Metastatic breast cancer patients treated with low-dose metronomic chemotherapy with cyclophosphamide and celecoxib: clinical outcomes and biomarkers of response

Background Preclinical results showing therapeutic effect and low toxicity of metronomic chemotherapy with cyclophosphamide (Cy) + celecoxib (Cel) for mammary tumors encouraged its translation to the clinic for treating advanced breast cancer patients (ABCP). Patients and methods A single-arm, mo...

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Autores principales: Perroud, Herman A, Alasino, Carlos María , Rico, María José, Mainetti, Leandro Ernesto, Queralt, Francisco , Pezzotto, Stella Maris, Rozados, Viviana R., Scharovsky, O. Graciela
Formato: article artículo acceptedVersion
Lenguaje:Inglés
Publicado: Springer 2018
Materias:
Angiogenesis 
Biomarkers 
Cyclophosphamide 
Celecoxib 
Metronomic chemotherapy 
Acceso en línea:http://hdl.handle.net/2133/11096
http://hdl.handle.net/2133/11096
Aporte de:
Repositorio Hipermedial de la Universidad Nacional de Rosario (UNR) de Universidad Nacional de Rosario
id I15-R121-2133-11096
record_format dspace
institution Universidad Nacional de Rosario
institution_str I-15
repository_str R-121
collection Repositorio Hipermedial de la Universidad Nacional de Rosario (UNR)
language Inglés
orig_language_str_mv eng
topic Angiogenesis 
Biomarkers 
Cyclophosphamide 
Celecoxib 
Metronomic chemotherapy 
spellingShingle Angiogenesis 
Biomarkers 
Cyclophosphamide 
Celecoxib 
Metronomic chemotherapy 
Perroud, Herman A
Alasino, Carlos María 
Rico, María José
Mainetti, Leandro Ernesto
Queralt, Francisco 
Pezzotto, Stella Maris
Rozados, Viviana R.
Scharovsky, O. Graciela
Metastatic breast cancer patients treated with low-dose metronomic chemotherapy with cyclophosphamide and celecoxib: clinical outcomes and biomarkers of response
topic_facet Angiogenesis 
Biomarkers 
Cyclophosphamide 
Celecoxib 
Metronomic chemotherapy 
description Background Preclinical results showing therapeutic effect and low toxicity of metronomic chemotherapy with cyclophosphamide (Cy) + celecoxib (Cel) for mammary tumors encouraged its translation to the clinic for treating advanced breast cancer patients (ABCP). Patients and methods A single-arm, mono-institutional, non-randomized, phase II, two-step clinical trial (approved by Bioethics Committee and Argentine Regulatory Authority) was designed. Patients received Cy (50 mg po.d) + Cel (200 mg p.o.bid). Patient eligibility criteria included: ABCP who progressed to anthracyclines, taxanes and capecitabine, ≤4 chemotherapy schemes, with good performance status. Several pro- and anti-angiogenic molecules and cells were determined as biomarkers. Informed consent was signed by all patients. Primary endpoint was clinical benefit (CB). Results Twenty patients were enrolled. Main clinical outcomes were prolonged disease stabilization and partial remission in 10/20 and 1/20 patients, respectively. CB was 55 %, and time to progression (TTP) was 21.1 weeks. Median TTP in patients who achieved CB was 35.6 weeks, and mean overall survival was 44.20 weeks. There were no grade 3/4 toxicities associated with treatment. Circulating endothelial cells (CECs) increased at the time of progression in patients who showed CB (P = 0.014). Baseline CECs and circulating endothelial progenitor cells showed marginal associations with TTP. Serum VEGF decreased (P = 0.050), sVEGFR-2 increased (P = 0.005) and VEGF/sVEGFR-2 ratio decreased during treatment (P = 0.041); baseline VEGF and VEGF/sVEGFR-2 were associated with TTP (P = 0.035 and P = 0.030, respectively), while sVEGFR-2 did not. Conclusions Treatment was effective, showing low toxicity profile and excellent tolerability. The combination had anti-angiogenic effect. Increased levels of CEC could be useful for detecting progression. Baseline VEGF and VEGF/sVEGFR-2 values could be useful as early predictors of response. Trial registration ANMAT#4596/09.
format article
artículo
acceptedVersion
author Perroud, Herman A
Alasino, Carlos María 
Rico, María José
Mainetti, Leandro Ernesto
Queralt, Francisco 
Pezzotto, Stella Maris
Rozados, Viviana R.
Scharovsky, O. Graciela
author_facet Perroud, Herman A
Alasino, Carlos María 
Rico, María José
Mainetti, Leandro Ernesto
Queralt, Francisco 
Pezzotto, Stella Maris
Rozados, Viviana R.
Scharovsky, O. Graciela
author_sort Perroud, Herman A
title Metastatic breast cancer patients treated with low-dose metronomic chemotherapy with cyclophosphamide and celecoxib: clinical outcomes and biomarkers of response
title_short Metastatic breast cancer patients treated with low-dose metronomic chemotherapy with cyclophosphamide and celecoxib: clinical outcomes and biomarkers of response
title_full Metastatic breast cancer patients treated with low-dose metronomic chemotherapy with cyclophosphamide and celecoxib: clinical outcomes and biomarkers of response
title_fullStr Metastatic breast cancer patients treated with low-dose metronomic chemotherapy with cyclophosphamide and celecoxib: clinical outcomes and biomarkers of response
title_full_unstemmed Metastatic breast cancer patients treated with low-dose metronomic chemotherapy with cyclophosphamide and celecoxib: clinical outcomes and biomarkers of response
title_sort metastatic breast cancer patients treated with low-dose metronomic chemotherapy with cyclophosphamide and celecoxib: clinical outcomes and biomarkers of response
publisher Springer
publishDate 2018
url http://hdl.handle.net/2133/11096
http://hdl.handle.net/2133/11096
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