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Tuesday, June 27th, 2017
Table of Contents

1 Introduction
5 PMID
 [F] Diseases Research  / PubMed Research Articles  /
A Phase I/II study of suberoylanilide hydroxamic acid (SAHA) in combination with trastuzumab (Herceptin) in patients with advanced metastatic and/or local chest wall recurrent HER2-amplified breast cancer: a trial of the ECOG-ACRIN Cancer Research Group (E1104).

PubMed

 

Resource

Breast cancer research and treatment 2017 Jun 17; ()

Authors

Goldstein LJ1; Zhao F2; Wang M3; Swaby RF4; Sparano JA5; Meropol NJ6; Bhalla KN7; Pellegrino CM8; Katherine Alpaugh R9; Falkson CI10; Klein P11; Sledge GW12;

Author Information
  • 1Fox Chase Cancer Center, Philadelphia, PA, USA. lori.goldstein@fccc.edu.
  • 2Dana Farber Cancer Institute - ECOG-ACRIN Biostatistics Center, Boston, MA, USA.
  • 3Dana Farber Cancer Institute - ECOG-ACRIN Biostatistics Center, Boston, MA, USA.
  • 4Fox Chase Cancer Center, Philadelphia, PA, USA.
  • 5West Chester Medical Center, Valhalla, NY, USA.
  • 6Fox Chase Cancer Center, Philadelphia, PA, USA.
  • 7MD Anderson Cancer Center, Houston, TX, USA.
  • 8West Chester Medical Center, Valhalla, NY, USA.
  • 9Fox Chase Cancer Center, Philadelphia, PA, USA.
  • 10University of Alabama, Birmingham, AL, England, UK.
  • 11Beth Israel Medical Center, New York, USA.
  • 12Stanford University, Stanford, CA, USA.

Abstract

PURPOSE: Suberoylanilide hydroxamic acid (SAHA; vorinostat), a small molecule inhibitor of histone deacetylase, attenuates signaling pathways known to confer trastuzumab resistance. A combination of SAHA and trastuzumab may be a promising strategy to improve the efficacy of trastuzumab against breast cancer. In this Phase I/II study, we evaluated the toxicity and response rate after treatment with SAHA and trastuzumab in patients with HER2-overexpressing metastatic breast cancer with trastuzumab-resistant progressive disease.

METHODS: In Phase I, the SAHA dose was modified in cohorts of 3-6 patients to find the dose level at which 0 or 1 patients experienced a dose-limiting toxicity (DLT) during the first cycle of therapy. In the Phase II study, response to the recommended dose identified in Phase I was based on the response evaluation criteria in solid tumors. Overall survival and time to progression were also evaluated.

RESULTS: The recommended dose was determined to be 200 mg twice a day on days 1-14 and IV trastuzumab 6 mg/kg on day 1 of a 21-day cycle (n = 6). The Phase II study (n = 10) was terminated when the pre-planned efficacy evaluation found that none of the patients in the primary analysis set responded to combination SAHA and trastuzumab treatment.

CONCLUSIONS: In patients with HER2-positive metastatic breast cancer who had relapsed or progressed during trastuzumab therapy, we observed no DLTs with SAHA 200 mg twice daily combined with trastuzumab; however, there was insufficient statistical evidence that adding SAHA reversed trastuzumab resistance in these patients.



PMID

28623430

Others

Publication Type: Journal Article


This article is licensed under the the National Library of Medicine License. It uses material from the PubMed National Library of Medicine Data.


Last Modified:   2016-03-27


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