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A phase II study of epirubicin, cisplatin and capecitabine as neoadjuvant chemotherapy in locally advanced or inflammatory breast cancer
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology. (Bröstgruppen)
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2007 (English)In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 43, no 7, 1153-1160 p.Article in journal (Refereed) Published
Abstract [en]

Aim: To assess the efficacy and safety of epirubicin, capecitabine and cisplatin (EXC) combination therapy in locally advanced breast cancer (LABC) and investigate the predictive value of selected biomarkers. Methods: Newly diagnosed LABC patients received four 3-weekly cycles of neoadjuvant EXC (epirubicin 60 mg/m2 day 1; capecitabine 1000 mg/m2 bid, days 1-14; cisplatin 60 mg/m2day 1) and two cycles of post-operative EXC. Results: Eight (17%) of 48 patients had inflammatory breast cancer. Overall response rate was 74% (95% CI: 59-86%), including complete responses in 13% (95% CI: 5-26%). Nine (22%; 95% CI: 11-38%) of 41 patients undergoing surgery achieved pathologic complete response (pCR), giving a pCR rate of 19% (95% CI: 9-33%) in the intent-to-treat population. Haematological toxicity was manageable. The most problematic toxicities were chemotherapy-induced nausea/vomiting and hypercoagulative disorders. None of the biomarkers investigated, including HER2, predicted response. Conclusion: EXC showed high efficacy in LABC, with high clinical response and pCR rate. Nausea and vomiting were unexpectedly frequent, and more aggressive prophylaxis and management of these side effects is recommended in future studies of this combination.

Place, publisher, year, edition, pages
2007. Vol. 43, no 7, 1153-1160 p.
Keyword [en]
Epirubicin, Cisplatin, Capecitabine, Breast cancer, Neoadjuvant, Phase II, Clinical trial, Biomarker, Pathologic complete response
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-95414DOI: 10.1016/j.ejca.2007.02.002ISI: 000246605100015PubMedID: 17398088OAI: oai:DiVA.org:uu-95414DiVA: diva2:169608
Available from: 2007-02-02 Created: 2007-02-02 Last updated: 2011-02-01Bibliographically approved
In thesis
1. Chemosensitivity in Breast Cancer
Open this publication in new window or tab >>Chemosensitivity in Breast Cancer
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Breast cancer mortality in Sweden is now in decline, thanks to early detection and the wide use of adjuvant endocrine therapy and chemotherapy.

While hormone receptor status is predictive of response to endocrine treatment, there is no clinically useful predictive marker of a patient’s response to chemotherapy. Consequently, patients receive chemotherapy with considerable toxicity but minimal benefit. The aim of this thesis was to investigate a number of methods with the potential to predict response to chemotherapy and thus enhance treatment efficacy in breast cancer patients.

We found that topo IIα, the key target enzyme of topo II inhibitors, is significantly expressed in nonproliferating breast cancer cells. This finding may explain why topo II inhibitors are effective in patients with slow growing tumors and a low proliferation rate.

Topo IIα gene amplification was suggestive of increased response to anthracyclines in advanced breast cancer, whereas the oncogene HER2 had no predictive value by itself. These findings are in accordance with current knowledge.

Cyclin A, a marker of cell proliferation, showed good prognostic value but did not predict response to chemotherapy in advanced breast cancer.

In vitro chemosensitivity testing with FMCA predicted tumor response in patients with advanced breast cancer with a sensitivity of 89% and a specificity of 53%. Our results are consistent with the results from similar assays, which predict drug resistance with good accuracy while clinical drug sensitivity is less reliably predicted. The use of FMCA and similar assays is not yet recommended outside clinical trials; their main utility is in preclinical testing of new anti-cancer drugs, including targeted therapies.

The combination of epirubicin, capecitabine, and cisplatin (EXC) demonstrated high clinical response rate (74%) and pathological complete response rate (22%) in locally advanced breast cancer, but with cumbersome toxicity. The fluoropyrimidine biomarkers TS, TP, and DPD did not predict response to the EXC regimen.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2007. 83 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 221
Oncology, breast cancer, chemotherapy, anthracycline, predictive, topoisomerase, TOP2A, HER2, cyclin A, in vitro, Onkologi
urn:nbn:se:uu:diva-7459 (URN)978-91-554-6787-6 (ISBN)
Public defence
2007-02-23, Wilandersalen, M-huset, Universitetssjukhuset, Örebro, 13:15
Available from: 2007-02-02 Created: 2007-02-02Bibliographically approved

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Villman, KennethBlomqvist, CarlAhlgren, Johan
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OncologyDepartment of Oncology, Radiology and Clinical ImmunologyDepartment of Genetics and PathologyCentre for Research and Development, Gävleborg
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