Evidence map›Paper›PMID 22200869›Full record

Trial reportBreast cancer research and treatment2012

Phase I-II study of vorinostat plus paclitaxel and bevacizumab in metastatic breast cancer: evidence for vorinostat-induced tubulin acetylation and Hsp90 inhibition in vivo.

B Ramaswamy, W Fiskus, B Cohen, C Pellegrino, D L Hershman, E Chuang, Thehang Luu, G Somlo, M Goetz, R Swaby and 6 more

Registry-linked trialOpen access · greenAbstract readClinical Trial, Phase IClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Breast cancer research and treatment, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00368875 (Phase I/II Study of a Combination of Suberoylanilide Hydroxamic Acid), which is not on this map. Cited by 44 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed, 1 pooled it
3.9field-weighted citation impact, top 6% 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.

NCT00368875 phase1 / phase2completednot on this map

Phase I/II Study of a Combination of Suberoylanilide Hydroxamic Acid (Vorinostat) Plus Paclitaxel and Bevacizumab in Patients With Advanced Metastatic and/or Local Chest Wall Recurrent Breast Cancer

TypeinterventionalSponsorNational Cancer Institute (NCI)Ran2006 to 2011Enrolled54ConditionsMale Breast Cancer, Stage IIIB Breast Cancer, Stage IIIC Breast Cancer, Stage IV Breast CancerArmsvorinostat, paclitaxel, bevacizumab
3 · Its place in the literature

Who cites it

44 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.

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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

16 authors at 10 institutions in 1 country.

B RamaswamyThe Ohio State University, Columbus, OH, USA. Bhuvaneswari.ramaswamy@osumc.edu
W Fiskus
B Cohen
C Pellegrino
D L Hershman
E Chuang
Thehang Luu
G Somlo
M Goetz
R Swaby
C L Shapiro
V Stearns
P Christos
I Espinoza-Delgado
K Bhalla
J A Sparano
City Of Hope National Medical Center · USCornell University · USMontefiore Medical Center · USThe Ohio State University · USThe University of Kansas Cancer Center · USAlbert Einstein College of Medicine · USFox Chase Cancer Center · USMayo Clinic in Arizona · USNewYork–Presbyterian Hospital · USSidney Kimmel Cancer Center · US

Funding

TAS:: 75 0850 ::TAS RECOVERY ACT - ACTNOW CLINICAL TRIAL 8288N01CM62205 · NCI · MAYO CLINIC ROCHESTER · PI ERLICHMAN, CHARLES · 2007 to 2011
$8.0M
NCI NIH HHS N01 CM062204NCI NIH HHS N01 CM062205NCI NIH HHS N01 CM062207NCI NIH HHS N01-CM-62204NCI NIH HHS N01 CM62205NCI NIH HHS N01-CM-62207
6 · The paper itself

Abstract

In preclinical models, the histone deacetylase inhibitor vorinostat sensitizes breast cancer cells to tubulin-polymerizing agents and to anti-vascular endothelial growth factor-directed therapies. We sought to determine the safety and efficacy of vorinostat plus paclitaxel and bevacizumab as first-line therapy in metastatic breast cancer (MBC), and the biological effects of vorinostat in vivo. For this purpose of this study, 54 patients with measurable disease and no prior chemotherapy for MBC received vorinostat (200 or 300 mg PO BID) on days 1-3, 8-10, and 15-17, plus paclitaxel (90 mg/m(2)) on days 2, 9, 16, and bevacizumab (10 mg/kg) on days 2 and 16 every 28 days. The primary objective of the phase I study was to determine the recommended phase II dose (RPTD) of vorinostat, and for the phase II to detect an improvement of response rate from 40 to 60% (alpha = 0.10, beta = 0.10). No dose limiting toxicities were observed, and the RPTD of vorinostat was 300 mg BID. For the primary efficacy analysis in 44 patients at the RPTD, we observed 24 objective responses (55%, 95% confidence intervals (C.I) 39%, 70%). The adverse event profile was consistent with paclitaxel-bevacizumab, with the exception of increased diarrhea with the addition of vorinostat. Analysis of serial tumor biopsies in seven patients showed increased acetylation of Hsp90 and α-tubulin following vorinostat. Vorinostat induces histone and alpha tubulin acetylation and functional inhibition of Hsp90 in breast cancer in vivo and can be safely combined with paclitaxel and bevacizumab.

Indexed as

AcetylationAdultAgedAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBevacizumabBiomarkers, TumorBreast NeoplasmsDisease-Free SurvivalFemaleHSP90 Heat-Shock ProteinsHumansHydroxamic AcidsKaplan-Meier EstimateLiver NeoplasmsLung NeoplasmsAntibodies, Monoclonal, HumanizedBevacizumabBiomarkers, TumorHSP90 Heat-Shock ProteinsHydroxamic AcidsPaclitaxelTubulinVorinostat

Identifiers

PMID22200869
PMCPMC3486521
OpenAlexW2167292948

What OpenQuestion holds

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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.