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Phase II Study of Pseudomonas aeruginosa-Mannose-Sensitive Hemagglutinin in Combination with Capecitabine for Her-2–Negative Metastatic Breast Cancer Pretreated with Anthracycline and Taxane

PURPOSE: Metastatic breast cancer (MBC) remains an incurable disease despite major therapeutic advances. Pseudomonas aeruginosa–mannose-sensitive hemagglutinin (PA-MSHA) has been established to have anti-proliferative effects against breast cancer cells in preclinical experiments, and is indicated f...

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Autores principales: Lv, Fangfang, Cao, Jun, Liu, Zhebin, Wang, Zhonghua, Zhang, Jian, Zhang, Sheng, Wang, Leiping, Zhao, Xinmin, Shao, Zhimin, Wang, Biyun, Hu, Xichun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4359133/
https://www.ncbi.nlm.nih.gov/pubmed/25768439
http://dx.doi.org/10.1371/journal.pone.0118607
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author Lv, Fangfang
Cao, Jun
Liu, Zhebin
Wang, Zhonghua
Zhang, Jian
Zhang, Sheng
Wang, Leiping
Zhao, Xinmin
Shao, Zhimin
Wang, Biyun
Hu, Xichun
author_facet Lv, Fangfang
Cao, Jun
Liu, Zhebin
Wang, Zhonghua
Zhang, Jian
Zhang, Sheng
Wang, Leiping
Zhao, Xinmin
Shao, Zhimin
Wang, Biyun
Hu, Xichun
author_sort Lv, Fangfang
collection PubMed
description PURPOSE: Metastatic breast cancer (MBC) remains an incurable disease despite major therapeutic advances. Pseudomonas aeruginosa–mannose-sensitive hemagglutinin (PA-MSHA) has been established to have anti-proliferative effects against breast cancer cells in preclinical experiments, and is indicated for treatment of cancer in China. We performed a phase II trial combining PA-MSHA with capecitabine in patients with heavily pretreated MBC. METHODS: Eligibility criteria included human epidermal growth factor receptor 2–negative MBC, prior therapy with anthracyclines and taxanes, at least one prior chemotherapy regimen for metastatic disease or early relapse after a taxane plus anthracycline adjuvant regimen, and adequate organ function and performance status. PA-MSHA 1 mg was administered subcutaneously every other day and capecitabine 1000 mg/m(2) orally twice a day for 2 weeks on, 1 week off. The primary end point was progression-free survival. RESULTS: A total of 97 patients were enrolled. Median progression-free survival (PFS) was 4.0 months [95 % confidence interval (CI) 3.0–4.9], which was not significantly different from that in historical controls. However, median PFS was significantly longer (8.2 months; 95 % CI 6.7–9.7) in 24 patients with moderate immune-related adverse events (irAEs) such as fever or skin induration at the injection site than in those with no or mild irAEs (3.1 months, 95 % CI 2.5–3.6; p = 0.003). Overall survival was also improved in these patients (25.4 vs. 16.4 months; p = 0.044). PA-MSHA has a good safety profile, with only 6 patients (6.2 %) discontinuing treatment. PA-MSHA did not increase capecitabine-related toxicities such as hand-foot syndrome, nausea, and vomiting. CONCLUSION: Adding PA-MSHA to capecitabine has a good safety profile in patients with heavily pre-treated MBC, although benefit from this regimen might occur only in patients with moderate PA-MSHA–related adverse events. TRIAL REGISTRATION: ClinicalTrials.gov NCT01380808
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spelling pubmed-43591332015-03-23 Phase II Study of Pseudomonas aeruginosa-Mannose-Sensitive Hemagglutinin in Combination with Capecitabine for Her-2–Negative Metastatic Breast Cancer Pretreated with Anthracycline and Taxane Lv, Fangfang Cao, Jun Liu, Zhebin Wang, Zhonghua Zhang, Jian Zhang, Sheng Wang, Leiping Zhao, Xinmin Shao, Zhimin Wang, Biyun Hu, Xichun PLoS One Research Article PURPOSE: Metastatic breast cancer (MBC) remains an incurable disease despite major therapeutic advances. Pseudomonas aeruginosa–mannose-sensitive hemagglutinin (PA-MSHA) has been established to have anti-proliferative effects against breast cancer cells in preclinical experiments, and is indicated for treatment of cancer in China. We performed a phase II trial combining PA-MSHA with capecitabine in patients with heavily pretreated MBC. METHODS: Eligibility criteria included human epidermal growth factor receptor 2–negative MBC, prior therapy with anthracyclines and taxanes, at least one prior chemotherapy regimen for metastatic disease or early relapse after a taxane plus anthracycline adjuvant regimen, and adequate organ function and performance status. PA-MSHA 1 mg was administered subcutaneously every other day and capecitabine 1000 mg/m(2) orally twice a day for 2 weeks on, 1 week off. The primary end point was progression-free survival. RESULTS: A total of 97 patients were enrolled. Median progression-free survival (PFS) was 4.0 months [95 % confidence interval (CI) 3.0–4.9], which was not significantly different from that in historical controls. However, median PFS was significantly longer (8.2 months; 95 % CI 6.7–9.7) in 24 patients with moderate immune-related adverse events (irAEs) such as fever or skin induration at the injection site than in those with no or mild irAEs (3.1 months, 95 % CI 2.5–3.6; p = 0.003). Overall survival was also improved in these patients (25.4 vs. 16.4 months; p = 0.044). PA-MSHA has a good safety profile, with only 6 patients (6.2 %) discontinuing treatment. PA-MSHA did not increase capecitabine-related toxicities such as hand-foot syndrome, nausea, and vomiting. CONCLUSION: Adding PA-MSHA to capecitabine has a good safety profile in patients with heavily pre-treated MBC, although benefit from this regimen might occur only in patients with moderate PA-MSHA–related adverse events. TRIAL REGISTRATION: ClinicalTrials.gov NCT01380808 Public Library of Science 2015-03-13 /pmc/articles/PMC4359133/ /pubmed/25768439 http://dx.doi.org/10.1371/journal.pone.0118607 Text en © 2015 Lv et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Lv, Fangfang
Cao, Jun
Liu, Zhebin
Wang, Zhonghua
Zhang, Jian
Zhang, Sheng
Wang, Leiping
Zhao, Xinmin
Shao, Zhimin
Wang, Biyun
Hu, Xichun
Phase II Study of Pseudomonas aeruginosa-Mannose-Sensitive Hemagglutinin in Combination with Capecitabine for Her-2–Negative Metastatic Breast Cancer Pretreated with Anthracycline and Taxane
title Phase II Study of Pseudomonas aeruginosa-Mannose-Sensitive Hemagglutinin in Combination with Capecitabine for Her-2–Negative Metastatic Breast Cancer Pretreated with Anthracycline and Taxane
title_full Phase II Study of Pseudomonas aeruginosa-Mannose-Sensitive Hemagglutinin in Combination with Capecitabine for Her-2–Negative Metastatic Breast Cancer Pretreated with Anthracycline and Taxane
title_fullStr Phase II Study of Pseudomonas aeruginosa-Mannose-Sensitive Hemagglutinin in Combination with Capecitabine for Her-2–Negative Metastatic Breast Cancer Pretreated with Anthracycline and Taxane
title_full_unstemmed Phase II Study of Pseudomonas aeruginosa-Mannose-Sensitive Hemagglutinin in Combination with Capecitabine for Her-2–Negative Metastatic Breast Cancer Pretreated with Anthracycline and Taxane
title_short Phase II Study of Pseudomonas aeruginosa-Mannose-Sensitive Hemagglutinin in Combination with Capecitabine for Her-2–Negative Metastatic Breast Cancer Pretreated with Anthracycline and Taxane
title_sort phase ii study of pseudomonas aeruginosa-mannose-sensitive hemagglutinin in combination with capecitabine for her-2–negative metastatic breast cancer pretreated with anthracycline and taxane
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4359133/
https://www.ncbi.nlm.nih.gov/pubmed/25768439
http://dx.doi.org/10.1371/journal.pone.0118607
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