Azacitidine as induction therapy of elderly patients with acute myelogenous leukemia.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6620-6620
Author(s):  
Cyrus Khan ◽  
James M. Rossetti ◽  
Christie Hilton ◽  
Santhosh Sadhashiv ◽  
Sanaullah Khalid ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Acute Myelogenous Leukemia ◽  
Myelogenous Leukemia ◽  
Effective Alternative ◽  
Response Criteria ◽  
Hematological Toxicity ◽  
Newly Diagnosed ◽  
Acute Myelogenous ◽  
Blast Count ◽  
The Mean

6620 Background: Effective alternative treatment of elderly patients (aged ≥ 60 years) with acute myelogenous leukemia (AML) remains challenging. Elderly patients with AML respond poorly to standard induction regimens and have high treatment related mortality. In a prior retrospective analysis of elderly patients with AML performed at our institution, azacitidine (AZA) showed an overall response rate (ORR) of 60% with limited toxicity. Methods: This is a prospective, phase II open-label study using AZA in patients ≥60 years with AML. Inclusion criteria: Newly-diagnosed non-M3 AML and ECOG ≤ 2. Patients with circulating blast count ≥30,000/mcl were treated with hydroxyurea until < 30,000/mcl. AZA was administered at 100 mg/m2 subcutaneously for 5 consecutive days every 28 days until disease progression or significant toxicity. Results: In all, 15 patients were enrolled last follow-up being 8/2/11. The mean age of patients is 74 years (range: 64–82). Mean ECOG score was 1. Mean baseline bone marrow blast count was 52% (range: 25–92%). ORR was 46% (n=7) with complete response (CR) in 3 (20%) patients and partial response (PR) in 2 (13%) patients according to NCI response criteria, and hematologic improvement (HI) in 2 (13%) patients according to IWG response criteria. The mean number of days on treatment was 198 (range: 13–724). The mean time to best response among responders was 95 days (range: 44-279). The mean number of days hospitalized for diagnosis plus treatment or disease-related complication was 19 (range: 5–56), with the majority of therapy administered in an outpatient setting. Mean overall survival (OS) from diagnosis for all patients was 355 days (range: 13–908) and mean OS for responders was 532 days (range: 120–908). Non-hematological toxicity was limited to mild injection site skin reaction and fatigue in 73% (11/15). No treatment-related deaths were observed. The dose and schedule of AZA remained constant in a majority of the patients. Conclusions: This study suggests that a 5-day schedule of SC AZA at 100 mg/m2 to elderly patients with newly-diagnosed AML is a feasible, well-tolerated and effective alternative to standard induction chemotherapy.

Azacitidine in the Treatment of Elderly Patients with Acute Myelogenous Leukemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4164-4164
Author(s):  
Heather L. Benjamin ◽  
James M. Rossetti ◽  
Aaron J. Lampkin ◽  
Christie Hilton ◽  
Entezam Sahovic ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Acute Myelogenous Leukemia ◽  
Research Funding ◽  
Myelogenous Leukemia ◽  
Open Label ◽  
Drug Induced ◽  
Acute Myelogenous ◽  
Prospective Phase ◽  
Blast Count ◽  
The Mean

Abstract Abstract 4164 BACKGROUND Effective treatment of the elderly patient with acute myelogenous leukemia (AML) remains a challenging task. Elderly patients with AML usually respond poorly to standard induction chemotherapy. Response rates in elderly patients are in the range of 30–50% compared to 80–90% in younger patients. Moreover, prolonged hospitalization with treatment related mortality as high as 30% is typical in this older population. In a prior retrospective analysis done at our institution, azacitidine showed an overall response rate of 60% with limited toxicity when administered to patients older than 55 years of age with AML. We present an interim analysis of the first 13 patients enrolled in our prospective, phase II open label study using single agent azacitidine for elderly patients with AML. METHODS This is a prospective, phase II open label study using azacitidine in patients ≥ 60 years with AML. Inclusion criteria: Newly diagnosed AML (de novo or secondary, WHO criteria) and ECOG≤ 2. Promyelocytic (M3) phenotype was excluded. Patients with circulating blast count ≥ 30,000/mcl were treated with hydroxyurea until < 30,000/mcl. Azacitidine was given at a dose of 100 mg/m2 subcutaneously for 5 consecutive days every 28 days until disease progression or significant toxicity. G-CSF was given to patients with neutropenia (ANC < 1000/mcl) during all cycles excluding cycle one. RESULTS Thirteen patients have been enrolled to date. The mean age of patients is 75 years (range: 66–84). The mean baseline ECOG performance score was 1 with a mean during treatment of 1. Mean baseline bone marrow blast count was 57% (range: 21–100%). Overall response rate using the NCI response criteria (IWG criteria for patients with hematological improvement (HI) only) was 46% (6/13): complete response (CR; n=3; 23%), partial response (PR; n=1; 8%), and HI (n=2; 15%). One additional patient had a 94% reduction in marrow blasts, but failed to achieve transfusion independence. The mean number of days on treatment was 171+ (range: 13–606). The mean number of days hospitalized for diagnosis plus treatment or disease related complication was 21 (range: 7–72) with the majority of therapy being given in the outpatient setting. One patient required prolonged hospitalization after going on to allogeneic transplantation. The mean overall survival from diagnosis for all patients was 246+ days (range: 13–606). The mean overall survival for responders was 399+ days (range: 212–606). One patient continues on therapy with azacitidine at 606 days (CR). Of the other responders, one progressed at 420 days and is considering other options (CR), one died from an intra-cranial hemorrhage after receiving Mylotarg for disease progression at 454 days (CR), one progressed at 119 days and went on to another clinical trial (PR), and two died with disease at 212 and 347 days (HI). Non-hematological toxicity was limited to mild injection site skin reaction and fatigue in 77% (10/13) each. No treatment related deaths were observed. The dose and schedule of therapy remained constant in all but three patients: One patient required a 25% dose reduction after cycle 3 followed by another 25% reduction after cycle 11 due to drug induced marrow suppression, one patient required a 25% dose reduction after cycle 2 due to drug induced marrow suppression, and one patient required and tolerated a 25% dose escalation to recapture a CR after cycle 15. CONCLUSION This interim analysis suggests that the administration of subcutaneous azacitidine in an accelerated dosing schedule to elderly patients with acute myelogenous leukemia is a feasible and well-tolerated alternative to standard induction chemotherapy. Disclosures: Benjamin: Celgene Corporation: Research Funding. Off Label Use: Use of azacitidine in AML.. Rossetti:Celgene Corporation: Honoraria, Research Funding, Speakers Bureau. Sahovic:Celgene Corporation: Honoraria, Research Funding, Speakers Bureau. Abdulhaq:Celgene Corporation: Research Funding. Shadduck:Celgene Corporation: Honoraria, Research Funding, Speakers Bureau. Lister:Celgene Corporation: Research Funding.

Azacitidine in the Treatment of Elderly Patients with Acute Myelogenous Leukemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4041-4041 ◽  
Author(s):  
George Labban ◽  
James M. Rossetti ◽  
Richard K. Shadduck ◽  
Entezam Sahovic ◽  
Haifaa Abdulhaq ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Acute Myelogenous Leukemia ◽  
Myelogenous Leukemia ◽  
Open Label ◽  
Open Label Study ◽  
Acute Myelogenous ◽  
Prospective Phase ◽  
Blast Count ◽  
The Mean ◽  
To Receive

Abstract BACKGROUND: Effective treatment of the elderly patient with acute myelogenous leukemia (AML) remains a challenging task. Elderly patients with AML usually respond poorly to standard induction chemotherapy. Response rates in elderly patients are in the range of 30–50% compared to 80–90% in younger patients. Moreover, prolonged hospitalization with treatment related mortality as high as 30% is typical in this older population. In a prior retrospective analysis done at our institution, azacitidine showed an overall response rate of 60% with limited toxicity when administered to patients older than 55 years of age with AML. We present an interim analysis of the first 8 patients enrolled in our prospective, phase II open label study using single agent azacitidine for elderly patients with AML. METHODS: This is a prospective, phase II open label study using azacitidine in patients ≥ 60 years with AML. Inclusion criteria: Newly diagnosed AML (de novo or secondary, WHO criteria) and ECOG ≤ 2. Promyelocytic (M3) phenotype was excluded. Patients with circulating blast count ≥ 30,000/mcl were treated with hydroxyurea until &lt; 30,000/mcl. Azacitidine was given at a dose of 100 mg/m2 subcutaneously for 5 consecutive days every 28 days until disease progression or significant toxicity. G-CSF was given to patients with neutropenia (ANC &lt; 1000/mcl) during all cycles excluding cycle one. RESULTS: Eight patients have been enrolled to date. The mean age of patients is 74 (range: 64–82 years). The mean baseline ECOG performance score was 1 with a mean during treatment of 1. Mean baseline bone marrow blast count was 53% (range: 21–92%). Overall response rate using the NCI response criteria was 75% (6/8): complete response (CR; n=2; 25%) and partial response (PR; n=4; 50%). The mean number of days on treatment was 117 (range: 4–247 days). The mean number of days hospitalized during therapy was 18 (range: 7–51 days) with the majority of therapy being given in the outpatient setting. The mean overall survival time from diagnosis for all patients was 180 days (range: 23–403). The mean overall survival time for responders was 200 days (range: 36–403). Three patients continue on therapy at 146 (PR), 153 (CR) and 247 (PR) days. Of the other responders, one went on to receive an allogeneic PBSCT, one died at 36 days from complications of a strangulated hernia, and one removed himself from study at 82 days (unconfirmed CR) to receive treatment closer to home. All patients were red blood cell (RBC) transfusion dependent at the start of the therapy. To date, two of the six responders (33%) became independent of RBC transfusion. Four patients were transfusion dependent for platelets at the start of therapy with two being non-responders and two achieving a PR. Non-hematological toxicity was limited to mild injection site skin reaction and fatigue in 63% (5/8) each. No treatment related deaths were observed. The dose and schedule of therapy remained constant in all patients except one who required a 25% dose reduction after cycle 3 due to drug induced marrow suppression. CONCLUSION: This interim analysis suggests that the administration of subcutaneous azacitidine in an accelerated dosing schedule to elderly patients with acute myelogenous leukemia is a feasible and well-tolerated alternative to standard induction chemotherapy.

Homoharringtonine Based Triple-Drug Regimen as Induction Chemotherapy for De Novo Acute Myelogenous Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2002-2002
Author(s):  
Jie Jin ◽  
Wenbin Qian ◽  
Hui Liu ◽  
Daozi Jian ◽  
Wenyuan Mai ◽  
...  
Keyword(s):  
Continuous Infusion ◽  
Neutrophil Count ◽  
Acute Myelogenous Leukemia ◽  
De Novo ◽  
Myelogenous Leukemia ◽  
Hematological Toxicity ◽  
Induction Treatment ◽  
Newly Diagnosed ◽  
Acute Myelogenous ◽  
De Novo Aml

Abstract HAA regimen, consisting of homoharringtonine (HHT), aclarubicin and cytarabine (Ara-C), is an efficacious chemotherapy regimen for induction treatment of acute myelogenous leukemia (AML). HHT, a plant alkaloid that is derived from a Chinese evergreen tree, has been shown to inhibit protein, DNA, and RNA synthesis by inhibition of chain initiation. HAA regimen consists of HHT administered at a dose of 4 mg/m2/day by continuous infusion over 4 hours or 2 mg/m2 intramuscular injection twice daily on days 1–3, aclarubicin administered at a dose of 12 mg/m2/day by continuous infusion over 2 hours on days 1–7, and cytarabine (Ara-C) given at a dose of 75 mg/m2 twice daily on days 1–7. Granulocyte colony-stimulating factor (Lenograstim) 5 μg/kg/day subcutaneously was started from the day neutrophil count <0.5×109/l, and continued until the day neutrophil count >1.0×109/l on 3 successive days. For patients with partial remission (PR) after the evaluation of the first course of the therapy, another same induction HAA regimen was administered. Between May 1999 and June 2006, 80 patients consisted of 31 male and 49 female patients were enrolled. All patients had newly diagnosed with de novo AML and had not received any induction treatments before. Out of them, 3 were M1, 44 M2, 2 M4, and 31 M5 according to FAB classification criteria. The median age was 36 (14–59) years. Of all the 76 patients with cytogenetic analysis available, 13 had favorable karyotype, 58 intermediate karyotype, and 5 unfavorable karyotype. In all, 68 (85%) patients achieved complete remission (CR), and the first single course of this induction regimen resulted in a CR rate of 75%. The CR rate of 100%, 88% and 20% were achieved in patients with favorable, intermediate and unfavorable cytogenetics, respectively. We also found that patients with M5 achieved a CR rate of 74% (23/31), while patients with M1 or M2 94% (44/47). The toxicities associated with this regimen were no more than those expected with standard chemotherapy, and the most common non-hematological toxicity was infection. This study suggested that HAA regimen is a safe regimen and it is efficacious, well-tolerable induction therapy for newly diagnosed de novo AML, the use of G-CSF (Lenograstim) appears to be safe, with little risk of accelerating leukemic relapse. A high CR rate can be achieved with only one or two courses of this regimen. Besides, cytogenetics is an important prognostic factor.

Quinine as a multidrug resistance inhibitor: a phase 3 multicentric randomized study in adult de novo acute myelogenous leukemia

Blood ◽  
2003 ◽  
Vol 102 (4) ◽  
pp. 1202-1210 ◽  
Author(s):  
Eric Solary ◽  
Bernard Drenou ◽  
Lydia Campos ◽  
Patricia de Crémoux ◽  
Francine Mugneret ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Multidrug Resistance ◽  
Complete Remission ◽  
Significant Influence ◽  
Acute Myelogenous Leukemia ◽  
De Novo ◽  
Myelogenous Leukemia ◽  
P Glycoprotein ◽  
Acute Myelogenous ◽  
The Mean

Abstract Based on our previous demonstration that quinine could be used clinically to reverse P-glycoprotein–mediated resistance, we designed a multicenter, randomized trial aiming to determine whether quinine would improve the survival of adult patients (15-60 years old) with de novo acute myelogenous leukemia (AML). These patients randomly received (n = 213) or did not receive (n = 212) a 30 mg/kg/day continuous intravenous infusion of quinine in combination with induction chemotherapy combining idarubicine and cytarabine and, depending on bone marrow examination at day 20, an additional course of cytarabine and mitoxantrone. The mean steady-state quinine concentration was 7.8 mg/L and the mean multidrug resistance reversing activity of serum was 1.96. Complete remission (CR) was obtained in 344 patients (80.9%) without significant influence of quinine. Of the patients in complete remission, 82 were assigned to receive HLA-matched bone marrow transplants, whereas 262 were assigned to 2 courses of intensive consolidation chemotherapy, with or without quinine, depending on initial randomization. The 4-year actuarial overall survival (OS) of the 425 eligible patients was 42.0% ± 2.5%, without significant influence of quinine. Of 160 patients who could be studied, 54 demonstrated rhodamine 123 efflux. In these patients, quinine significantly improved the CR rate from 12 of 25 (48.0%) to 24 of 29 (82.8%) (P = .01). However, there was no significant difference in OS. Neither mdr1 gene nor P-glycoprotein expression influenced the outcome. We conclude that quinine does not improve the survival of adult patients with de novo AML, even though it improves CR rate in a small subgroup of patients defined by rhodamine 123 efflux.

Combination Methyltransferase and Histone Deacetylase Inhibition in Elderly Patients with Secondary Acute Myelogenous Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4387-4387 ◽  
Author(s):  
Chandanda Thatikonda ◽  
James M. Rossetti ◽  
Richard K. Shadduck ◽  
John Lister
Keyword(s):  
Elderly Patients ◽  
Histone Deacetylase ◽  
Acute Myelogenous Leukemia ◽  
De Novo ◽  
Symptomatic Relief ◽  
Myelogenous Leukemia ◽  
Platelet Response ◽  
Trisomy 8 ◽  
Secondary Aml ◽  
Acute Myelogenous

Abstract Background: Secondary acute myelogenous leukemia (AML) carries a poor prognosis when compared to de novo AML. Therapeutic options are typically limited as patients are often elderly with comorbidities that preclude intensive chemotherapy. Moreover, resistance to therapy is common. Studies have shown that methyltransferase inhibitors (MTI) have activity in myeloid malignancy. It is not known if addition of histone deacetylase (HDAC) inhibitors improves or prolongs the activity of MTI. We present our experience of 3 elderly patients with secondary AML treated with MTI (azacitidine or decitabine) in combination with an HDAC inhibitor (vorinostat). Methods: Patients include 2 males and 1 female, ages 78 yrs, 82 yrs and 71 yrs. All were initially diagnosed with high-grade myelodysplastic syndrome (MDS), which transformed to CD34+ secondary AML at 33, 14 and 4 months from diagnosis of MDS, respectively. One patient had trisomy 8. Patients received 8, 3 and 4 cycles of MTI before leukemic transformation, respectively. At transformation, one patient failed standard induction therapy and 1 patient failed arsenic trioxide. Both of these patients were then placed back on MTI as maintenance therapy. Vorinostat was added at a dosage of 400 mg daily at MTI cycles 8, 3 and 1 post transformation, respectively. The number of cycles of combination therapy was 6, 9 and 4. Gastrointestinal intolerance was an issue in 2 of these patients: nausea (n=2), diarrhea (n=2), vomiting (n=1) and loss of appetite (n=1). Dose reduction to 100mg in one patient and 300 mg in another resulted in some symptomatic relief. The addition of 5-HT3 antagonists or low dose prednisone allowed dose escalation. One patient had 50% reduction in marrow blasts, 1 had near clearance of the peripheral blasts and 1 had a transient minor platelet response. All 3 patients are alive at 14, 10 and 9 months post transformation (6, 8 and 7 months after addition of vorinostat) with no disease progression, respectively. Conclusion: The combination of MTI and HDAC could be an option in elderly patients with secondary AML without increasing morbidity and mortality. Treatment appears well tolerated when premedication with 5-HT3 antagonists is employed. As the treatment options are limited in high-risk elderly patients with secondary AML, larger studies are needed to investigate the utility of this combination.

A Phase II study of VNP40101M in elderly patients (pts) with de novo poor risk acute myelogenous leukemia (AML)

2008 ◽  
Vol 26 (15_suppl) ◽  
pp. 7026-7026 ◽  
Author(s):  
G. J. Schiller ◽  
D. DeAngelo ◽  
N. Vey ◽  
S. Solomon ◽  
R. Stuart ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Phase Ii ◽  
Acute Myelogenous Leukemia ◽  
De Novo ◽  
Phase Ii Study ◽  
Myelogenous Leukemia ◽  
Poor Risk ◽  
Acute Myelogenous

Effect of fludarabine, cytarabine, filgrastim, and gemtuzumab ozogamicin (FLAG-GO) on relapse-free survival in patients with newly diagnosed core-binding factor acute myelogenous leukemia.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6528-6528
Author(s):  
Gautam Borthakur ◽  
Jorge E. Cortes ◽  
Susan Mary O'Brien ◽  
Tapan M. Kadia ◽  
Zeev Estrov ◽  
...  
Keyword(s):  
Acute Myelogenous Leukemia ◽  
Gemtuzumab Ozogamicin ◽  
Myelogenous Leukemia ◽  
Newly Diagnosed ◽  
Relapse Free Survival ◽  
Core Binding Factor ◽  
Platelet Recovery ◽  
Free Survival ◽  
Binding Factor ◽  
Acute Myelogenous

6528 Background: Prior modulation with fludarabine increases cytarabine-triphosphate (ara-CTP) accumulation and granulocyte-colony-stimulating factor (G-CSF) increases the fludarabine-triphosphate (F-ara-ATP) levels in leukemic blasts. Our front-line regimen of fludarabine, cytarabine and filgrastim (FLAG) based on this rationale showed improved event-free survival compared to anthracycline and cytarabine based regimens in patients (pts) with core-binding factor acute myelogenous leukemia (CBF-AML). Medical Research Council AML 15 trial reported survival benefit from addition of gemtuzumab ozogamicin (GO) to chemotherapy regimens in patients with favorable-risk cytogenetics AML. Methods: In a clinical trial combining GO (3 mg/m2 IV) with FLAG (FLAG-GO) in newly diagnosed CBF-AML, pts received GO on day 1 of induction and of post-remission cycles 2 or 3 and 5 or 6 in addition to FLAG. FLAG regimen was comprised of fludarabine 30 mg/m2 and cytarabine 2 gm/m2 IV daily (both for 5 days in induction and 3-4 days in post-remission cycles) with filgrastim started on day-1 and continued till neutrophil recovery. Pts who received one non-FLAG-GO induction could enroll irrespective of their remission status. Results: Fifty pts [30 with t(8;21) and 20 with Inv16] have been enrolled [5 of 50 (10%) were in remission at enrollment from prior induction]. Median age is 48 years (range, 19-76), median WBC count 12.3 x106/L (range, 1.3-97.2); 12 patients (24%) were >60 years of age and frequency of kit mutation is 8%. Complete remission with or without platelet recovery (CR/CRp) was achieved in 43/45 (96%) pts with 2 deaths in induction. With 6 planned consolidations, the median number of consolidation treatments received is 5 (range, 0-6). Two-thirds of pts needed dose reduction during post-remission cycles. Seven (14%) pts [t(8;21)= 5, Inv 16=2] relapsed and with a median follow-up of 34 months (range, 15-54 months) the relapse-free survival rate is 83%. Conclusions: FLAG-GO is a highly effective regimen and has resulted in high rate of relapse-free survival in pts with newly diagnosed CBF AML.

Sign in / Sign up

Export Citation Format

Share Document