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Richard A Larson - One of the best experts on this subject based on the ideXlab platform.

  • Final results of EFC6663: a multicenter, international, phase 2 study of alvocidib for patients with Fludarabine-refractory chronic lymphocytic leukemia.
    Leukemia research, 2015
    Co-Authors: Mark C. Lanasa, Thomas J Kipps, Richard A Larson, Leslie A. Andritsos, Jennifer R. Brown, Janice L. Gabrilove, Federico Caligaris-cappio, Paolo Ghia, Véronique Leblond, Donald Milligan
    Abstract:

    Early phase studies of alvocidib showed activity in relapsed CLL including patients with high risk genomic features and those refractory to Fludarabine. A multi-center, international, phase II study of alvocidib in Fludarabine refractory CLL was undertaken to validate these early results. Patients with Fludarabine refractory CLL or prolymphocytic leukemia arising from CLL were treated with single agent alvocidib. The primary outcome measure was overall response rate, with secondary outcomes including survival, toxicity, and response duration. One hundred and sixty five patients were enrolled and 159 patients were treated. The median age was 61 years, the median number of prior therapies was 4, and 96% of patients were Fludarabine refractory. The investigator-assessed overall response rate was 25%; the majority of responses were partial. Response rates were lower among patients with del(17p) (14%), but equivalent in patients with del(11q) or bulky lymphadenopathy. Median progression free and overall survival were 7.6 and 14.6 months, respectively. Tumor lysis occurred in 39 patients (25%), and 13 received hemodialysis. Diarrhea, fatigue, and hematologic toxicities were common. Alvocidib has clinical activity in patients with advanced, Fludarabine refractory CLL. Future studies should focus on discovery of biomarkers of clinical response and tumor lysis, and enhanced supportive care measures.

  • phase iii trial of Fludarabine plus cyclophosphamide compared with Fludarabine for patients with previously untreated chronic lymphocytic leukemia us intergroup trial e2997
    Journal of Clinical Oncology, 2007
    Co-Authors: Ian W Flinn, Frederick R Appelbaum, Richard A Larson, Donna Neuberg, Michael R Grever, Gordon W Dewald, John M Bennett, Elisabeth Paietta, Mohamad A Hussein, Dennis F Moore
    Abstract:

    Purpose The combination of Fludarabine and cyclophosphamide is an effective regimen for patients with chronic lymphocytic leukemia (CLL). However, it may be accompanied by increased toxicity compared with Fludarabine alone. E2997 is a phase III randomized Intergroup trial comparing Fludarabine and cyclophosphamide (FC arm) versus Fludarabine (F arm) alone in patients receiving their first chemotherapy regimen for CLL. Patients and Methods Symptomatic, previously untreated patients with CLL were randomly assigned to receive either Fludarabine 25 mg/m2 intravenously (IV) days 1 through 5 or cyclophosphamide 600 mg/m2 IV day 1 and Fludarabine 20 mg/m2 IV days 1 through 5. These cycles were repeated every 28 days for a maximum of six cycles. Results A total of 278 patients were randomly assigned in this Intergroup study. Treatment with Fludarabine and cyclophosphamide was associated with a significantly higher complete response (CR) rate (23.4% v 4.6%; P < .001) and a higher overall response (OR) rate (74.3% ...

  • addition of rituximab to Fludarabine may prolong progression free survival and overall survival in patients with previously untreated chronic lymphocytic leukemia an updated retrospective comparative analysis of calgb 9712 and calgb 9011
    Blood, 2005
    Co-Authors: John C Byrd, Bercedis L Peterson, Frederick R Appelbaum, Jonathan E Kolitz, Lois E Shepherd, John D Hines, Vicki A Morrison, Charles A Schiffer, Richard A Larson
    Abstract:

    Fludarabine and rituximab combination therapies in chronic lymphocytic leukemia (CLL) have yielded promising early results, but no comparative efficacy data relative to standard Fludarabine treatment regimens have been reported. To assess the effect of the addition of rituximab to Fludarabine therapy, we retrospectively compared the treatment outcome of patients with similar clinical characteristics enrolled on 2 multicenter clinical trials performed by the Cancer and Leukemia Group B and the US Intergroup that used Fludarabine and rituximab (CALGB 9712, n = 104) or Fludarabine (CALGB 9011, n = 178). In multivariate analyses controlling for pretreatment characteristics, the patients receiving Fludarabine and rituximab had a significantly better progression-free survival (PFS; P < .0001) and overall survival (OS; P = .0006) than patients receiving Fludarabine therapy. Two-year PFS probabilities were 0.67 versus 0.45, and 2-year OS probabilities were 0.93 versus 0.81. Infectious toxicity was similar between the 2 treatment approaches. These comparative data are retrospective and could be confounded by differences in supportive care or dissimilar enrollment of genetic subsets on each trial. Confirmation of these findings will require a prospective randomized trial comparing Fludarabine and rituximab to Fludarabine.

  • therapy related myeloid leukemias are observed in patients with chronic lymphocytic leukemia after treatment with Fludarabine and chlorambucil results of an intergroup study cancer and leukemia group b 9011
    Journal of Clinical Oncology, 2002
    Co-Authors: Vicki A Morrison, Kanti R Rai, Bercedis L Peterson, Frederick R Appelbaum, Jonathan E Kolitz, Laurence Elias, John D Hines, Richard A Larson, Lois Shepherd, Charles A Schiffer
    Abstract:

    PURPOSE: Patients with chronic lymphocytic leukemia (CLL) may have disease transformation to non-Hodgkin’s lymphoma or prolymphocytic leukemia; however, development of therapy-related acute myeloid leukemia (t-AML) is unusual. A series of patients enrolled onto an intergroup CLL trial were examined for this complication. PATIENTS AND METHODS: A total of 544 previously untreated B-cell CLL patients were enrolled onto a randomized intergroup study comparing treatment with chlorambucil, Fludarabine, or Fludarabine plus chlorambucil. Case report forms from 521 patients were reviewed for t-AML. RESULTS: With a median follow-up of 4.2 years, six patients (1.2%) to date have developed therapy-related myelodysplastic syndrome (t-MDS; n = 3), t-AML (n = 2), or t-MDS evolving to t-AML (n = 1), from 27 to 53 months (median, 34 months) after study entry. This included five (3.5%) of 142 patients treated with Fludarabine plus chlorambucil and one (0.5%) of 188 receiving Fludarabine; no chlorambucil-treated patients de...

  • impact of therapy with chlorambucil Fludarabine or Fludarabine plus chlorambucil on infections in patients with chronic lymphocytic leukemia intergroup study cancer and leukemia group b 9011
    Journal of Clinical Oncology, 2001
    Co-Authors: Vicki A Morrison, Kanti R Rai, Bercedis L Peterson, Frederick R Appelbaum, Jonathan E Kolitz, Laurence Elias, Lois E Shepherd, John D Hines, Robert E Martell, Richard A Larson
    Abstract:

    PURPOSE: We sought to determine whether therapy with single-agent Fludarabine compared with chlorambucil alone or the combination of both agents had an impact on the incidence and spectrum of infections among a series of previously untreated patients with B-cell chronic lymphocytic leukemia (CLL). PATIENTS AND METHODS: Five hundred fifty-four previously untreated CLL patients with intermediate/high-risk Rai-stage disease were enrolled onto an intergroup protocol. Patients were randomized to therapy with chlorambucil, Fludarabine, or Fludarabine plus chlorambucil. Data pertaining to infection were available on 518 patients. Differences in infections among treatment arms were tested with the Kruskal-Wallis, Wilcoxon, and χ2 tests. RESULTS: A total of 1,107 infections (241 major infections) occurred in 518 patients over the infection follow-up period (interval from study entry until either reinstitution of initial therapy, therapy with a second agent, or death). Patients treated with Fludarabine plus chloram...

Frederick R Appelbaum - One of the best experts on this subject based on the ideXlab platform.

  • impact of age on outcomes after initial therapy with chemotherapy and different chemoimmunotherapy regimens in patients with chronic lymphocytic leukemia results of sequential cancer and leukemia group b studies
    Journal of Clinical Oncology, 2013
    Co-Authors: Jennifer A Woyach, Kanti R Rai, Frederick R Appelbaum, Jonathan E Kolitz, Amy S Ruppert, Thomas S Lin, Susan M Geyer, Martin S Tallman, Andrew Belch, Vicki A Morrison
    Abstract:

    Purpose Chronic lymphocytic leukemia (CLL) is a disease of the elderly, yet few clinical trials include a significant number of older patients, and outcomes after specific therapies can be different depending on age. Patients and Methods We examined patients enrolled onto successive first-line CALGB CLL trials to determine whether efficacy of regimens varied by age, focusing on ideal chemotherapy choice and benefit of immunotherapy addition to chemotherapy in older patients. Regimens included chlorambucil, Fludarabine, Fludarabine plus rituximab (FR), Fludarabine with consolidation alemtuzumab, and FR with consolidation alemtuzumab. Results A total of 663 patients were evaluated for response, progression-free survival (PFS), and overall survival (OS) by age group. Interaction effects of Fludarabine versus chlorambucil by age group (PFS, P = .046; OS, P = .006) showed that among patients younger than 70 years, PFS and OS was improved with Fludarabine over chlorambucil (PFS: hazard ratio [HR] = 0.6, 95% CI,...

  • phase iii trial of Fludarabine plus cyclophosphamide compared with Fludarabine for patients with previously untreated chronic lymphocytic leukemia us intergroup trial e2997
    Journal of Clinical Oncology, 2007
    Co-Authors: Ian W Flinn, Frederick R Appelbaum, Richard A Larson, Donna Neuberg, Michael R Grever, Gordon W Dewald, John M Bennett, Elisabeth Paietta, Mohamad A Hussein, Dennis F Moore
    Abstract:

    Purpose The combination of Fludarabine and cyclophosphamide is an effective regimen for patients with chronic lymphocytic leukemia (CLL). However, it may be accompanied by increased toxicity compared with Fludarabine alone. E2997 is a phase III randomized Intergroup trial comparing Fludarabine and cyclophosphamide (FC arm) versus Fludarabine (F arm) alone in patients receiving their first chemotherapy regimen for CLL. Patients and Methods Symptomatic, previously untreated patients with CLL were randomly assigned to receive either Fludarabine 25 mg/m2 intravenously (IV) days 1 through 5 or cyclophosphamide 600 mg/m2 IV day 1 and Fludarabine 20 mg/m2 IV days 1 through 5. These cycles were repeated every 28 days for a maximum of six cycles. Results A total of 278 patients were randomly assigned in this Intergroup study. Treatment with Fludarabine and cyclophosphamide was associated with a significantly higher complete response (CR) rate (23.4% v 4.6%; P < .001) and a higher overall response (OR) rate (74.3% ...

  • addition of rituximab to Fludarabine may prolong progression free survival and overall survival in patients with previously untreated chronic lymphocytic leukemia an updated retrospective comparative analysis of calgb 9712 and calgb 9011
    Blood, 2005
    Co-Authors: John C Byrd, Bercedis L Peterson, Frederick R Appelbaum, Jonathan E Kolitz, Lois E Shepherd, John D Hines, Vicki A Morrison, Charles A Schiffer, Richard A Larson
    Abstract:

    Fludarabine and rituximab combination therapies in chronic lymphocytic leukemia (CLL) have yielded promising early results, but no comparative efficacy data relative to standard Fludarabine treatment regimens have been reported. To assess the effect of the addition of rituximab to Fludarabine therapy, we retrospectively compared the treatment outcome of patients with similar clinical characteristics enrolled on 2 multicenter clinical trials performed by the Cancer and Leukemia Group B and the US Intergroup that used Fludarabine and rituximab (CALGB 9712, n = 104) or Fludarabine (CALGB 9011, n = 178). In multivariate analyses controlling for pretreatment characteristics, the patients receiving Fludarabine and rituximab had a significantly better progression-free survival (PFS; P < .0001) and overall survival (OS; P = .0006) than patients receiving Fludarabine therapy. Two-year PFS probabilities were 0.67 versus 0.45, and 2-year OS probabilities were 0.93 versus 0.81. Infectious toxicity was similar between the 2 treatment approaches. These comparative data are retrospective and could be confounded by differences in supportive care or dissimilar enrollment of genetic subsets on each trial. Confirmation of these findings will require a prospective randomized trial comparing Fludarabine and rituximab to Fludarabine.

  • therapy related myeloid leukemias are observed in patients with chronic lymphocytic leukemia after treatment with Fludarabine and chlorambucil results of an intergroup study cancer and leukemia group b 9011
    Journal of Clinical Oncology, 2002
    Co-Authors: Vicki A Morrison, Kanti R Rai, Bercedis L Peterson, Frederick R Appelbaum, Jonathan E Kolitz, Laurence Elias, John D Hines, Richard A Larson, Lois Shepherd, Charles A Schiffer
    Abstract:

    PURPOSE: Patients with chronic lymphocytic leukemia (CLL) may have disease transformation to non-Hodgkin’s lymphoma or prolymphocytic leukemia; however, development of therapy-related acute myeloid leukemia (t-AML) is unusual. A series of patients enrolled onto an intergroup CLL trial were examined for this complication. PATIENTS AND METHODS: A total of 544 previously untreated B-cell CLL patients were enrolled onto a randomized intergroup study comparing treatment with chlorambucil, Fludarabine, or Fludarabine plus chlorambucil. Case report forms from 521 patients were reviewed for t-AML. RESULTS: With a median follow-up of 4.2 years, six patients (1.2%) to date have developed therapy-related myelodysplastic syndrome (t-MDS; n = 3), t-AML (n = 2), or t-MDS evolving to t-AML (n = 1), from 27 to 53 months (median, 34 months) after study entry. This included five (3.5%) of 142 patients treated with Fludarabine plus chlorambucil and one (0.5%) of 188 receiving Fludarabine; no chlorambucil-treated patients de...

  • impact of therapy with chlorambucil Fludarabine or Fludarabine plus chlorambucil on infections in patients with chronic lymphocytic leukemia intergroup study cancer and leukemia group b 9011
    Journal of Clinical Oncology, 2001
    Co-Authors: Vicki A Morrison, Kanti R Rai, Bercedis L Peterson, Frederick R Appelbaum, Jonathan E Kolitz, Laurence Elias, Lois E Shepherd, John D Hines, Robert E Martell, Richard A Larson
    Abstract:

    PURPOSE: We sought to determine whether therapy with single-agent Fludarabine compared with chlorambucil alone or the combination of both agents had an impact on the incidence and spectrum of infections among a series of previously untreated patients with B-cell chronic lymphocytic leukemia (CLL). PATIENTS AND METHODS: Five hundred fifty-four previously untreated CLL patients with intermediate/high-risk Rai-stage disease were enrolled onto an intergroup protocol. Patients were randomized to therapy with chlorambucil, Fludarabine, or Fludarabine plus chlorambucil. Data pertaining to infection were available on 518 patients. Differences in infections among treatment arms were tested with the Kruskal-Wallis, Wilcoxon, and χ2 tests. RESULTS: A total of 1,107 infections (241 major infections) occurred in 518 patients over the infection follow-up period (interval from study entry until either reinstitution of initial therapy, therapy with a second agent, or death). Patients treated with Fludarabine plus chloram...

Veronique Turcotte - One of the best experts on this subject based on the ideXlab platform.

  • ugt2b17 modifies drug response in chronic lymphocytic leukaemia
    British Journal of Cancer, 2020
    Co-Authors: Eric P Allai, Lyne Villeneuve, Joanie Vaillancou, Michele Rouleau, Katrina Vanura, Adrie Labrie, Sophie Tremblay, Vince A, Veronique Turcotte
    Abstract:

    BACKGROUND High UGT2B17 is associated with poor prognosis in untreated chronic lymphocytic leukaemia (CLL) patients and its expression is induced in non-responders to Fludarabine-containing regimens. We examined whether UGT2B17, the predominant lymphoid glucuronosyltransferase, affects leukaemic drug response and is involved in the metabolic inactivation of anti-leukaemic agents. METHODS Functional enzymatic assays and patients' plasma samples were analysed by mass-spectrometry to evaluate drug inactivation by UGT2B17. Cytotoxicity assays and RNA sequencing were used to assess drug response and transcriptome changes associated with high UGT2B17 levels. RESULTS High UGT2B17 in B-cell models led to reduced sensitivity to Fludarabine, ibrutinib and idelalisib. UGT2B17 expression in leukaemic cells involved a non-canonical promoter and was induced by short-term treatment with these anti-leukaemics. Glucuronides of both Fludarabine and ibrutinib were detected in CLL patients on respective treatment, however UGT2B17 conjugated Fludarabine but not ibrutinib. AMP-activated protein kinase emerges as a pathway associated with high UGT2B17 in Fludarabine-treated patients and drug-treated cell models. The expression changes linked to UGT2B17 exposed nuclear factor kappa B as a key regulatory hub. CONCLUSIONS Data imply that UGT2B17 represents a mechanism altering drug response in CLL through direct inactivation but would also involve additional mechanisms for drugs not inactivated by UGT2B17.

  • ugt2b17 modifies drug response in chronic lymphocytic leukaemia
    British Journal of Cancer, 2020
    Co-Authors: Eric P Allain, Lyne Villeneuve, Michele Rouleau, Katrina Vanura, Sophie Tremblay, Joanie Vaillancourt, Vincent Bat, Patrick Caron, Adrien Labriet, Veronique Turcotte
    Abstract:

    High UGT2B17 is associated with poor prognosis in untreated chronic lymphocytic leukaemia (CLL) patients and its expression is induced in non-responders to Fludarabine-containing regimens. We examined whether UGT2B17, the predominant lymphoid glucuronosyltransferase, affects leukaemic drug response and is involved in the metabolic inactivation of anti-leukaemic agents. Functional enzymatic assays and patients’ plasma samples were analysed by mass-spectrometry to evaluate drug inactivation by UGT2B17. Cytotoxicity assays and RNA sequencing were used to assess drug response and transcriptome changes associated with high UGT2B17 levels. High UGT2B17 in B-cell models led to reduced sensitivity to Fludarabine, ibrutinib and idelalisib. UGT2B17 expression in leukaemic cells involved a non-canonical promoter and was induced by short-term treatment with these anti-leukaemics. Glucuronides of both Fludarabine and ibrutinib were detected in CLL patients on respective treatment, however UGT2B17 conjugated Fludarabine but not ibrutinib. AMP-activated protein kinase emerges as a pathway associated with high UGT2B17 in Fludarabine-treated patients and drug-treated cell models. The expression changes linked to UGT2B17 exposed nuclear factor kappa B as a key regulatory hub. Data imply that UGT2B17 represents a mechanism altering drug response in CLL through direct inactivation but would also involve additional mechanisms for drugs not inactivated by UGT2B17.

Lv Che - One of the best experts on this subject based on the ideXlab platform.

  • an ultrasonic nanobubble mediated pnp Fludarabine suicide gene system a new approach for the treatment of hepatocellular carcinoma
    PLOS ONE, 2018
    Co-Authors: O Zhang, Youming Zhang, Lihua Zhang, Mingna Che, Wei Che, Lv Che
    Abstract:

    Objective The purpose of this study is to generate an ultrasonic nanobubble (NB)-mediated purine nucleoside phosphorylase (PNP)/Fludarabine suicide gene system for the treatment of human hepatocellular carcinoma (HCC). Methods NBs were prepared from a mixture the phospholipids 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dipalmitoyl-sn-glycero-3-phosphate (DPPA), perfluoropropane gas and other materials using the high shear dispersion method. NBs treated with ultrasound irradiation functioned as a gene-transfer system, and a self-constructed suicide gene expression plasmid, pcDNA3.1(+)/PNP, treated with Fludarabine functioned as a therapeutic gene. This system was used to determine the cytotoxic effects of PNP/Fludarabine on HepG2 cells and SMMC7721 cells. Results 1. NBs with a small diameter (208–416 nm) and at a high concentration and fine homogeneity were prepared under the optimal method. 2. The pcDNA3.1(+)/PNP plasmid was efficiently transfected into HCC cells using ultrasonic NBs. 3. At 0.75μg/ml Fludarabine, PNP/Fludarabine showed marked cytotoxic effects toward HepG2 and SMMC7721 cells. PNP/Fludarabine achieved the same effect against both SMMC7721 and HepG2 cells but at a lower concentration of Fludarabine for the latter. 4. Bystander effects: a 10–20% decrease in the cell survival rate was observed when only 5–10% of transfected cells were PNP positive. Conclusions NBs constitute a non-toxic, stable and effective gene-delivery platform. The PNP/Fludarabine suicide gene system inhibited the growth of HCC cells, induced HCC cell apoptosis, and caused a notable bystander effect at a low Fludarabine concentration. This study establishes an important new method for miniaturizing microbubbles and improving a new NB-mediated approach for gene therapy of HCC.

Susan Obrien - One of the best experts on this subject based on the ideXlab platform.

  • 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
    Journal of Clinical Oncology, 2012
    Co-Authors: Gautam Borthakur, Susan Obrien, William Plunkett, Varsha Gandhi, Farhad Ravandi, Jorge E. Cortes, Stefan Faderl, Tapan M Kadia, Zeev Estrov, Joyce Bass
    Abstract:

    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 da...

  • cyclophosphamide Fludarabine alemtuzumab and rituximab as salvage therapy for heavily pretreated patients with chronic lymphocytic leukemia
    Blood, 2011
    Co-Authors: Xavier Badoux, Susan Obrien, Alessandra Ferrajoli, Stefan Faderl, Susan Lerner, Michael J Keating, Xuemei Wang, Jan A Burger, Charles A Koller, Hagop M Kantarjian
    Abstract:

    Patients with relapsed chronic lymphocytic leukemia (CLL) and high-risk features, such as Fludarabine refractoriness, complex karyotype, or abnormalities of chromosome 17p, experience poor outcomes after standard fludaradine-based regimens. Alemtuzumab is a chimeric CD52 monoclonal antibody with activity in CLL patients with Fludarabine-refractory disease and 17p deletion. We report the outcome for 80 relapsed or refractory patients with CLL enrolled in a phase 2 study of cyclophosphamide, Fludarabine, alemtuzumab, and rituximab (CFAR). All patients were assessed for response and progression according to the 1996 CLL-working group criteria. For the intention-to-treat analysis, the overall response rate was 65%, including 29% complete response. The estimated progression-free survival was 10.6 months and median overall survival was 16.7 months. Although we noted higher complete response in high-risk patients after CFAR compared with a similar population who had received Fludarabine, cyclophosphamide, and rituximab as salvage therapy, there was no significant improvement in progression-free survival and overall survival appeared worse. CFAR was associated with a high rate of infectious complications with 37 patients (46%) experiencing a serious infection during therapy and 28% of evaluable patients experiencing late serious infections. Although CFAR produced good response rates in this highly pretreated high-risk group of patients, there was no benefit in survival outcomes.

  • phase i ii study of oxaliplatin Fludarabine cytarabine and rituximab combination therapy in patients with richter s syndrome or Fludarabine refractory chronic lymphocytic leukemia
    Journal of Clinical Oncology, 2008
    Co-Authors: Apostolia Maria Tsimberidou, Farhad Ravandikashani, Susan Obrien, Guillermo Garciamanero, Alessandra Ferrajoli, William Plunkett, William G Wierda, Razelle Kurzrock, Thomas J Kipps
    Abstract:

    Purpose Richter's syndrome (RS) and Fludarabine-refractory chronic lymphocytic leukemia (CLL) are associated with poor clinical outcomes. We conducted a phase I-II trial of oxaliplatin, Fludarabine, cytarabine, and rituximab (OFAR) in these diseases. Patients and Methods The OFAR regimen consisted of increasing doses of oxaliplatin (17.5, 20, or 25 mg/m2/d) on days 1 to 4 (phase I), Fludarabine 30 mg/m2 on days 2 to 3, cytarabine 1 g/m2 on days 2 to 3, rituximab 375 mg/m2 on day 3 of cycle 1 and day 1 of subsequent cycles, and pegfilgrastim 6 mg on day 6, every 4 weeks for a maximum of six courses. Dose-limiting toxicity (DLT) was defined as any nonhematologic, treatment-related toxicity ≥ grade 3. Results Fifty patients were treated (20 patients had RS, and 30 had CLL). The highest tolerated oxaliplatin dose was 25 mg/m2, which was the highest dose tested. DLT was not observed. Pharmacodynamic analyses demonstrated enhanced leukemia cell killing by oxaliplatin in the presence of Fludarabine and cytarabin...

  • results of the Fludarabine and cyclophosphamide combination regimen in chronic lymphocytic leukemia
    Journal of Clinical Oncology, 2001
    Co-Authors: Susan Obrien, Francis J. Giles, Jorge E. Cortes, Susan Lerner, Hagop M Kantarjian, Miloslav Beran, Charles Koller, Michael J Keating
    Abstract:

    PURPOSE: To assess the efficacy of combination therapy with Fludarabine and cyclophosphamide in patients with chronic lymphocytic leukemia (CLL) based on data suggesting in vitro synergistic activity of the two agents. PATIENTS AND METHODS: A total of 128 patients with CLL were treated with Fludarabine 30 mg/m2 intravenously daily for 3 days and cyclophosphamide at either 500 mg/m2 daily for 3 days (n = 11), 350 mg/m2/d for 3 days (n = 26), or 300 mg/m2 daily for 3 days (n = 91). The cyclophosphamide dose was decreased because of myelosuppression in the early part of the study. Patients were divided into four groups based on the expectation for response to single-agent Fludarabine, including previously untreated patients, patients previously treated with alkylating agents, patients successfully treated with alkylating agents and Fludarabine but relapsing, and patients refractory to Fludarabine with or without alkylating agents. RESULTS: Fludarabine and cyclophosphamide produced ≥ 80% response rates in all...

  • infections in patients with chronic lymphocytic leukemia treated with Fludarabine
    Annals of Internal Medicine, 1998
    Co-Authors: Elias Anaissie, Susan Obrien, Susan Lerner, Hagop M Kantarjian, Dimitrios P Kontoyiannis, L E Robertson, Michael J Keating
    Abstract:

    Background: Fludarabine, a purine analogue with activity in chronic lymphocytic leukemia, is usually well tolerated. Although serious infections after Fludarabine therapy have been described, a sys...