITTER: Shin SH

PROVIDER: S-EPMC5814177 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Comparison of the modified low-dose cytarabine and etoposide with decitabine therapy for elderly acute myeloid leukemia patients unfit for intensive chemotherapy.

Shin Seung-Hwan SH Cho Byung-Sik BS Park Sung-Soo SS Cho Sung-Yeon SY Jeon Young-Woo YW Yoon Jae-Ho JH Yahng Seung-Ah SA Lee Sung-Eun SE Lee Dong-Gun DG Eom Ki-Seong KS Kim Yoo-Jin YJ Lee Seok S Min Chang-Ki CK Cho Seok-Goo SG Kim Dong-Wook DW Lee Jong-Wook JW Min Woo-Sung WS Kim Hee-Je HJ

Oncotarget 20171223 5

To overcome unsatisfactory results of classical low-dose cytarabine (LDAC) of cytarabine ≤20 mg twice daily (BID) subcutaneously for 10 days for patients with elderly acute myeloid leukemia (eAML), we evaluated a modified LDAC (mLDAC) of cytarabine 20 mg/m<sup>2</sup> BID subcutaneously plus etoposide 50 mg BID orally for 14 days. To determine its feasibility, we compared outcomes of 77 and 42 eAML patients who received, respectively, mLDAC and decitabine (DAC; 20 mg/m<sup>2</sup> intravenously ...[more]

PMID: 29464037

Similar Datasets

Project description:BACKGROUND:Front-line therapy for elderly or unfit patients with acute myeloid leukaemia (AML) remains unsatisfactory with poor outcomes and excessive toxicity. We studied a new low-intensity regimen of cladribine combined with low-dose cytarabine alternating with decitabine, aimed at improving outcomes in this population. Based on our previous experience, we hypothesised that this combination would be safe and more effective than current approaches with hypomethylating agents. METHODS:In this single-arm, open-label, single-centre phase 2 study, we enrolled patients aged 60 years or older with previously untreated AML or high-risk myelodysplastic syndrome who had adequate organ function and an Eastern Cooperative Oncology Group performance status of 2 or less. Patients were treated with cladribine plus low-dose cytarabine for two 28-day cycles alternating with decitabine for two 28-day cycles, for up to 18 cycles. Induction therapy (cycle 1) consisted of cladribine 5 mg/m2 intravenously over 1-2 h on days 1-5 and cytarabine 20 mg subcutaneously twice daily on days 1-10. Patients who had remission during this induction regimen moved on to consolidation therapy (cladribine 5 mg/m2 intravenously over 1-2 h on days 1-3 and cytarabine 20 mg twice daily on days 1-10, alternating with decitabine 20 mg/m2 intravenously on days 1-5). The primary outcome measure was disease-free survival. Secondary outcomes were overall survival, proportion of patients achieving complete response, proportion of patients achieving response, toxicity, and induction mortality. All treated patients were included in the analyses. This trial is ongoing and is registered with ClinicalTrials.gov, number NCT01515527. FINDINGS:Between Feb 17, 2012, and July 6, 2017, 118 patients were enrolled and treated, among whom 48 (41%) had an adverse karyotype, 20 (17%) had therapy-related AML, 18 (15%) had treated secondary AML, and 20 (17%) had TP53 mutations. Median disease-free survival was 10·8 months (IQR 5·4-25·9). 80 (68%) patients achieved objective response: 69 (58%) achieved a complete response and 11 (9%) patients had complete response with incomplete count recovery. The median overall survival was 13·8 months (6·9-28·6). The regimen was well tolerated, with one (1%) death within the first 4 weeks and eight (7%) deaths within the first 8 weeks. The most common non-haematological adverse events of grade 3 or worse were infection (88 [75%] patients), elevated total bilirubin (26 [22%] patients), rash (13 [11%] patients), and nausea (13 [11%] patients). INTERPRETATION:The combination of cladribine and low-dose cytarabine alternating with decitabine appears to be a safe and highly effective regimen for the treatment of elderly or unfit patients with newly diagnosed AML. Further testing of this regimen is warranted, and could help to provide a new, effective option for reduced-intensity therapy in this population. FUNDING:Part supported by the National Institutes of Health.

Dataset Information

Comparison of the modified low-dose cytarabine and etoposide with decitabine therapy for elderly acute myeloid leukemia patients unfit for intensive chemotherapy.

Publications

Comparison of the modified low-dose cytarabine and etoposide with decitabine therapy for elderly acute myeloid leukemia patients unfit for intensive chemotherapy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets