Evidence map›Paper›PMID 28314838›Full record

Trial reportThe oncologist2017

A Phase I Study of Abiraterone Acetate Combined with BEZ235, a Dual PI3K/mTOR Inhibitor, in Metastatic Castration Resistant Prostate Cancer.

Xiao X Wei, Andrew C Hsieh, Won Kim, Terence Friedlander, Amy M Lin, Mirela Louttit, Charles J Ryan

Open access · bronzeAbstract readClinical Trial, Phase IRandomized Controlled Trial
In one paragraph

Trial report in The oncologist, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
5.1field-weighted citation impact, top 4% 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

36 citing papers in PubMed, 55 citations in OpenAlex.

  1. Phase Ib/II Study of Enzalutamide with Samotolisib (LY3023414) or Placebo in Patients with Metastatic Castration-Resistant Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022
    Trial
  2. Review
  3. Review
  4. Review
  5. Review
  6. Review
  7. Prostate cancer stem cells and their targeted therapies.Frontiers in cell and developmental biology · 2024
    Review
  8. Review
  9. Article
  10. Targeting Key Players of Neuroendocrine Differentiation in Prostate Cancer.International journal of molecular sciences · 2023
    Review
  11. From Translation to Treatment.Faculty reviews · 2023
    Review
  12. Review
  13. Review
  14. Review
  15. Review
  16. Article
  17. Review
  18. Targeting treatment options for castration-resistant prostate cancer.American journal of clinical and experimental urology · 2021
    Review
  19. Article
  20. 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

7 authors at 3 institutions in 1 country.

Xiao X WeiUniversity of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, California, USA xiao.wei@ucsf.edu.
Andrew C HsiehUniversity of Washington, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Won KimUniversity of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, California, USA.
Terence FriedlanderUniversity of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, California, USA.
Amy M LinUniversity of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, California, USA.
Mirela LouttitUniversity of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, California, USA.
Charles J RyanUniversity of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, California, USA.
UCSF Helen Diller Family Comprehensive Cancer Center · USUniversity of California, San Francisco · USUniversity of Washington · US

Funding

Defining the role of eIF4F in metastatic castration resistant prostate cancerK08CA175154 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HSIEH, ANDREW CALEB · 2013 to 2017
$890k
NCI NIH HHS K08 CA175154
6 · The paper itself

Abstract

lessons learnedThe combination of standard dose abiraterone acetate and BEZ235, a pan-class I PI3K and mTORC1/2 inhibitor, was poorly tolerated in men with progressive mCRPC.Although the clinical development of BEZ235 has been discontinued in prostate cancer, agents that more selectively target PI3K-AKT-mTOR signaling may have a more favorable therapeutic index and should continue to be explored.

backgroundAndrogen receptor (AR) and phosphatidylinositol-3 kinase (PI3K) signaling are two commonly perturbed pathways in prostate cancer. Preclinical data have shown that the two pathways compensate for each other when one is inhibited, and combined inhibition of AR and PI3K signaling may be a viable strategy to prevent or overcome castration resistance.

methodsThis phase I study evaluated the safety and tolerability of abiraterone acetate and prednisone combined with BEZ235, a dual PI3K and mTORC1/2 inhibitor, in men with progressive metastatic castration resistant prostate cancer (mCRPC) who have not received prior chemotherapy.

resultsSix patients (

conclusionThe combination of standard-dose abiraterone/prednisone with BEZ235 200 mg twice daily was poorly tolerated in patients with mCRPC. The on-target and off-target effects of dual PI3K and mTORC inhibition likely contributed to the unacceptable toxicity profile.

Indexed as

Abiraterone AcetateAgedAntineoplastic Combined Chemotherapy ProtocolsDrug-Related Side Effects and Adverse ReactionsHumansImidazolesMaleMiddle AgedPhosphoinositide-3 Kinase InhibitorsProstate-Specific AntigenProstatic Neoplasms, Castration-ResistantQuinolinesReceptors, AndrogenSignal TransductionTOR Serine-Threonine KinasesAbiraterone AcetateAR protein, humandactolisibImidazolesMTOR protein, humanPhosphoinositide-3 Kinase InhibitorsProstate-Specific AntigenQuinolinesReceptors, AndrogenTOR Serine-Threonine Kinases

Identifiers

PMID28314838
PMCPMC5423513
OpenAlexW2596939555

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.