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

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dc.creator Perroud, Herman A
dc.creator Alasino, Carlos María 
dc.creator Rico, María José
dc.creator Mainetti, Leandro Ernesto
dc.creator Queralt, Francisco 
dc.creator Pezzotto, Stella Maris
dc.creator Rozados, Viviana R.
dc.creator Scharovsky, O. Graciela
dc.date.accessioned 2018-04-13T15:17:17Z
dc.date.available 2018-04-13T15:17:17Z
dc.date.issued 2016-02
dc.identifier.issn 1432-0843 es
dc.identifier.uri http://hdl.handle.net/2133/11096
dc.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. es
dc.description.sponsorship Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT) [Grant Number: PICT 2006/1908 to OGS, VRR, SMP and CMA]. The National Cancer Institute at the National Institutes of Health grants for doctoral fellows to HAP. HAP is a fellow of Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET). es
dc.format application/pdf
dc.format.extent 365–374 es
dc.language.iso eng es
dc.publisher Springer es
dc.rights openAccess es
dc.subject Angiogenesis  es
dc.subject Biomarkers  es
dc.subject Cyclophosphamide  es
dc.subject Celecoxib  es
dc.subject Metronomic chemotherapy  es
dc.title Metastatic breast cancer patients treated with low-dose metronomic chemotherapy with cyclophosphamide and celecoxib: clinical outcomes and biomarkers of response es
dc.type article
dc.type artículo
dc.type acceptedVersion
dc.rights.holder Springer es
dc.relation.publisherversion https://doi.org/10.1007/s00280-015-2947-9 es
dc.citation.title Cancer Chemotherapy and Pharmacology es
dc.citation.volume 77 es
dc.description.fil Fil: Perroud, Herman A. Institute of Experimental Genetics. School of Medical Sciences. National University of Rosario; Rosario; Argentina es
dc.description.fil Fil: Alasino, Carlos María. Institute of Oncology of Rosario; Argentina es
dc.description.fil Fil: Rico, María José. Institute of Experimental Genetics. School of Medical Sciences. National University of Rosario; Rosario; Argentina es
dc.description.fil Fil: Mainetti, Leandro Ernesto. Institute of Experimental Genetics. School of Medical Sciences. National University of Rosario; Argentina es
dc.description.fil Fil: Queralt, Francisco. Institute of Oncology of Rosario; Argentina es
dc.description.fil Fil: Pezzotto, Stella Maris. Research Council of the National University of Rosario (CIUNR); Argentina es
dc.description.fil Fil: Rozados, Viviana R. Institute of Experimental Genetics. School of Medical Sciences. National University of Rosario; Rosario; Argentina es
dc.description.fil Fil: Scharovsky, O. Graciela. Universidad Nacional de Rosario. Consejo de Investigaciones UNR, Facultad de Ciencias Médicas; Argentina es
dc.type.collection articulo
dc.type.version acceptedVersion es


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