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Use of the Peroxisome Proliferator-Activated Receptor (PPAR) γ Ligand Troglitazone as Treatment for Refractory Breast Cancer: A Phase II Study
Abstract
Purpose To evaluate the therapeutic effects of the peroxisome proliferator-activated receptor (PPAR) gamma activating ligand, troglitazone, in patients with refractory metastatic breast cancer.Experimental design Patients with advanced breast cancer refractory to at least one chemotherapy regimen (ER negative tumors) or two hormonal regimens (ER positive tumors) were treated with troglitazone at 800 mg p.o. QD until disease progression, to determine the percentage of patients free of progression at 6 months. Tumor response, toxicity, and changes in serum tumor markers (CEA, CA27.29) that might reflect alteration in tumor differentiation, were also examined.Results Twenty-two patients were enrolled before suspension of protocol accrual and treatment when troglitazone was withdrawn from commercial availability following FDA warnings on hepatic toxicity. No objective responses (CR or PR) were observed; only three patients had SD at 8 weeks. Patients came off study for PD (16), DLT (1), FDA withdrawal (2), or other (3) reasons. No patients took troglitazone for more than 20 weeks; all had experienced disease progression or began other systemic therapy within 6 months. All patients with elevated serum tumor markers (CEA and CA27.29) at baseline had rising tumor markers within 8 weeks.Conclusions While clinical trials among different patient populations might uncover subtle effects on tumor differentiation, PPARgamma activation by troglitazone has little apparent clinical value among patients with treatment-refractory metastatic breast cancer.
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“Only a few clinical trials of TZDs for cancer treatment have been conducted, and results have largely been negative (108).”
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Metadata
- Authors
- Burstein, H. J., Demetri, G. D., Mueller, E., Sarraf, P., Spiegelman, B. M., & Winer, E. P.
- Affiliations
- Dana-Farber Cancer Institute (US)
- Brigham and Women's Hospital (US)
- Venue
- Breast Cancer Research and Treatment
- Published
- 2003-06
- Volume
- 79
- Issue
- 3
- Pages
- 391-397
- ISSN
- 0167-6806 (ISSN-L)
- 1573-7217
- OpenAlex
- W1968980738
- Cited by
- 228
- References
- 21
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 5 · 2023: 4 · 2022: 4 · 2021: 14 · 2020: 5 · 2019: 7 · 2018: 13 · 2017: 11 · 2016: 5 · 2015: 3 · 2014: 4 · 2013: 10 · 2012: 18
- FWCI
- 4.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Breast Cancer Research and Treatment (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- troglitazone, PPARγ agonists, metastatic breast cancer, estrogen receptor-negative breast cancer, estrogen receptor-positive breast cancer, tumor markers, CEA, CA 27.29, tumor differentiation, drug toxicity, disease progression
- MeSH terms
- Troglitazone, Administration, Oral, Adult, Aged, Antineoplastic Agents, Breast Neoplasms, Chromans, Female, Humans, Liver, Middle Aged, Neoplasm Invasiveness, Thiazoles, Treatment Outcome, Disease Progression, Thiazolidinediones
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