Evidence map›Paper›PMID 24619498›Full record

ArticleCancer chemotherapy and pharmacology2014

Clinical pharmacology of an atrasentan and docetaxel regimen in men with hormone-refractory prostate cancer.

Islam R Younis, Daniel J George, Terence J McManus, Herbert Hurwitz, Patricia Creel, Andrew J Armstrong, Jing Jie Yu, Kristina Bacon, Gerald Hobbs, Cody J Peer and 1 more

Open access · greenAbstract read
In one paragraph

Article in Cancer chemotherapy and pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
1.2field-weighted citation impact, top 20% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 1 synthesis or guideline pooled it, 7 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 5 institutions in 1 country.

Islam R YounisMary Babb Randolph (MBR) Cancer Center, West Virginia University, PO Box 9300, Morgantown, WV, 26506, USA.
Daniel J George
Terence J McManus
Herbert Hurwitz
Patricia Creel
Andrew J Armstrong
Jing Jie Yu
Kristina Bacon
Gerald Hobbs
Cody J Peer
William P Petros
West Virginia University · USDuke University · USWest Virginia University Hospitals · USDuke Medical Center · USUnited States Food and Drug Administration · US

Funding

Women's Cancer Research ProgramP30CA014236 · NCI · DUKE UNIVERSITY · PI JOHN N. NORTON · 1985 to 2026
$174.8M
WV INBRE: The Inhibitor of Growth Family Member 4 (ING4) inhibits L-Type Amino Acid Transporter 1 (LAT1) expression to suppress Breast CancerP20GM103434 · NIGMS · MARSHALL UNIVERSITY · PI Travis Salisbury · 2012 to 2026
$61.1M
WVU &MU NEW FACULTY GRANTSP20RR016477 · NCRR · MARSHALL UNIVERSITY · PI RANKIN, GARY O · 2001 to 2011
$35.5M
West Virginia Flow Cytometry Core FacilityP30GM103488 · NIGMS · WEST VIRGINIA UNIVERSITY · PI CUFF, CHRISTOPHER F · 2012 to 2016
$4.8M
COBRE FOR SIGNAL TRANSDUCTION AND CANCER PHASE IIIP30RR032138 · NCRR · WEST VIRGINIA UNIVERSITY · PI GIBSON, LAURA F. · 2011 to 2011
$1.1M
NCI NIH HHS P30 CA014236NCRR NIH HHS 5P20RR016477NCRR NIH HHS P20 RR016477NCRR NIH HHS P30 RR032138NIGMS NIH HHS P20 GM103434NIGMS NIH HHS P30 GM103488
6 · The paper itself

Abstract

purposeThis study was conducted to evaluate potential pharmacokinetic interactions between docetaxel and atrasentan as part of a phase I/II clinical trial.

methodsPatients with prostate cancer were treated with intravenous docetaxel (60-75 mg/m(2)) every 3 weeks and oral atrasentan (10 mg) daily starting on day 3 of cycle 1 and then given continuously. The pharmacokinetics of both drugs were evaluated individually (cycle 1, day 1 for docetaxel; day 21 for atrasentan) and in combination (cycle 2, day 1 for both drugs). Pharmacogenomics of alpha-1-acid glycoprotein (AAG) were also explored.

resultsPaired pharmacokinetic data sets for both drugs were evaluable in 21 patients. Atrasentan was rapidly absorbed and plasma concentrations varied over a fourfold range at steady state within a typical patient. The median apparent oral clearance of atrasentan was 17.4 L/h in cycle 1 and was not affected by docetaxel administration (p = 0.9). Median systemic clearance of docetaxel was 51.1 L/h on the first cycle and significantly slower (p = 0.01) compared with that obtained during co-administration of atrasentan, 61.6 L/h. Docetaxel systemic clearance in cycle 1 was 70.0 L/h in patients homozygous for a variant allele in AAG compared with 44.5 L/h in those with at least one wild-type allele (p = 0.03).

conclusionGenetic polymorphism in AAG may explain some inter-patient variability in docetaxel pharmacokinetics. The systemic clearance of docetaxel is increased by approximately 21 % when given concomitantly with atrasentan; however, atrasentan pharmacokinetics does not appear to be influenced by docetaxel administration.

Indexed as

AgedAged, 80 and overAntineoplastic AgentsAtrasentanDocetaxelHumansMaleMiddle AgedProstatic NeoplasmsPyrrolidinesTaxoidsAntineoplastic AgentsAtrasentanDocetaxelPyrrolidinesTaxoids

Identifiers

PMID24619498
PMCPMC4010098
OpenAlexW2013973010

What OpenQuestion holds

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Registered trials

None linked

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.