Clofarabine Plus Low-Dose Cytarabine For The Treatment Of Patients Withhigher-Risk Myelodysplastic Syndrome (MDS) Who Have Been Relapsing After, Or Are Refractory To, Hypomethylator Agent Therapy

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1525-1525 ◽  
Author(s):  
Aziz Nazha ◽  
Guillermo Garcia-Manero ◽  
Hagop M. Kantarjian ◽  
Farhad Ravandi ◽  
Gautam Borthakur ◽  
...  
Keyword(s):  
Complete Remission ◽  
Stable Disease ◽  
Low Dose ◽  
Liver Enzymes ◽  
Performance Status ◽  
Single Agent ◽  
Elevated Liver Enzymes ◽  
Elevated Bilirubin ◽  
Low Dose Cytarabine

Abstract Background Treatment with hypomethylating agents (HMA) such as azacitidine and decitabine has changed the overall outcome of patients with MDS. Failure to responed to or relapse from treatment with HMA carries a poor outcome and no approved therapy for these patients exists. Clofarabine is a second generation nucleoside analog with single agent activity in MDS. Aim This is a phase II trial to evaluate the safety and activity of the combination of clofarabine and low dose cytarabine in the treatment of patients with high risk MDS who failed prior HMA therapy. Material and Method Eligible were adults older than 18 years with MDS who have had no response, progressed, or relapsed following at least 4 cycles of therapy with either azacitidine and/or decitabine. Patients were required to have an ECOG performance status of </=2 at the time of study entry. Responses were defined according to IWG 2006 criteria. Induction therapy consisted of clofarabine 15 mg/m2 IV daily X 5 days (days 1-5) and cytarabine 20 mg SC twice daily X 7 days (days 1-7). Patients could receive up to 3 induction cycles as long as they tolerated the therapy and had stable disease. Responding patients proceeded with consolidation therapy with clofarabine 15 mg/m2IV daily X 3 days (days 1-3) and cytarabine 20 mg SC twice daily X 5 days (days 1-5) for a maximum of 12 cycles. Cycles were repeated every 4 to 8 weeks depending on hematopoietic recovery and resolution of toxicities. Results Between January 2012 and March 2013, 29 patients were enrolled. The clinical characteristics are summarized in Table 1. Twenty four patients were evaluable for response (5 patients were too early for response). The overall response rate (ORR) was 50% (8 [33%] achieved complete remission (CR)/ complete remission with incomplete platelets recovery (CRp)/marrow CR, and 4 [17%] had stable disease with hematological improvement). With a median follow up of 4.9 months (range, 1.9-16.7), the median overall survival (OS) was 4.8 months (range, 0.5-13.5). Most toxicities were grade </= 2 and included: elevated liver enzymes in 41% of the patients, elevated bilirubin (38%), rash (28%), nausea (31%), headache (24%), and febrile neutropenia (28%). Grade >/= 3 toxicities included: elevated liver enzymes (3%) and elevated bilirubin (3%). Four-week mortality was 12%. Conclusion The combination of clofarabine and low-dose cytarabine has an ORR of 50% in patients with MDS who failed prior therapy with HMA. The study continues to accrue and updated results with longer follow up will be presented at the meeting. Disclosures: Off Label Use: Clofarabine use in MDS. Faderl:Sanofi-Aventis: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Research Funding.

scholarly journals Clofarabine Plus Low-Dose Cytarabine for the Treatment of Patients with Higher-Risk Myelodysplastic Syndromes (MDS) Who Have Relapsed or Are Refractory to Hypomethylating Agent (HMA) Therapy

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 534-534
Author(s):  
Elias Jabbour ◽  
Koji Sasaki ◽  
Naval Daver ◽  
Naveen Pemmaraju ◽  
Nitin Jain ◽  
...  
Keyword(s):  
High Risk ◽  
Research Funding ◽  
Low Dose ◽  
Liver Enzymes ◽  
Performance Status ◽  
Intermediate Risk ◽  
Elevated Liver Enzymes ◽  
Elevated Bilirubin ◽  
Low Dose Cytarabine

Abstract Background: Treatment with HMAs such as azacitidine and decitabine has changed the overall outcome of patients with MDS. Failure to respond to or relapse from HMA treatment is associated with poor prognosis without further approved therapy. Clofarabine is a second-generation nucleoside analog with single-agent activity in MDS. Aim: This is a phase II trial to evaluate the safety and activity of the combination of clofarabine and low-dose cytarabine in the treatment of patients with high-risk MDS who failed prior HMA therapy. Materials and Methods: Eligible patients were adults older than 18 years with MDS who had no response, progressed, or relapsed following at least 4 cycles of therapy with either azacitidine and/or decitabine and an ECOG performance status of ≤ 2 at the time of study entry. Responses were defined according to IWG 2006 criteria. Induction therapy consisted of clofarabine 15 mg/m2 IV daily for 5 days (days 1-5) and cytarabine 20 mg SC twice daily for 7 days (days 1-7). Responding patients proceeded with consolidation therapy with clofarabine 15 mg/m2 IV daily for 3 days (days 1-3) and cytarabine 20 mg SC twice daily for 5 days (days 1-5) every 4 weeks for a maximum of 12 cycles. Overall survival (OS) was defined as the time between the date of the first dose of clofarabine and the date of death from any cause. Univariate (UVA) and multivariate analysis (MVA) related to response and survival were performed with Cox regression analysis. Results: Between January 2012 and December 2013, 56 patients were enrolled. Fifty-two patients were evaluable for response (4 patients had not been on-study long enough to evaluate). The median follow-up is 15.3 months (range, 1.2-27.7+), and the median age at enrollment was 71 years (31-83). Ten patients (19%) had prior chemotherapy and 12 (23%) had prior radiation therapy. Median bone marrow blast percentage was 15% (6-30%). Three patients (6%) had CMML-1, 4 (8%) had CMML-2, 7 (14%) had RAEB-1, 19 (37%) had RAEB-2, and 19 (37%) had RAEB-T. Eight (15%) patients had intermediate-1 risk, 23 (44%) had intermediate-2 risk, and 21 (40%) had poor risk by IPSS. By IPSS cytogenetic risk, 25 patients (48%) had low-risk cytogenetics, 15 (29%) had intermediate-risk, and 12 (23%) had high-risk. Mutational analysis detected 2 (4%) FLT3-ITD, 0 FLT3-D835, 7 (13%) RAS, 2 (4%) NPM1, and 2 (4%) JAK2 mutations. Thirty-nine patients (75%) received prior azacitidine therapy and 15 (29%) received prior decitabine therapy. The overall response rate (ORR) was 48% (9 [17%] achieved complete remission [CR], 3 [6%] complete remission with incomplete platelet recovery [CRp], 7 [13%] marrow CR, and 6 [12%] had stable disease with hematological improvement), and median duration of response was 12.0 months (range, 2.0-26.7+). Five patients (10%) went on to receive allogeneic stem cell transplantation. Of the 25 patients with low-risk cytogenetics, 16 (64%) achieved OIR, 5 (20%) CR, 3 (12%) CRp, 6 (24%) mCR, and 2 (8%) HI. Of the 15 patients with intermediate-risk cytogenetics, 5 (33%) had OIR, 4 (27%) CR, and 1 (4%) mCR. Of 12 patients with high-risk cytogenetics, 2 (17%) had OIR, 1 (8%), CR, and 1 (8%) HI. Median OS was 6.8 months (range, 0.4-27.7+). The median OS in patients with response and those without response was >12.4 months (range, 3.5-27.7+) and 3.4 months (range, 0.4-16.1), respectively. Most toxicities were of grade ≤ 2 and included elevated liver enzymes in 41% of patients, elevated bilirubin in 38%, rash in 28%, nausea in 31%, headache in 24%, and febrile neutropenia in 28%. Grade ≥ 3 toxicities included elevated liver enzymes (3%) and elevated bilirubin (3%). 21 (40%) patients had clofarabine dose reduction after a median of 2 courses (range, 1-8). UVA and MVA for survival identified performance status ≥2 (p=0.002; HR, 4.860; 95%CI, 1.784-13.244), stable disease or progressive disease after clofarabine (p<0.001; HR, 8.372; 95%CI, 3.233-21.677), thrombocytopenia <30 (/109L) (p=0.001; HR, 3.659; 95%CI 1.682-7.958), and complex cytogenetics (UVA, p<0.001; MVA, p= 0.110, HR, 2.329; 95%CI 0.826-6.564) as prognostic factors for poorer OS. Conclusion: The combination of clofarabine and low-dose cytarabine has an ORR of 48% in patients with MDS who failed prior therapy with HMA. The study continues to accrue, and updated results with longer follow up will be presented at the meeting. Disclosures Daver: Novartis: Research Funding. Kadia:GSK: Research Funding; ARIAD: Honoraria. Borthakur:Tetralogic Pharmaceuticals: Research Funding. O'Brien:Amgen, Celgene, GSK: Consultancy; CLL Global Research Foundation: Membership on an entity's Board of Directors or advisory committees; Emergent, Genentech, Gilead, Infinity, Pharmacyclics, Spectrum: Consultancy, Research Funding; MorphoSys, Acerta, TG Therapeutics: Research Funding. Kantarjian:ARIAD: Research Funding; Pfizer: Research Funding; Amgen: Research Funding. Garcia-Manero:Epizyme, Inc: Research Funding.

Clofarabine Plus Low-Dose Cytarabine Induction Followed by Consolidation with Clofarabine Plus Low-Dose Cytarabine Alternating with Decitabine as Frontline Therapy for Patients (pts) with Acute Myeloid Leukemia (AML) ≥ 60 Years (yrs).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2058-2058
Author(s):  
Sameer A Parikh ◽  
Hagop Kantarjian ◽  
Guillermo Garcia-Manero ◽  
Elias Jabbour ◽  
Tapan Kadia ◽  
...  
Keyword(s):  
Induction Therapy ◽  
Research Funding ◽  
Low Dose ◽  
Single Agent ◽  
Disease Free Survival ◽  
Response Rates ◽  
High Response ◽  
Multiple Drugs ◽  
Low Dose Cytarabine

Abstract Abstract 2058 Poster Board II-35 Therapy of AML for elderly pts (≥ 60 yrs) remains challenging with low response rates, short durability of responses, and high toxicity rates following conventional therapy with standard-dose ara-C/anthracycline combinations. Clofarabine is a novel deoxyadenosine nucleoside analogue with single agent activity in frontline AML for older pts with ≥ 1 unfavorable prognostic factors. We have recently reported results of a randomized study suggesting higher response rates and comparable safety profile with the combination of clofarabine plus low-dose cytarabine over clofarabine alone. We have designed the current study of clofarabine plus low-dose cytarabine induction followed by consolidation with clofarabine plus low-dose cytarabine alternating with decitabine to maintain high response rates and improve disease-free survival based on the following hypotheses: 1) to extend duration of therapy by administering lower doses of the agents; and 2) to provide multiple drugs with different mechanisms of action to decrease risk of resistance. Pts were eligible if ≥ 60 yrs of age with newly diagnosed AML. Pts were excluded for ECOG PS > 2, creatinine > 1.5 mg/dL, cardiac ejection fraction < 40%, and prior therapy with clofarabine or decitabine. Induction therapy consisted of clofarabine 20mg/m2 i.v daily × 5 days plus cytarabine 20mg s.c. twice daily × 10 days in a laminar air flow room. Responding pts could receive up to 17 courses of consolidation therapy of clofarabine plus cytarabine (over 3 and 7 days, respectively) during consolidation courses 1-2, 6-8, 12-14) alternating with decitabine 20mg/m2 i.v. daily for 5 days during courses 3-5, 9-11, and 15-17. All pts received antibiotic prophylaxis with levofloxacin, valacyclovir and itraconazole (or equivalent). Forty pts have been enrolled with a median age of 70 yrs (range 60-80) of whom 22 (55%) had secondary AML (antecedent hematologic disorder in 11 pts). Two pts had received previous azacitidine for MDS. Fourteen pts (35%) had abnormal cytogenetics of whom 10 (25%) had monosomy 5, 7, or both. Four patients (10%) had a FLT3/ITD mutation. Of the 34 pts evaluable for response, 20 (59%) achieved CR and 2 (6%) CRp for an OR rate of 65%. Only 2 pts required 2 courses to CR. The OR rate for patients with diploid versus abnormal cytogenetics was 80% vs 50%; for pts with prior MDS versus no prior MDS 76% and 50%; and 75% for patients with FLT3 mutation. The median time to CR/CRp was 38 days (range 27-103). With a median follow up of 3.5 months (range 0.7-8.1), 2 pts relapsed (CR duration of 3.3 and 4.2 months, respectively); responses are ongoing in the remainder. Three pts (9%) died during induction therapy (one during re-induction) before a response could be established. The median number of consolidation cycles received by pts in CR was 3 (range 1-5). Most toxicities were ≤ grade 2 and included nausea/vomiting, diarrhea, rash, headache and mucositis. Six pts developed grade 3 elevations in serum transaminases which resolved at the end of induction therapy. Myelosuppression and neutropenic fever were common, but prolonged myelosuppression was rare. In conclusion, clofarabine plus low-dose cytarabine achieves high response rates with a manageable toxicity profile and low induction mortality in elderly pts with previously untreated AML. Time-to-event parameters will be provided with more extensive follow up. Disclosures: Off Label Use: Clofarabine and Decitabine in AML. Kantarjian:Genzyme: Consultancy, Research Funding. Faderl:Genzyme: Consultancy, Research Funding; Eisai: Research Funding, Speakers Bureau.

Economic Impact of Disease Progression In Follicular Non-Hodgkin's Lymphoma.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1522-1522
Author(s):  
Sacha-Satram Hoang ◽  
Stephen Gruschkus ◽  
Joseph Darragh ◽  
Michael Forsyth ◽  
Roy Beveridge ◽  
...  
Keyword(s):  
Complete Remission ◽  
Lymph Nodes ◽  
Disease Progression ◽  
Stable Disease ◽  
Performance Status ◽  
Cost Of Care ◽  
Ecog Performance Status ◽  
Physician Visits ◽  
Outpatient Physician

Abstract Abstract 1522 Background: Follicular NHL (f-NHL) accounts for approximately 70% of indolent lymphomas. We estimated the marginal cost of progression for patients with f-NHL treated in the outpatient community setting. Methods: Using US Oncology's iKnowMed electronic medical records (EMR), we identified 1002 f-NHL patients who achieved complete remission or had documented stable disease between 7/1/2006 and 2/29/2008. This database captures information in a network of about 1,200 community-based oncologists where patients are treated according to usual clinical practice with no criteria for therapy selection and no schedule of visits imposed. To estimate outpatient cost of care, we linked the EMR data to US Oncology's claims data warehouse. Patients were categorized into 2 cohorts based on whether they experienced disease progression or not. Patient demographic and clinical information were characterized at baseline and follow-up time was censored at the last entry for disease status or 6 months after date of complete remission/ stable disease or date of progression. Costs per patient month (estimated based on outpatient claims and normalized to 2007 Medicare reimbursement rates) were compared between progressed and non-progressed patients. Econometric regression analysis was used to compare healthcare cost after adjusting for potential confounders. To further explore the economic burden of progression, we compared resource utilization as measured by outpatient physician visits, chemotherapy visits, laboratory and acute care visits. Results: Of the 1,002 f-NHL patients identified, 204 progressed and 798 did not. At baseline, patients who progressed were more likely to have been diagnosed with advanced disease, have 4+ positive lymph nodes, have worse ECOG performance status and high LDH and low HGB levels compared to patients who did not progress. The mean overall costs per patient-month over the 6-month follow-up period were significantly higher for patients who progressed vs. those who did not progress ($3612 vs. $965; difference = $2,647; p<0.001), with a relative cost nearly 4 times higher. After adjusting for differences in clinical factors (HGB levels, lymph nodes, ECOG performance status), disease progression was associated with a 2-fold increased cost (p<0.001). Patients who progressed had significantly higher frequencies of outpatient physician visits and laboratory procedures compared to patients without progression and were significantly more likely to receive chemotherapy and be admitted to the hospital and/or ER. Conclusions: Results of this retrospective study indicate that therapies which delay disease progression for f-NHL may provide substantial economic benefits in addition to improvements in clinical outcomes. Disclosures: Hoang: Genentech: Consultancy. Gruschkus:US Oncology: Employment. Darragh:US Oncology: Employment. Forsyth:US Oncology: Employment. Beveridge:US Oncology: Consultancy, Employment. Reyes:Genentech Inc: Employment.

scholarly journals Clofarabine Plus Low-Dose Cytarabine for the Treatment of Patients with Higher-Risk Myelodysplastic Syndrome (MDS) Who Have Been Relapsing after, or Are Refractory to, Hypomethylating Agent (HMA) Therapy

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3166-3166 ◽  
Author(s):  
Elias J. Jabbour ◽  
Hagop M. Kantarjian ◽  
Koji Sasaki ◽  
Tapan M. Kadia ◽  
Farhad Ravandi ◽  
...  
Keyword(s):  
Research Funding ◽  
Low Dose ◽  
Group Performance ◽  
Performance Status ◽  
Advisory Board ◽  
Cell Transplant ◽  
Complex Karyotype ◽  
Overall Response ◽  
Low Dose Cytarabine

Abstract Background: HMA therapy is standard of care for patients with MDS. Outcome post HMA failure is poor with a median survival of 4-6 months. Clofarabine is a second generation nucleoside analog with single agent activity in MDS. The objective of this phase II trial is to evaluate the safety and activity of the combination of clofarabine and low dose cytarabine in the treatment of patients with high risk MDS who failed prior HMA therapy. Methods: Eligible patients were adults older than 18 years with MDS intermediate-1 and higher by the IPSS, who have had no response, progressed, or relapsed following at least 4 cycles of therapy with either azacitidine and/or decitabine. Patients were required to have an Eastern Cooperative Oncology Group performance status of </=2 at the time of study entry. Responses were defined according to International Working Group 2006 criteria. Induction therapy consisted of clofarabine 10-15 mg/m2 IV daily X 5 days (days 1-5) and cytarabine 20 mg SC twice daily X 7 days (days 1-7). Patients could receive up to 3 induction cycles as long as they tolerated the therapy and had stable disease. Responding patients proceeded with consolidation therapy with clofarabine 10-15 mg/m2IV daily X 3 days (days 1-3) and cytarabine 20 mg SC twice daily X 5 days (days 1-5) for a maximum of 12 cycles. Cycles were repeated every 4 to 8 weeks depending on hematopoietic recovery and resolution of toxicities. Results: From January 2012 to August 2015, 80 eligible patients were enrolled in this prospective study (NCT01444742) and received a median of 2 cycles (range, 1-12) (Table 1). The overall response rate (ORR) was 46% (16 [20%] achieved complete remission (CR), 17 [21%] marrow CR, 1 [1%] partial response (PR), 3 [4%] hematological improvement (HI)) with a median response duration of 7 months. The median time to response was 42 days (range, 9-191). By multivariate analysis, complex karyotype was the only independent factor predicting for response (hazard ratio [HR] 0.13; 95% confidence interval [CI]: 0.03- 0.62; p=0.01). Of the 37 patients with diploid karyotype, the overall response was 68% (7 [19%] achieved CR, 15 [41%] marrow CR, 1 [3%] PR, 3 [4%] HI). Nine of the responding patients received subsequent allogeneic stem cell transplant (ASCT). With a median follow-up of 24 months (range: 1-51 months), the median event-free survival (EFS) and overall survival (OS) times were 5 months (95% CI: 2.7-6.3) and 11 months (95% CI: 6.5-14.9), respectively (Figure 1). The median OS for responding and non-responding patients was 24 months (95% CI: 11.7-35.6) and 5 months (95% CI: 2.8-6.2), respectively (p<0.001). There was no difference in OS whether patients were censored or not at the time of ASCT (p=0.463). At last follow-up, 22 patients (28%) remained alive: 1 is receiving low-dose clofarabine and cytarabine, 5 are alive in response after ASCT, 9 are receiving salvage therapy, 1 went to hospice, and 6 were lost to follow-up. By multivariate analyses, complex karyotype, platelet count less than 30 x 109/L, and poor performance status were independently associated with poor survival. In addition, the response to the combination of low-dose clofarabine and cytarabine was independently associated with better OS (HR 0.17; 95% CI 0.09-0.36; p<0.001). Grade ≥ 3 therapy-related toxicity included infections (34%), increased liver functional tests (8%), acute renal failure (3%), skin rash (3%), syncope (1%), and rectal bleeding (1%). Twenty-two (28%) patients had clofarabine dose reduction after a median of 2 courses. After 47 patients were enrolled and several patients experienced infections during induction, the protocol was amended to reduce the dose of clofarabine to 10 mg/m2 per day for 5 and 3 days during the induction and consolidation phases, respectively. There was no difference in responses before and after the modification to the protocol's dosing schedule (p=0.314). Conclusion: The combination of low-dose clofarabine and cytarabine in patients with higher-risk MDS after HMA failure resulted in an ORR of 46% and median OS of 11 months and may be particularly effective in patients with diploid karyotype. Our results also indicate that the combination of low-dose clofarabine and cytarabine may be useful as a bridge to ASCT in eligible patients. Disclosures Jabbour: ARIAD: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Research Funding; BMS: Consultancy. Cortes:ARIAD: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Teva: Research Funding. Jain:Abbvie: Research Funding; Infinity: Research Funding; Servier: Consultancy, Honoraria; Incyte: Research Funding; Genentech: Research Funding; Pharmacyclics: Consultancy, Honoraria, Research Funding; ADC Therapeutics: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Research Funding; Celgene: Research Funding; Seattle Genetics: Research Funding; Novimmune: Consultancy, Honoraria; BMS: Research Funding. DiNardo:Agios: Other: advisory board, Research Funding; Daiichi Sankyo: Other: advisory board, Research Funding; Novartis: Other: advisory board, Research Funding; Abbvie: Research Funding; Celgene: Research Funding. Konopleva:Cellectis: Research Funding; Calithera: Research Funding.

Clofarabine Plus Low-Dose Cytarabine Induction Followed By Clofarabine Plus Low-Dose Cytarabine Alternating With Decitabine Consolidation In Acute Myeloid Leukemia Frontline Therapy For Older Patients

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3948-3948
Author(s):  
Aziz Nazha ◽  
Hagop M. Kantarjian ◽  
Farhad Ravandi ◽  
Xuelin Huang ◽  
Xuemei Wang ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Single Agent ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Elevated Creatinine ◽  
Prolonged Consolidation ◽  
Low Dose Cytarabine

Abstract Background The outcome of elderly patients (pts) with acute myeloid leukemia (AML) treated with currently available therapies remains unsatisfactory. Clofarabine has single agent activity in AML. The combination of clofarabine with low-dose cytarabine produced higher response rates with a comparable safety profile compared with single-agent clofarabine. We previously reported a phase II study of clofarabine + low dose cytarabine followed by prolonged consolidation with clorarabine + low dose cytarabine alternating with decitabine in elderly patients with newly diagnosed AML (Faderl, Cancer 2012). The complete remission (CR) rate was 58%. With median follow up of 31.2 months, the median overall survival (OS) was 12.7 months, and the median relapse free survival was 14.1months. The combination was well tolerated with induction mortality of 3% (Early Death <28 Days), 7% at 8-weeks. Here we report the result with a larger patient population and longer follow up. Material and Methods Pts were eligible if they were >/= 60 years of age with newly diagnosed AML (based on World Health Organization [WHO] criteria) or high-risk myelodysplastic syndrome (MDS; >/=10% blasts or >/= intermediate-2 by the International Prognostic Scoring System) with Eastern Cooperative Oncology Group (ECOG) performance status of </= 2 and adequate organ function (serum total bilirubin </=2 mg/dL, alanine aminotransferase or aspartate aminotransferase </= 4 X the upper limit of normal, serum creatinine </= 2 mg/dL, and cardiac ejection fraction >40%). Induction therapy consisted of clofarabine 20 mg/m2 IV daily X 5 days (1-5) plus cytarabine 20 mg subcutaneously (SC) twice daily (BID) X10 days (1-10). All responses were defined as per IWG criteria (2003). Pts who did not achieve a CR could receive 1 re-induction cycle at the same dose after at least 28 days from C #1. Pts could receive up to 17 cycles of consolidation therapy. Consolidation was administered in blocks of 3 cycles where clofarabine 20 mg/m2 IV daily X 3 days (1-3) plus cytarabine 20 mg SC BID X 7 days (1-7) alternated with decitabine 20 mg/m2IV X5 days (1-5). Consolidation cycles were repeated every 4 to 7 weeks depending on hematopoietic recovery. Results Between 10/21/08 and 10/17/2011, a total of 118 patients were enrolled. The clinical characteristics are summarized in Table 1. The overall response rate (ORR) was 68% (71 [60%] CR, 9 [8%] CRp/CRi). Twenty two (19%) pts required re-induction, 16 (73%) achieved a response (12 achieved CR, 2 CRp, and 2 CRi). Median number of cycles received was 3 (range, 1-19). With median follow up of 31.2 months (range, 9.5-53.9), the median OS was 11.1 (range, 0.2-53.9), EFS 7.7 (range, 0.2-49.5), and relapse-free survival (RFS) 15.9 months (range, 0.3-48.3). The median OS among the responders was 21.1 months (range, 1.3-53.9). Four-week mortality was 3% and 8-week mortality 8%. Adverse events were predominantly grade 2 or less and included (>/= 10%): elevated liver enzymes (53%), elevated bilirubin (42%), diarrhea (19%), nausea (81%), rash (54%), hand and foot syndrome (10%), and elevated creatinine (10%). Grade 3 or more toxicities included: elevated creatinine (3%), rash (2%), vomiting (1%), and hand and foot syndrome (1%). No unexpected toxicities were observed. Conclusion Clofarabine plus low-dose cytarabine followed by prolonged consolidation alternating with decitabine is an active regimen with an ORR of 73% in older patients with newly diagnosed AML and high risk MDS. The regimen was well tolerated with low induction mortality. A randomized trail to compare this combination to best available therapy is needed to further asses the role of this combination in the treatment paradigm of elderly patients with AML. Disclosures: Off Label Use: Clofarabine and decitabine use in AML. Faderl:Sanofi-Aventis: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Research Funding.

scholarly journals Gestational trophoblastic neoplasia: A 6 year retrospective study

2014 ◽  
Vol 03 (01) ◽  
pp. 033-037 ◽  
Author(s):  
Sushruta Shrivastava ◽  
Amal Chandra Kataki ◽  
Debabrata Barmon ◽  
Pankaj Deka ◽  
Chidananda Bhuyan ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Complete Remission ◽  
Risk Score ◽  
Single Agent ◽  
Response To Treatment ◽  
Gestational Trophoblastic Neoplasia ◽  
Response To Chemotherapy ◽  
Chemotherapy Patients ◽  
Line Chemotherapy

Abstract Aims and Objectives: To study the clinical presentations of gestational trophoblastic neoplasia and its response to chemotherapy. Materials and Methods: This is a retrospective study of 28 women of gestational trophoblastic neoplasia evaluated over a period of 6 years from January 2004 to December 2009. Patients were evaluated on the basis of their age, number of deliveries, history of abortion or molar pregnancy, and the treatment received. All patients were scored on the basis of WHO scoring system. Patients with low risk (score </=6) received single agent chemotherapy with methotrexate or actinomycin D. Patients with high risk (score >/=7) received multiple agent chemotherapy with EMACO regimen. After completion of chemotherapy patients were followed for a minimum of 2 years. The response to treatment was evaluated during follow-up by clinical examination, beta hCG levels and imaging as and when required. Results: Out of 28 women only 27 could be evaluated, because 1 patient was lost to follow-up. Out of 27 patients, 18 patients (66.67%) achieved complete remission with the first-line chemotherapy and additional 25.92% (7/27) achieved complete remission with second line chemotherapy resulting in complete remission of 92.5% (25/27). Conclusion: Gestational trophoblastic neoplasia is curable if patient is properly evaluated and scored. It shows good response to chemotherapy.

Long-term follow-up of a phase III intergroup study of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: a cooperative group study.

1997 ◽  
Vol 15 (7) ◽  
pp. 2564-2569 ◽  
Author(s):  
S B Saxman ◽  
K J Propert ◽  
L H Einhorn ◽  
E D Crawford ◽  
I Tannock ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Combination Chemotherapy ◽  
Performance Status ◽  
Single Agent ◽  
Phase Iii ◽  
Long Term Follow Up ◽  
Intergroup Trial ◽  
Advanced Urothelial Carcinoma

PURPOSE A previously reported randomized intergroup trial demonstrated that combination chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) was superior to single-agent cisplatin in patients with advanced urothelial carcinoma. We conducted a long-term analysis of patients included in the intergroup trial to examine factors associated with long-term survival. PATIENTS AND METHODS Two-hundred fifty-five assessable patients with urothelial carcinoma were randomized to receive either single-agent cisplatin (70 mg/m2 on day 1) or combination chemotherapy with methotrexate (30 mg/m2 on days 1, 15, and 22), vinblastine (3 mg/m2 on days 2, 15, and 22), doxorubicin (30 mg/m2 on day 2), and cisplatin (70 mg/m2 on day 2). Courses were repeated every 28 days. The association between patient characteristics and survival was assessed using Cox proportional hazards models. RESULTS With long-term follow-up evaluation, survival in the M-VAC arm continues to be superior to cisplatin (P = .00015, log-rank test). Predictors of survival include performance status, histology, and the presence of liver or bone metastasis. Only 3.7% of the patients randomized to M-VAC are alive and continuously disease-free at 6 years. CONCLUSION Long-term follow-up evaluation of the intergroup trial confirms that M-VAC is superior to single-agent cisplatin in patients with advanced urothelial carcinoma; however, durable progression-free survival is rare. Patients with non-transitional-cell histology, poor performance status, and/or bone or visceral involvement fare poorly and are unlikely to benefit significantly from M-VAC chemotherapy.

Maintenance with low-dose cytarabine for acute myeloid leukemia in complete remission

1992 ◽  
Vol 65 (2) ◽  
pp. 71-74 ◽  
Author(s):  
E. Archimbaud ◽  
B. Anglaret ◽  
X. Thomas ◽  
J. Jaubert ◽  
C. Sebban ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Low Dose Cytarabine ◽  
Acute Myeloid

A Retrospective Comparison of Matched Elderly Patients Treated with Laromustine (Cloretazine®) or Best Supportive Care or Low Dose Ara-C in the LRF AML14 Trial

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2960-2960 ◽  
Author(s):  
Robert Hills ◽  
Susan O’Brien ◽  
Verena Karsten ◽  
Alan K. Burnett ◽  
Francis Giles
Keyword(s):  
High Risk ◽  
Supportive Care ◽  
Low Dose ◽  
De Novo ◽  
Performance Status ◽  
Single Agent ◽  
Best Supportive Care ◽  
Cell Counts ◽  
Retrospective Comparison ◽  
De Novo Aml

Abstract Background : A substantial proportion of older patients with AML are considered unlikely to benefit from an intensive treatment approach. They often receive either best supportive care (BSC), low dose treatment such as Low Dose Ara-C (LDAC), or clinical trials of novel agents. In one of the few randomised studies where patients were prospectively considered likely to be unfit for intensive therapy, LDAC was superior to BSC with 18% v 1% patients achieving CR. No patients with high risk cytogenetics (Grimwade 1998), achieved CR (Burnett 2007). Laromustine (Cloretazine®) is a novel sulfonylhydrazine alkylating agent which preferentially targets the O6 position of guanine resulting in DNA cross-links. Laromustine has previously shown clinical activity in patients with de novo AML and high risk MDS (Giles et al. JCO 2007). A confirmatory phase II study of single agent laromustine was conducted in previously untreated patients ≥ 60 years old with de novo AML, prospectively considered likely to be unfit for intensive chemotherapy. Patients had at least one poor risk factor, defined by age ≥70, performance status 2, unfavorable cytogenetics, or cardiac, pulmonary or hepatic dysfunction. Eighty-five patients received induction therapy with 600 mg/m2 laromustine. Second induction cycles were administered in 14 patients after partial response or hematologic improvement. Eighteen patients received at least one consolidation cycle of cytarabine 400 mg/m2/day CIV for 5 days. Methods: A retrospective non-randomised comparison was performed between the 85 patients treated with laromustine, and 121 patients satisfying the same entry criteria, treated in the AML 14 trial with either BSC or LDAC. Outcomes were compared using Mantel-Haenszel and logrank methods for unadjusted comparisons, and regression methods for adjusted analyses. Results : Patients in AML14 were slightly older than those treated with laromustine (median age 75 v 73), and tended to have higher white blood cell counts; by contrast, there were significantly fewer cardiac or respiratory comorbidities reported in the AML14 population. Other important risk factors such as performance status and cytogenetics were similar between the groups. Responses overall (CR/CRp) were seen in 33% (28/85) of patients treated with laromustine, compared with 2% (1/60) and 23% (14/61) in patients treated with BSC and LDAC (p&lt;0.0001, p=0.2, respectively). In particular, 1 patient with −5/del(5q), and 3 patients with −7/del(7q) cytogenetics experienced a CR with laromustine; patients in AML 14 with adverse cytogenetics saw no remissions. Survival was significantly improved in the laromustine group compared to BSC (1 year survival 20% v 8%, unadjusted HR 0.58 [0.40–0.84] p=0.004), and roughly comparable to that of LDAC (1 year survival 20% v 25%, HR 1.04 [0.73–1.49] p=0.8). Analyses adjusted for differences in baseline demographics, and using propensity scores gave consistent figures. Conclusions: Retrospective comparison of unrandomised data has significant limitations even though care has been taken to match for factors known to be predictive for survival. Laromustine was able to achieve a higher CR rate than LDAC or BSC, and produced remissions in groups where no remissions have previously been seen with LDAC or BSC. Laromustine gave significantly better survival than BSC, and demonstrated similar survival to LDAC.

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