Online citations, reference lists, and bibliographies.
← Back to Search

Mitoxantrone, Etoposide, And Cytarabine With Or Without Valspodar In Patients With Relapsed Or Refractory Acute Myeloid Leukemia And High-risk Myelodysplastic Syndrome: A Phase III Trial (E2995).

P. Greenberg, Sandra J. Lee, R. Advani, M. Tallman, B. Sikic, L. Letendre, K. Dugan, B. Lum, D. L. Chin, G. Dewald, E. Paietta, J. Bennett, J. Rowe
Published 2004 · Medicine

Save to my Library
Download PDF
Analyze on Scholarcy Visualize in Litmaps
Reduce the time it takes to create your bibliography by a factor of 10 by using the world’s favourite reference manager
Time to take this seriously.
Get Citationsy
PURPOSE To determine whether adding the multidrug resistance gene-1 (MDR-1) modulator valspodar (PSC 833; Novartis Pharmaceuticals, Hanover, NJ) to chemotherapy provided clinical benefit to patients with poor-risk acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS). PATIENTS AND METHODS A phase III randomized study was performed using valspodar plus mitoxantrone, etoposide, and cytarabine (PSC-MEC; n=66) versus MEC (n=63) to treat patients with relapsed or refractory AML and high-risk MDS. RESULTS For the PSC-MEC versus MEC arms, complete response (CR) was achieved in 17% versus 25% of patients, respectively (P=not significant). For patients who had not received prior intensive chemotherapy (ie, with secondary AML or high-risk MDS), the CR rate was increased--35% versus 15% for the remaining patients (P=.018); CR rates did not differ between treatment arms. The median disease-free survival in those achieving CR was similar in the two arms (10 versus 9.3 months) as was the patients' overall survival (4.6 versus 5.4 months). The CR rates in MDR+ (69% of patients) versus MDR- patients were similar for those receiving either chemotherapy regimen (16% versus 24%). The CR rate for unfavorable cytogenetic patients (45% of patients) was 13% compared to the remainder, 28% (P=.09). Population pharmacokinetic analysis demonstrated that the clearances of mitoxantrone and etoposide were decreased by 59% and 50%, respectively, supporting the empiric dose reductions in the PSC-MEC arm designed in anticipation of drug interactions between valspodar and the chemotherapeutic agents. CONCLUSION CR rates and overall survival were not improved by using PSC-MEC compared to MEC chemotherapy alone in patients with poor-risk AML or high-risk MDS.
This paper references
Nonparametric Estimation from Incomplete Observations
E. Kaplan (1958)
An international system for human cytogenetic nomenclature
Iscn (1978)
Nonparametrics: Statistical Methods Based on Ranks
Mitchell J. Mergenthaler (1979)
Methodology of population pharmacokinetics, in, Garrett ER, Hirtz J (eds), Drug Fate and Metabolism
SL Beal (1985)
Population pharmacokinetics.
T. Ludden (1988)
Daunorubicin in patients with relapsed and refractory acute nonlymphoblastic leukemia previously treated with anthracycline
T. Velu (1988)
Overexpression of the MDRL gene in blast cells from patients with acute myelocytic leukemia is associated with decreased anthracycline accumulation that can be restored by cyclosporin‐A
K. Nooter (1990)
Novel assay method for mitoxantrone in plasma, and its application in cancer patients.
O. Y. Hu (1990)
Expression of mdr1 and mdr3 multidrug-resistance genes in human acute and chronic leukemias and association with stimulation of drug accumulation by cyclosporine.
H. Herweijer (1990)
MDR1 transcript levels as an indication of resistant disease in acute myelogenous leukaemia
H. Sato (1990)
Overexpression of the mdr1 gene in blast cells from patients with acute myelocytic leukemia is associated with stimulation of drug accumulation that can be restored by cyclosporin-A
K Nooter (1990)
In vivo circumvention of P-glycoprotein-mediated multidrug resistance of tumor cells with SDZ PSC 833.
D. Bösch (1991)
Resistance modification by PSC-833, a novel non-immunosuppressive cyclosporin [corrected].
Twentyman Pr (1991)
Multidrug resistance (mdr1) gene expression in adult acute leukemias: correlations with treatment outcome and in vitro drug sensitivity.
J. Marie (1991)
Resistance modification by PSC-833, a novel non-immunosuppressive cyclosporin A
P. Twentyman (1991)
Categorical Data Analysis.
D. Lendrem (1991)
Expression of the multidrug resistance gene product (P‐glycoprotein) in myelodysplasia is associated with a stem cell phenotype
A. List (1991)
Feasibility of using quinine, a potential multidrug resistance-reversing agent, in combination with mitoxantrone and cytarabine for the treatment of acute leukemia.
E. Solary (1992)
Alteration of etoposide pharmacokinetics and pharmacodynamics by cyclosporine in a phase I trial to modulate multidrug resistance.
B. Lum (1992)
SDZ PSC 833, A non‐immunosuppressive cyclosporine: Its potency in overcoming P‐glycoprotein‐mediated multidrug resistance of murine leukemia
R. P. Keller (1992)
Pharmacologic interactions between the resistance‐modifying cyclosporine sdz psc 833 and etoposide (VP 16–213) enhance In Vivo cytostatic activity and toxicity
R. P. Keller (1992)
Clinical significance of multidrug resistance P-glycoprotein expression on acute nonlymphoblastic leukemia cells at diagnosis.
L. Campos (1992)
Predominance of functional multidrug resistance (MDR-1) phenotype in CD34+ acute myeloid leukemia cells.
P. A. T. Boekhorst (1993)
Phase I/II trial of cyclosporine as a chemotherapy-resistance modifier in acute leukemia.
A. List (1993)
Multidrug resistance: clinical relevance in acute leukemia.
A. List (1993)
Predominance of functional multidrug resistance (MDR-1) phenotype in CD34+ acute myeloid leukemia cells.
P. T. Te Boekhorst (1993)
A Sensitive and Simple High‐Performance Liquid Chromatographic Method for the Determination of Mitoxantrone in Plasma
L. Slørdal (1993)
Clinical significance of P-glycoprotein in multidrug resistance malignancies.
R. Arceci (1993)
A Southwest Oncology Group study
T. Jenkins (1993)
Clinical significance of P-glycoprotein in multidrug resistance malignancies [editorial] [see comments]
R. Arceci (1993)
A Sensitive and Simple High‐Performance Liquid Chromatographic Method for the Determination of Doxorubicin and Its Metabolites in Plasma
A. Andersen (1993)
P‐glycoprotein expression on acute myeloid leukaemia blast cells at diagnosis predicts response to chemotherapy and survival
P. Wood (1994)
Expression of the multidrug resistance P-glycoprotein and its relationship to hematological characteristics and response to treatment in myelodysplastic syndromes.
P. Lepelley (1994)
Group sequential designs for one-sided and two-sided hypothesis testing with provision for early stopping in favor of the null hypothesis
S. Pampallona (1994)
Escalating dose of mitoxantrone with high-dose cyclophosphamide, carmustine, and etoposide in patients with refractory lymphoma undergoing autologous bone marrow transplantation.
M. Attal (1994)
Modulation of multidrug resistance in de novo adult acute myeloid leukemia: variable efficacy of reverting agents in vitro. Eastern Cooperative Oncology Group.
E. Paietta (1995)
Increased expression of the multidrug resistance-associated protein gene in relapsed acute leukemia.
E. Schneider (1995)
A stratification system for evaluating and selecting therapies in patients with relapsed or primary refractory acute myelogenous leukemia.
E. Estey (1996)
Methods to detect P-glycoprotein-associated multidrug resistance in patients' tumors: consensus recommendations.
W. T. Beck (1996)
Pharmacological considerations in the modulation of multidrug resistance.
G. Fisher (1996)
Phase I study of etoposide with SDZ PSC 833 as a modulator of multidrug resistance in patients with cancer.
D. Boote (1996)
Acute myeloid leukemia in the elderly: assessment of multidrug resistance (MDR1) and cytogenetics distinguishes biologic subgroups with remarkably distinct responses to standard chemotherapy. A Southwest Oncology Group study.
C. Leith (1997)
Non-P-glycoprotein drug export mechanisms of multidrug resistance.
A. List (1997)
International scoring system for evaluating prognosis in myelodysplastic syndromes.
P. Greenberg (1997)
Acute Myeloid Leukemia in the Elderly : Assessment of Multidrug Resistance ( MDR 1 ) and Cytogenetics Distinguishes Biologic Subgroups With Remarkably Distinct Responses to Standard Chemotherapy
C. Leith (1997)
Classical multidrug resistance in acute myeloid leukaemia
E. Paietta (1997)
Pharmacologic approaches to reversing multidrug resistance.
B. Sikic (1997)
Quinine improves the results of intensive chemotherapy in myelodysplastic syndromes expressing P glycoprotein: results of a randomized study
Wattel (1998)
Assay for etoposide in human serum using solid-phase extraction and high-performance liquid chromatography with fluorescence detection.
K. Manouilov (1998)
Acute myeloid leukemia.
B. Löwenberg (1999)
Frequency and Clinical Significance of the Expression of the Multidrug Resistance Proteins MDR 1 / P-Glycoprotein , MRP 1 , and LRP in Acute Myeloid Leukemia . A Southwest Oncology Group Study
C. Leith (1999)
Mitoxantrone, etoposide, and cytarabine plus cyclosporine for patients with relapsed or refractory acute myeloid leukemia
M. Tallman (1999)
Frequency and clinical significance of the expression of the multidrug resistance proteins MDR1/P-glycoprotein, MRP1, and LRP in acute myeloid leukemia: a Southwest Oncology Group Study.
C. Leith (1999)
Treatment of refractory/relapsed AML with chemotherapy plus the multi-drug resistance modulator PSC833 (Valspodar)
R Advani (1999)
Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group Study.
M. Slovak (2000)
Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group study
M. Slovak (2000)
Phase I/II study of the P-glycoprotein modulator PSC 833 in patients with acute myeloid leukemia.
R. Dorr (2001)
Population Pharmacokinetics of Etoposide: Application to Therapeutic Drug Monitoring
J. Ciccolini (2002)
Phase 3 study of the multidrug resistance modulator PSC-833 in previously untreated patients 60 years of age and older with acute myeloid leukemia: Cancer and Leukemia Group B Study 9720.
M. Baer (2002)
A phase I/II study of the MDR modulator Valspodar (PSC 833) combined with daunorubicin and cytarabine in patients with relapsed and primary refractory acute myeloid leukemia.
A. Gruber (2003)

This paper is referenced by
Consolidation in AML: Abundant opinion and much unknown.
Nir Weigert (2021)
Investigation of MRP 1 and ABCG 2 Gene Expression in Chronic Myeloid Leukemia ( CML ) Patients 1
Saeed Solali (2021)
Improved outcome of children with relapsed/refractory acute myeloid leukemia by addition of cladribine to re‐induction chemotherapy
M. Ruan (2021)
Dual Targeting of EGFR with PLK1 Exerts Therapeutic Synergism in Taxane-Resistant Lung Adenocarcinoma by Suppressing ABC Transporters
Sol-Bi Shin (2021)
Cancer therapies based on targeted protein degradation — lessons learned with lenalidomide
M. Jan (2021)
Flavia Cunha Vasconcelos (2021)
Targeting CXCR4 in AML and ALL
Daniel Cancilla (2020)
Intercellular Mitochondrial Transfer in the Tumor Microenvironment
Hana Sahinbegovic (2020)
At the Bedside: Profiling and treating patients with CXCR4‐expressing cancers
Miguel Martín (2020)
Leukemia Stem Cell Release From the Stem Cell Niche to Treat Acute Myeloid Leukemia
A. Villatoro (2020)
CXCR4 Antagonists as Stem Cell Mobilizers and Therapy Sensitizers for Acute Myeloid Leukemia and Glioblastoma?
Vashendriya V. V. Hira (2020)
The Pyrazolo[3,4-d]pyrimidine Derivative, SCO-201, Reverses Multidrug Resistance Mediated by ABCG2/BCRP
Sophie E B Ambjørner (2020)
MEC (mitoxantrone, etoposide, and cytarabine) induces complete remission and is an effective bridge to transplant in acute myeloid leukemia
Giovanni Marconi (2020)
Efficacy of mitoxantrone-based salvage therapies in relapsed or refractory acute myeloid leukemia in the Mayo Clinic Cancer Center: Analysis of survival after 'CLAG-M' vs. 'MEC'.
C. Scheckel (2020)
Clinical Perspective of FDA Approved Drugs With P-Glycoprotein Inhibition Activities for Potential Cancer Therapeutics
Jiun-I Lai (2020)
The Evolving AML Genomic Landscape: Therapeutic Implications.
S. Horibata (2020)
Nonionic surfactants modulate the transport activity of ATP-binding cassette (ABC) transporters and solute carriers (SLC): Relevance to oral drug absorption.
A. Al-Ali (2019)
Management of primary refractory acute myeloid leukemia in the era of targeted therapies
C. McMahon (2019)
Increased mitochondrial apoptotic priming with targeted therapy predicts clinical response to re‐induction chemotherapy
J. S. Garcia (2019)
A phase 1 study of the antibody‐drug conjugate brentuximab vedotin with re‐induction chemotherapy in patients with CD30‐expressing relapsed/refractory acute myeloid leukemia
Rupa Narayan (2019)
ABC Transporter-Mediated Multidrug-Resistant Cancer.
H. Amawi (2019)
Quizartinib versus salvage chemotherapy in relapsed or refractory FLT3-ITD acute myeloid leukaemia (QuANTUM-R): a multicentre, randomised, controlled, open-label, phase 3 trial.
J. Cortes (2019)
Integrating resistance functions to predict response to induction chemotherapy in de novo acute myeloid leukemia
Yu-Chiao Chiu (2019)
Clinical Significance of ABCB1 in Acute Myeloid Leukemia: A Comprehensive Study
T. Boyer (2019)
Significance of ABC Transporters in the Treatment of Intrinsically Resistant Acute Myeloid Leukemia
S. Horibata (2019)
Development of liposomal pemetrexed for enhanced therapy against multidrug resistance mediated by ABCC5 in breast cancer
F. Bai (2018)
Knockdown of the Wnt receptor Frizzled-1 (FZD1) reduces MDR1/P-glycoprotein expression in multidrug resistant leukemic cells and inhibits leukemic cell proliferation.
Y. Wang (2018)
MDR1 in immunity: friend or foe?
Marion Bossennec (2018)
A phase I study of lenalidomide plus chemotherapy with mitoxantrone, etoposide, and cytarabine for the reinduction of patients with acute myeloid leukemia
D. DeAngelo (2018)
A Bayesian Network Meta-Analysis Comparing the Efficacies of Eleven Novel Therapies with the Common Salvage Regimen for Relapsed or Refractory Acute Myeloid Leukemia
J. Huang (2018)
Treatment of relapsed/refractory acute myeloid leukaemia in adults
A. Rashidi (2018)
Breast Cancer, Version 4.2017, NCCN Clinical Practice Guidelines in Oncology.
W. Gradishar (2018)
See more
Semantic Scholar Logo Some data provided by SemanticScholar