Evidence map›Paper›PMID 20716770›Full record

Trial reportBlood2010

Zosuquidar, a novel modulator of P-glycoprotein, does not improve the outcome of older patients with newly diagnosed acute myeloid leukemia: a randomized, placebo-controlled trial of the Eastern Cooperative Oncology Group 3999.

Larry D Cripe, Hajime Uno, Elisabeth M Paietta, Mark R Litzow, Rhett P Ketterling, John M Bennett, Jacob M Rowe, Hillard M Lazarus, Selina Luger, Martin S Tallman

Registry-linked trialOpen access · greenAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Blood, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00046930 (A Randomized, Placebo-Controlled, Double Blind, Trial of the Administration of the MDR Modulator, Zosuquidar Trihydrochloride), which is not on this map. Cited by 109 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
109citing papers in PubMed, 2 pooled it
9.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00046930 phase3completednot on this map

A Randomized, Placebo-Controlled, Double Blind, Trial of the Administration of the MDR Modulator, Zosuquidar Trihydrochloride (LY335979), During Conventional Induction and Post-Remission Therapy in Patients Greater Than 60 Years of Age With Newly Diagnosed Acute Myeloid Leukemia, Refractory Anemia With Excess Blasts in Transformation or High-Risk Refractory Anemia With Excess Blasts

TypeinterventionalSponsorEastern Cooperative Oncology GroupRan2002Enrolled449ConditionsLeukemia, Myelodysplastic SyndromesArmsfilgrastim, sargramostim, cytarabine, daunorubicin hydrochloride, zosuquidar trihydrochloride
3 · Its place in the literature

Who cites it

109 citing papers in PubMed, 2 syntheses or guidelines pooled it, 232 citations in OpenAlex.

  1. Pooled it
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  15. Understanding and overcoming multidrug resistance in cancer.Nature reviews. Clinical oncology · 2025
    Review
  16. Article
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  18. Review
  19. Article
  20. Zosuquidar Promotes Antitumor Immunity by Inducing Autophagic Degradation of PD-L1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024
    Article

49 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 9 institutions in 2 countries.

Larry D CripeIndiana University Simon Cancer Center, Indianapolis, IN, USA. lcripe@iupui.edu
Hajime Uno
Elisabeth M Paietta
Mark R Litzow
Rhett P Ketterling
John M Bennett
Jacob M Rowe
Hillard M Lazarus
Selina Luger
Martin S Tallman
Montefiore Medical Center · USCase Comprehensive Cancer CenterDana-Farber Cancer Institute · USIndiana University – Purdue University Indianapolis · USMayo Clinic in Arizona · USMemorial Sloan Kettering Cancer Center · USRambam Health Care Campus · ILUniversity of Pennsylvania · USUniversity of Rochester · US

Funding

ECOG OPERATIONS OFFICE (IBCSG)U10CA021115 · NCI · UNIVERSITY OF WISCONSIN MADISON · PI COMIS, ROBERT L · 1985 to 2013
$132.6M
ECOG Statistical Office Data Management GrantU10CA066636 · NCI · FRONTIER SCI &TECHNOLOGY RSCH FDN, INC · PI GRAY, ROBERT J · 1994 to 2013
$39.5M
PROVIDE STATISTICAL SERVICESU10CA023318 · NCI · DANA-FARBER CANCER INSTITUTE · PI GRAY, ROBERT J · 1985 to 2013
$33.4M
ECOG Specimen BankingU24CA114737 · NCI · FRONTIER SCI &TECHNOLOGY RSCH FDN, INC · PI COMIS, ROBERT L · 2005 to 2014
$9.3M
ECOG Clinical TrialsU10CA017145 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI BENSON, AL B · 1985 to 2013
$6.1M
ONCOLOGYU10CA015488 · NCI · UNIVERSITY OF PENNSYLVANIA · PI LUGER, SELINA M · 1985 to 2013
$5.6M
SOUTHWEST ONCOLOGY GROUPU10CA011083 · NCI · UNIVERSITY OF ROCHESTER · PI FRIEDBERG, JONATHAN W · 1985 to 2013
$5.5M
ONCOLOGYU10CA049883 · NCI · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI MILLER, KATHY D. · 1989 to 2013
$4.0M
ONCOLOGYU10CA013650 · NCI · MAYO CLINIC ROCHESTER · PI HABERMANN, THOMAS MATTHEW · 1985 to 2013
$3.1M
ONCOLOGYU10CA014958 · NCI · YESHIVA UNIVERSITY · PI SPARANO, JOSEPH A. · 1985 to 2013
$2.2M
NCI NIH HHS CA11083NCI NIH HHS CA13650NCI NIH HHS CA14958NCI NIH HHS CA15488NCI NIH HHS CA17145NCI NIH HHS CA21115NCI NIH HHS CA23318NCI NIH HHS CA49883NCI NIH HHS CA66636NCI NIH HHS U10 CA011083NCI NIH HHS U10 CA013650NCI NIH HHS U10 CA014958NCI NIH HHS U10 CA015488NCI NIH HHS U10 CA017145NCI NIH HHS U10 CA021115NCI NIH HHS U10 CA023318NCI NIH HHS U10 CA049883NCI NIH HHS U10 CA066636NCI NIH HHS U24 CA114737
6 · The paper itself

Abstract

Zosuquidar, which modulates P-glycoprotein (P-gp) with minimal delay of anthracycline clearance, may reverse P-gp-mediated resistance in acute myeloid leukemia without increased toxicity. A total of 449 adults older than 60 years with acute myeloid leukemia or high-risk myelodysplastic syndrome enrolled in a randomized placebo-controlled double-blind trial (Eastern Cooperative Oncology Group 3999). Overall survival was compared between patients receiving conventional-dose cytarabine and daunorubicin and either zosuquidar (550 mg; 212 patients) or placebo (221 patients). Median and 2-year overall survival values were 7.2 months and 20% on zosuquidar and 9.4 months and 23% on placebo, respectively (P = .281). Remission rate was 51.9% on zosuquidar and 48.9% on placebo. All cause mortality to day 42 was not different (zosuquidar 22.2% vs placebo 16.3%; P = .158). In vitro modulation of P-gp activity by zosuquidar and expression of P-gp, multidrug resistance-related protein 1, lung resistance protein, and breast cancer resistance protein, were comparable in the 2 arms. Poor-risk cytogenetics were more common in P-gp(+) patients. P-gp expression and cytogenetics were correlated, though independent prognostic factors. We conclude that zosuquidar did not improve outcome in older acute myeloid leukemia, in part, because of the presence P-gp independent mechanisms of resistance. This trial is registered at www.clinicaltrials.gov as #NCT00046930.

Indexed as

AgedAged, 80 and overAntineoplastic AgentsATP Binding Cassette Transporter, Subfamily B, Member 1DaunorubicinDibenzocycloheptenesFemaleHumansLeukemia, Myeloid, AcuteMaleMultivariate AnalysisPlacebosPrognosisQuinolinesRemission InductionSurvival AnalysisAntineoplastic AgentsATP Binding Cassette Transporter, Subfamily B, Member 1DaunorubicindaunorubicinolDibenzocycloheptenesPlacebosQuinolineszosuquidar trihydrochloride

Identifiers

PMID20716770
PMCPMC2993615
OpenAlexW2091371557

What OpenQuestion holds

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Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.