↓ Skip to main content

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

Overview of attention for article published in Breast Cancer Research and Treatment, December 2011
Altmetric Badge

Mentioned by

twitter
1 tweeter

Citations

dimensions_citation
48 Dimensions

Readers on

mendeley
38 Mendeley
Title
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
Published in
Breast Cancer Research and Treatment, December 2011
DOI 10.1007/s10549-011-1928-x
Pubmed ID
Authors

B. Ramaswamy, 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

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.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 38 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 38 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 7 18%
Researcher 6 16%
Other 5 13%
Student > Master 5 13%
Student > Ph. D. Student 4 11%
Other 11 29%
Readers by discipline Count As %
Medicine and Dentistry 13 34%
Biochemistry, Genetics and Molecular Biology 10 26%
Agricultural and Biological Sciences 5 13%
Mathematics 2 5%
Unspecified 2 5%
Other 6 16%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 28 December 2011.
All research outputs
#10,931,949
of 12,334,049 outputs
Outputs from Breast Cancer Research and Treatment
#2,753
of 3,102 outputs
Outputs of similar age
#204,357
of 239,243 outputs
Outputs of similar age from Breast Cancer Research and Treatment
#81
of 88 outputs
Altmetric has tracked 12,334,049 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 3,102 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.2. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 239,243 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 88 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.