Evidence map›Paper›PMID 29765150›Full record

ArticleBritish journal of cancer2018

Phase I studies of AZD1208, a proviral integration Moloney virus kinase inhibitor in solid and haematological cancers.

Jorge Cortes, Kenji Tamura, Daniel J DeAngelo, Johann de Bono, David Lorente, Mark Minden, Geoffrey L Uy, Hagop Kantarjian, Lisa S Chen, Varsha Gandhi and 6 more

Open access · hybridAbstract readClinical Trial, Phase IMulticenter Study
In one paragraph

Article in British journal of cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed
6.5field-weighted citation impact, top 3% 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

63 citing papers in PubMed, 112 citations in OpenAlex.

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  13. PIM kinase inhibition counters resistance to radiotherapy and chemotherapy in human prostate cancer.Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology · 2025
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3 more citing papers are in PubMed but not listed here.

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

16 authors at 7 institutions in 3 countries.

Jorge CortesDepartment of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, 1901 East Road, Houston, TX, 77054, USA.
Kenji TamuraDepartment of Breast Oncology and Medical Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo, Tokyo, 104-0045, Japan.
Daniel J DeAngeloDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Room D-2050, Boston, MA, 02215, USA.
Johann de BonoProstate Cancer Targeted Therapy Group and Drug Development Unit, Royal Marsden, Downs Road, Sutton, Surrey, SM2 5PT, UK.
David LorenteProstate Cancer Targeted Therapy Group and Drug Development Unit, Royal Marsden, Downs Road, Sutton, Surrey, SM2 5PT, UK.
Mark MindenDivision of Stem Cell and Developmental Biology, Ontario Cancer Institute, Princess Margaret Hospital, 610 University Avenue, Toronto, ON, M5G 2M9, Canada.
Geoffrey L UyDepartment of Medicine, Oncology Division, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO, 63110, USA.
Hagop KantarjianDepartment of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, 1901 East Road, Houston, TX, 77054, USA.
Lisa S ChenDepartment of Experimental Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, 1901 East Road, Houston, TX, 77054, USA.
Varsha GandhiDepartment of Experimental Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, 1901 East Road, Houston, TX, 77054, USA.
Robert GodinAstraZeneca, 35 Gatehouse Dr, Waltham, MA, 02451, USA.
Karen KeatingAstraZeneca, 35 Gatehouse Dr, Waltham, MA, 02451, USA.
Kristen McEachernAstraZeneca, 35 Gatehouse Dr, Waltham, MA, 02451, USA.
Karthick VishwanathanAstraZeneca, 35 Gatehouse Dr, Waltham, MA, 02451, USA.
Janet Elizabeth PeaseAstraZeneca, 310 Cambridge Science Park, Milton Road, Cambridge, CB4 0FZ, UK.
Emma DeanClinical Trials Unit, The Christie NHS Foundation Trust, Manchester, M20 4BX, UK. emma.dean@astrazeneca.com.
AstraZeneca (United States) · USThe University of Texas MD Anderson Cancer Center · USAstraZeneca (United Kingdom) · GBDana-Farber Cancer Institute · USOntario Institute for Cancer Research · CAThe Christie NHS Foundation Trust · GBWashington University in St. Louis · US

Funding

TYROSINE KINASE ONCOGENESIS IN MYELOID LEUKEMIAP01CA066996 · NCI · DANA-FARBER CANCER INSTITUTE · PI SCOTT A ARMSTRONG · 1996 to 2026
$52.5M
NCI NIH HHS P01 CA066996
6 · The paper itself

Abstract

backgroundProviral integration Moloney virus (PIM) kinases (PIM1, 2 and 3) are overexpressed in several tumour types and contribute to oncogenesis. AZD1208 is a potent ATP-competitive PIM kinase inhibitor investigated in patients with recurrent or refractory acute myeloid leukaemia (AML) or advanced solid tumours.

methodsTwo dose-escalation studies were performed to evaluate the safety and tolerability, and to define the maximum tolerated dose (MTD), of AZD1208 in AML and solid tumours. Secondary objectives were to evaluate the pharmacokinetics, pharmacodynamics (PD) and preliminary efficacy of AZD1208.

resultsSixty-seven patients received treatment: 32 in the AML study over a 120-900 mg dose range, and 25 in the solid tumour study over a 120-800 mg dose range. Nearly all patients (98.5%) in both studies experienced adverse events, mostly gastrointestinal (92.5%). Dose-limiting toxicities included rash, fatigue and vomiting. AZD1208 was not tolerated at 900 mg, and the protocol-defined MTD was not confirmed. AZD1208 increased CYP3A4 activity after multiple dosing, resulting in increased drug clearance. There were no clinical responses; PD analysis showed biological activity of AZD1208.

conclusionsDespite the lack of single-agent clinical efficacy with AZD1208, PIM kinase inhibition may hold potential as an anticancer treatment, perhaps in combination with other agents.

Indexed as

AdultAgedAged, 80 and overBiphenyl CompoundsCytochrome P-450 CYP3AFemaleGene Expression Regulation, NeoplasticHematologic NeoplasmsHumansMaleMaximum Tolerated DoseMiddle AgedNeoplasmsProtein Kinase InhibitorsThiazolidinesUp-RegulationAZD1208Biphenyl CompoundsCYP3A4 protein, humanCytochrome P-450 CYP3AProtein Kinase InhibitorsThiazolidines

Identifiers

PMID29765150
PMCPMC5988656
OpenAlexW2803557794

What OpenQuestion holds

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Registered trials

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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.