Evidence map›Paper›PMID 25920479›Full record

ArticleInvestigational new drugs2015

AZD3514, an oral selective androgen receptor down-regulator in patients with castration-resistant prostate cancer - results of two parallel first-in-human phase I studies.

A Omlin, R J Jones, R van der Noll, T Satoh, M Niwakawa, S A Smith, J Graham, M Ong, R D Finkelman, J H M Schellens and 15 more

Abstract readClinical Trial, Phase IMulticenter Study
PubMed Publisher
In one paragraph

Article in Investigational new drugs, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
–field-weighted citation impact
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

30 citing papers in PubMed.

  1. Review
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  4. Targeted protein degradation: mechanisms, strategies and application.Signal transduction and targeted therapy · 2022
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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

25 authors.

A OmlinProstate Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Downs Road, Sutton, Surrey, UK.
R J Jones
R van der Noll
T Satoh
M Niwakawa
S A Smith
J Graham
M Ong
R D Finkelman
J H M Schellens
A Zivi
M Crespo
R Riisnaes
D Nava-Rodrigues
M D Malone
C Dive
R Sloane
D Moore
J J Alumkal
A Dymond
P A Dickinson
M Ranson
G Clack
J de Bono
T Elliott

Funding

Cancer Research UK 19278
6 · The paper itself

Abstract

backgroundAZD3514 is a first-in-class, orally bio-available, androgen-dependent and -independent androgen receptor inhibitor and selective androgen-receptor down-regulator (SARD).

methodsIn study 1 and 2, castration-resistant prostate cancer (CRPC) patients (pts) were initially recruited into a once daily (QD) oral schedule (A). In study 1, pharmacokinetic assessments led to twice daily (BID) dosing (schedule B) to increase exposure. Study 2 explored a once daily schedule.

resultsIn study 1, 49 pts were treated with escalating doses of AZD3514 (A 35 pts, B 14 pts). Starting doses were 100 mg (A) and 1000 mg (B). The AZD3514 formulation was switched from capsules to tablets at 1000 mg QD. 2000 mg BID was considered non-tolerable due to grade (G) 2 toxicities (nausea [N], vomiting [V]). No adverse events (AEs) met the dose-limiting toxicity (DLT) definition. Thirteen pts received AZD3514 in study 2, with starting doses of 250 mg QD. The most frequent drug-related AEs were N: G1/2 in 55/70 pts (79 %); G3 in 1 pt (1.4 %); & V: G1/2 in 34/70 pts (49 %) & G3 in 1 pt (1.4 %). PSA declines (≥50 %) were documented in 9/70 patients (13 %). Objective soft tissue responses per RECIST1.1 were observed in 4/24 (17 %) pts in study 1.

conclusionAZD3514 has moderate anti-tumour activity in pts with advanced CRPC but with significant levels of nausea and vomiting. However, anti-tumour activity as judged by significant PSA declines, objective responses and durable disease stabilisations, provides the rationale for future development of SARD compounds.

Indexed as

Down-RegulationAdministration, OralAgedAged, 80 and overAntineoplastic AgentsDose-Response Relationship, DrugHumansMaleMiddle AgedNeoplastic Cells, CirculatingProstate-Specific AntigenProstatic Neoplasms, Castration-ResistantPyridazinesRadiographyReceptors, AndrogenAntineoplastic AgentsAR protein, humanAZD3514Prostate-Specific AntigenPyridazinesReceptors, Androgen

Identifiers

PMID25920479

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.