Tipifarnib Plus Tamoxifen in Tamoxifen-Resistant Metastatic Breast Cancer: A Negative Phase II and Screening of Potential Therapeutic Markers by Proteomic Analysis
| Autor: | Henri Roché, Gilles Favre, Odile Schiltz, Bernard Monsarrat, Emilie Malissein, Karima Chaoui, Ben Allal, Florence Dalenc, Sabrina Marsili, Valérie Lauwers-Cances, Elise Meunier, Sophie F. Doisneau-Sixou, Nicole Renée, Thomas Filleron |
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| Rok vydání: | 2010 |
| Předmět: |
Adult
Oncology Cancer Research medicine.medical_specialty Neoplasms Hormone-Dependent Protein Array Analysis Breast Neoplasms Quinolones Breast cancer Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Farnesyltranstransferase Humans Neoplasm Metastasis Aged business.industry Cancer Middle Aged Antiestrogen medicine.disease Metastatic breast cancer Postmenopause Tamoxifen Drug Resistance Neoplasm Selective estrogen receptor modulator Immunology Female Tipifarnib Breast disease business medicine.drug |
| Zdroj: | Clinical Cancer Research. 16:1264-1271 |
| ISSN: | 1557-3265 1078-0432 |
| Popis: | Purpose: Tipifarnib, a farnesyltransferase inhibitor, has antitumor activity in heavily pretreated metastatic breast cancer patients. Preclinical data suggest that FTIs could restore tamoxifen responsiveness in tamoxifen-resistant disease. Thus, combining FTIs and tamoxifen may be a promising clinical approach after relapse or progression on tamoxifen. Experimental Design: Postmenopausal patients with measurable estrogen receptor– and/or progesterone receptor–expressing metastatic breast cancers were enrolled. Only patients with disease progression on tamoxifen were eligible, but there was no limitation regarding prior chemotherapy or hormone therapy regimens. Patients were immediately treated with 300 mg (n = 12) or 200 mg (n = 10) tipifarnib twice daily for 21 of 28-day cycles plus tamoxifen once daily. Serum was collected at baseline and after 8 weeks of treatment to enable proteomic comparison and identify possible predictive response markers. Results: Twenty patients were enrolled and evaluated for efficacy: one patient had an objective response (liver metastasis) and nine had stable disease after 6 months for a clinical benefit rate of 50%; median duration of benefit was 10.3 (range, 7.4-20.2) months. The proteomic analysis by SELDI-TOF and LTQ-FT-Orbitrap identified a known peptide of fibrinogen α, the intensity of which was significantly increased in patients with progression compared with patients who benefited from the combined treatment after 8 weeks. Conclusions: Because the primary end point of efficacy (three objective responses) was not achieved, the study is negative. Nevertheless, the identified peptide could be of interest in discriminating, at 8 weeks of treatment, responders from nonresponders. Clin Cancer Res; 16(4); 1264–71 |
| Databáze: | OpenAIRE |
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