Short-term therapeutic effects of low-dose cytarabine plus surgical resection on elderly patients with trigeminal nerve tumor and safety observation

Abstract Abstract 2624 The incidence of acute myeloid leukemia (AML) increases with age and outcomes for elderly patients remain poor. Furthermore, intensive induction chemotherapy is often unsuitable for elderly patients and can result in significant periods of inpatient care. Recent understanding of leukemia stem cell cycling suggests that prolonged cytotoxic exposure, e.g. >14–21 days, could provide a more effective anti-leukemic effect than the typical 5–7 days schedules during which time very few leukemic stem cells would be likely to undergo cell division. We have been using prolonged low-dose cytarabine schedules as reported 20 years ago (Hellstrom-Lindberg, Brit J Haem,1992;81:503), however we have combined this with oral thioguanine, a purine analogue that may synergize with cytarabine. Concomitant filgrastim or pegfilgrastim was given to minimize neutropenia and for its possible synergizing anti-leukemic effect when combined with cytotoxic agents. Encouraging experience with this schedule in a few relapsed/refractory elderly AML patients prompted us to use this strategy in elderly de-novo patients unsuitable for standard induction. Surprisingly good results prompted us to report our preliminary experience with this novel strategy. This report is a retrospective, single-center analysis of outcomes in elderly patients with AML managed as outpatients in an ambulatory care day unit. Between April 2009 and March 2011, 14 patients with either relapsed/refractory AML (n=5) or de novo AML (n=9) unsuitable for intensive therapy were treated using prolonged, low-dose cytarabine 20mg/m2/day subcutaneously and thioguanine 80mg/day orally. Treatment was given for 21 days followed by a 14 day break after which the schedule was repeated until remission. After obtaining remission, patients received a maintenance schedule consisting of 14 days on treatment with rest periods increasing from 14 to 28 days according to tolerance and time on therapy, with an intention to continue maintenance for 2 years. All patients received the treatment in an ambulatory care unit with supportive care including filgrastim or pegfilgrastim, blood and platelet transfusion as required, regular clinical review and prophylactic antibiotics and antifungal agents. Patient age ranged from 52 to 89 years (median 75y). All patients had intermediate or poor risk cytogenetics. A morphologic remission according to bone marrow aspirate was obtained in 8 patients (57.1%), with relapse seen in 1 patient at 2.6 months follow-up. Remission was maintained in 7 patients (50%) with follow-up ranging from 4.7 to 26.6 months (median 9.7 months), including 1 patient who was refractory to standard first and second-line induction chemotherapy. Refractoriness to treatment occurred in 5 patients (35.7%). Mortality relating to disease progression occurred in 3 patients (21.4%) and 1 patient died secondary to infection. All patients developed grade 3/4 neutropenia and thrombocytopenia but severe mucositis was not seen. The infection rate was low and hospital admission was uncommon. Nausea was common but manageable and significant liver toxicity was not observed. This study demonstrates that effective management of AML in elderly patients can be achieved in the outpatient setting. The data suggests a surprising efficacy for this strategy, with a remission rate comparable to that reported using standard induction chemotherapy but with a potentially favorable toxicity profile. A prospective study is now underway to further evaluate this protocol. Disclosures: Arthur: AMGEN: Honoraria.

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Feasibility of BIBF1120 (nintedanib) combined with low-dose cytarabine in elderly patients with AML ineligible for intensive treatment.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.15_suppl.7053 ◽

2014 ◽

Vol 32 (15_suppl) ◽

pp. 7053-7053 ◽

Cited By ~ 1

Author(s):

Utz Krug ◽

Nicola Knoblauch ◽

Joachim Gerss ◽

Christoph Schliemann ◽

Stefanie Wiebe ◽

...

Keyword(s):

Elderly Patients ◽

Low Dose ◽

Intensive Treatment ◽

Low Dose Cytarabine

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Effect of low-dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor priming (CAG regimen) on the outcome of elderly patients with acute myeloid leukemia

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.7067 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 7067-7067

Author(s):

S. Qian ◽

J. Li ◽

S. Zhang

Keyword(s):

Acute Myeloid Leukemia ◽

Elderly Patients ◽

Myeloid Leukemia ◽

Low Dose ◽

Granulocyte Colony Stimulating Factor ◽

Colony Stimulating Factor ◽

Cytogenetic Aberrations ◽

Stimulating Factor ◽

Low Dose Cytarabine ◽

Acute Myeloid

7067 Background: To evaluate the efficacy and toxicity of low-dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor (G-CSF) protocol in elderly patients with acute myeloid leukemia (AML). Methods: A total of fifty-two elderly patients were enrolled. Twenty-eight patients were male, and 24 were female, with ages ranging from 60 to 81 years (median, 65 years). Complete remission (CR) had not been achieved in five patients after 2 courses of a standard induction regimen including daunorubicin and cytarabine or an equivalent anthracycline-based regimen. Cytogenetic analysis was performed in 40 patients, and unfavourable cytogenetic aberrations were showed in 10 patients. All patients were treated with CAG regimen including low-dose cytarabine (10 mg/m2 per 12 hours, days 1 to 14), aclarubicin (10 mg per day, days 1 to 8), and G-CSF priming (200 μg/m2 per day, days 1 to 14). Results: The overall response rate was 69.2%, and 29 of 52 (55.8%) patients achieved CR, including 23 of 35 (65.8%) patients with previously untreated AML, 6 of 17 (35.2% ) patients with refractory, relapsed and secondary AML, 4 of 9 (44.4%) patients aged over 70 years, 4 of 10 (40.0%) patients with unfavourable cytogenetic aberrations. The early death rate was 7.6%. The median overall survival duration 14 months. Myelosuppression was mild to moderate, severe nonhematologic toxicity was not observed. Conclusions: CAG priming regimen as the induction therapy is well tolerable and effective in elderly patients with AML. No significant financial relationships to disclose.

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Phase I/II study of low-dose cytarabine (LDAC) with sorafenib as first-line therapy of elderly patients with AML or high-risk myelodysplastic syndrome (MDS).

Journal of Clinical Oncology ◽

10.1200/jco.2010.28.15_suppl.6564 ◽

2010 ◽

Vol 28 (15_suppl) ◽

pp. 6564-6564 ◽

Cited By ~ 1

Author(s):

D. A. Macdonald ◽

S. E. Assouline ◽

J. Brandwein ◽

S. Kamel-Reid ◽

E. A. Eisenhauer ◽

...

Keyword(s):

High Risk ◽

Elderly Patients ◽

Myelodysplastic Syndrome ◽

Phase I ◽

Low Dose ◽

First Line ◽

First Line Therapy ◽

Line Therapy ◽

Low Dose Cytarabine

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GRASPA-AML 2012-01 study (NCT01810705): A multicenter, open, randomized phase 2b trial evaluating ERY001 (L-asparaginase encapsulated in red blood cells) plus low-dose cytarabine vs low-dose cytarabine alone, in treatment of newly diagnosed acute myeloid leukemia (AML) elderly patients, unfit for intensive chemotherapy.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.15_suppl.tps7099 ◽

2015 ◽

Vol 33 (15_suppl) ◽

pp. TPS7099-TPS7099 ◽

Cited By ~ 1

Author(s):

Xavier G. Thomas ◽

Emmanuelle Tavernier Tardy ◽

Romain Guieze ◽

Patrice Chevallier ◽

Jean pierre Marolleau ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Elderly Patients ◽

Red Blood Cells ◽

Blood Cells ◽

Myeloid Leukemia ◽

Low Dose ◽

Intensive Chemotherapy ◽

Newly Diagnosed ◽

Low Dose Cytarabine ◽

Acute Myeloid

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VERY-LOW-DOSE CYTARABINE FOR ELDERLY PATIENTS

The Lancet ◽

10.1016/s0140-6736(86)91572-2 ◽

1986 ◽

Vol 327 (8495) ◽

pp. 1436 ◽

Cited By ~ 10

Author(s):

A. Pesce ◽

J.P. Cassuto ◽

J. Bayle ◽

S. Raynaud ◽

J.G. Fuzibet ◽

...

Keyword(s):

Elderly Patients ◽

Low Dose ◽

Low Dose Cytarabine

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Survival Benefit of Novel Drug Combinations Using Hypomethylating Agents for Elderly Patients with Newly Diagnosed Acute Myeloid Leukemia: A Systemic Review

Blood ◽

10.1182/blood-2018-99-115810 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 5182-5182

Author(s):

Pavan Tenneti ◽

Keri R Maher ◽

Mohamed Mokhtar Bakr ◽

Umar Zahid ◽

Saad Ullah Malik ◽

...

Keyword(s):

Valproic Acid ◽

Retinoic Acid ◽

Elderly Patients ◽

Low Dose ◽

Long Term Outcomes ◽

Secondary Aml ◽

Trans Retinoic Acid ◽

All Trans Retinoic Acid ◽

Low Dose Cytarabine

Abstract Background - Acute myeloid leukemia (AML) in elderly patients (>65 years) is associated with poor prognosis with median overall survival (mOS) of 6 months. Hypomethylating agents (Azacytidine (Aza) and Decitabine) are used in elderly patients who are not candidates for intensive chemotherapy. Aza has resulted in complete remission/complete remission with incomplete hematologic recovery (CR/CRi) of 18-27.8% and mOS of 10.4-24.5 months. Decitabine resulted in CR/CRi of 18-47% and mOS of 7.7-8 months. We conducted a systemic review to assess survival benefit of novel combination drug regimens (CDR) involving hypomethylating agent (HMA) in elderly patients with newly diagnosed AML. Methods - Comprehensive literature search was conducted in Medline, Embase and Cochrane database. We included phase I/II studies only that used CDR involving HMA. Results - Initial database search (since inception) lead to 975 studies. After exclusion (duplicates, case reports, relapsed/refractory AML) final analysis included 17 studies(n=540) Ten phase I/II CDR studies involving Aza (n=334) were included. The various drugs used in combination included valproic acid/all trans retinoic acid (n= 42 ,CR/CRi=26.2% mOS= 18.1 m), thalidomide (n= 14,CR/CRi= 29%, mOS= 13.2 m ), gemtuzumab ozogamicin (GO) (n= 142,CR/CRi = 35-44%, mOS= 11 m), lenalidomide (n= 45,CR/CRi=28-44% , mOS= 3-8.2 m), panobinostat (n=38,CR/CRi=10-22.4%, mOS= 8 m), midostaurin (n=12,CR/CRi=25%, mOS=6 m) , entinostat (n=18 ,CR/CRi=0% ,mOS= 6 m ), Seven phase I/II CDR studies(n=206) involving decitabine were included. Drugs used in combination included low dose cytarabine and aclarubicin (n= 85 ,CR/CRi = 64.7% , mOS= 10-12 m ), tosedostat (n=17 ,CR/CRi= 59% mOS= 11.5 m ), bexarotene(n= 4 ,CR/CRi= 0% mOS= 9.2 m), valproic acid(n= 62 ,CR/CRi= 9% mOS= 7.4m) , GO (n= 40,CR/CRi= 45% , mOS= 7m ),bortezomib (n= 10,CR/CRi= 50% ), vorinostat(n = 31,CR/CRi= 30%). Seven studies reported outcomes for patients with adverse cytogenetics separately. Of these, Aza with lenalidomide (n= 11) had a mOS of 9.5 months and with panobinostat (n=12) the overall response rate was 25% and mOS of 7 months. Similarly, decitabine with vorinostat (n = 8) and tosedostat(n =12) resulted in CR/CRi of 25% and 43% respectively. Long term outcomes for these CDR with decitabine were not reported. In two additional studies, valproic acid/all trans retinoic acid given with AZA and low dose cytarabine & aclarubicin with decitabine(p=0.023) showed poor outcome through multivariable cox model analysis. Five studies reported response rates for subgroup of patients with secondary AML using HMA. Of these, Aza with lenalidomide (n= 16) had a CR/CRi = 27% with median response duration of 21.3 weeks, a CR/CRi of 0% with entinostat (n= 18) and CR/CRi of 22% with thalidomide(n=9). Decitabine given with tosadostat (n= 10) had CR/CRi of 60% and with bortezomib(n=3) the CR/CRi was 66%. The long term outcomes were not reported for these patients. Conclusion - Novel combinations involving Aza with valproic acid/all trans retinoic acid, thalidomide, or GO showed similar CR/CRi and mOS compared to Aza alone. Tosedostat, low dose cytarabine, and aclarubicin given in combination with decitabine showed best results with superior CR/CRi and mOS compared to decitabine alone. Bexarotene with decitabine also improved mOS over decitabine alone despite lower CR/CRi. In patients with adverse cytogenetics, Aza with lenalidomide or panobinostat showed superior CR/CRi and mOS. Decitabine given with vorinostat and tosedostat also showed superior CR/CRi. In patients with secondary AML, Aza in combination with lenalidomide or thalidomide and decitabine with tosedostat or bortezomib showed superior CR/CRi. These CDR for patients with adverse cytogenetics and secondary AML need further testing in studies designed with this specific patient population in which long term outcomes are also measured. These CDR need to be evaluated in large, randomized, prospective studies to assess definitive benefit. Disclosures No relevant conflicts of interest to declare.

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