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Cited by 424HER2/EGFR in Cancer ResearchHeat shock proteins researchGastric Cancer Management and Outcomes

The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.

HSP90 Inhibition Is Effective in Breast Cancer: A Phase II Trial of Tanespimycin (17-AAG) Plus Trastuzumab in Patients with HER2-Positive Metastatic Breast Cancer Progressing on Trastuzumab

Modi, Shanu, Stopeck, Alison, Linden, Hannah, Solit, David, Chandarlapaty, Sarat, Rosen, Neal, D'Andrea, Gabriella, Dickler, Maura, Moynahan, Mary E., Sugarman, Steven, Ma, Weining, Patil, Sujata, Norton, Larry, Hannah, Alison L., Hudis, Clifford·2011·Clinical Cancer Research
DOI 10.1158/1078-0432.ccr-11-0072

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Abstract

PURPOSE: HSP90 is a chaperone protein required for the stability of a variety of client proteins. 17-Demethoxygeldanamycin (17-AAG) is a natural product that binds to HSP90 and inhibits its activity, thereby inducing the degradation of these clients. In preclinical studies, HER2 is one of the most sensitive known client proteins of 17-AAG. On the basis of these data and activity in a phase I study, we conducted a phase II study of 17-AAG (tanespimycin) with trastuzumab in advanced trastuzumab-refractory HER2-positive breast cancer. EXPERIMENTAL DESIGN: We enrolled patients with metastatic HER2(+) breast cancer whose disease had previously progressed on trastuzumab. All patients received weekly treatment with tanespimycin at 450 mg/m(2) intravenously and trastuzumab at a conventional dose. Therapy was continued until disease progression. The primary endpoint was response rate by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. RESULTS: Thirty-one patients were enrolled with a median age of 53 years and a median Karnofsky performance status (KPS) of 90%. The most common toxicities, largely grade 1, were diarrhea, fatigue, nausea, and headache. The overall response rate was 22%, the clinical benefit rate [complete response + partial response + stable disease] was 59%, the median progression-free survival was 6 months (95% CI: 4-9), and the median overall survival was 17 months (95% CI: 16-28). CONCLUSIONS: This is the first phase II study to definitively show RECIST-defined responses for 17-AAG in solid tumors. Tanespimycin plus trastuzumab has significant anticancer activity in patients with HER2-positive, metastatic breast cancer previously progressing on trastuzumab. Further research exploring this therapeutic interaction and the activity of HSP90 inhibitors is clearly warranted.

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Crossref · 10.1158/1078-0432.ccr-11-0072

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Metadata

Authors
Modi, S., Stopeck, A., Linden, H., Solit, D., Chandarlapaty, S., Rosen, N., D'Andrea, G., Dickler, M., Moynahan, M. E., Sugarman, S., Ma, W., Patil, S., Norton, L., Hannah, A. L., & Hudis, C.
Affiliations
  • Memorial Sloan Kettering Cancer Center (US)
  • Authors' Affiliations: 1Memorial Sloan-Kettering Cancer Center, New York, New York; 2Arizona Cancer Center, Tucson, Arizona; 3University of Washington, Seattle, Washington; and 4Kosan Biosciences/Bristol-Myers Squibb, Hayward, California
ORCID
Venue
Clinical Cancer Research
Publisher
American Association for Cancer Research (AACR)
Published
2011-07-31
Volume
17
Issue
15
Pages
5132-5139
ISSN
  • 1078-0432 (ISSN-L)
  • 1557-3265
DOI
10.1158/1078-0432.ccr-11-0072
OpenAlex
W2171708713
Cited by
424
References
45
Citations by year
2026: 12 · 2025: 15 · 2024: 7 · 2023: 13 · 2022: 21 · 2021: 14 · 2020: 24 · 2019: 21 · 2018: 14 · 2017: 27 · 2016: 32 · 2015: 43 · 2014: 52 · 2013: 55 · 2012: 51
FWCI
28.33
Type
journal article
Language
en
Open access
closed
Locations
  • Clinical Cancer Research (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
  • Health Sciences › Medicine › Oncology › Gastric Cancer Management and Outcomes
Keywords
HSP90 inhibition, tanespimycin, 17-AAG, trastuzumab, HER2-positive breast cancer, metastatic breast cancer, trastuzumab-refractory disease, combination therapy, Hsp90 client proteins, HER2 degradation, response rate, progression-free survival, overall survival
MeSH terms
Trastuzumab, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols, Breast Neoplasms, Female, Humans, Male, Middle Aged, Neoplasm Metastasis, Benzoquinones, Breast Neoplasms, Male, Disease-Free Survival, Genes, erbB-2, HSP90 Heat-Shock Proteins, Retreatment, Lactams, Macrocyclic, Antibodies, Monoclonal, Humanized

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