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.citation.titleCancer Chemotherapy and Pharmacologyes
dc.citation.volume77es
dc.creatorPerroud, Herman A
dc.creatorAlasino, Carlos María 
dc.creatorRico, María José
dc.creatorMainetti, Leandro Ernesto
dc.creatorQueralt, Francisco 
dc.creatorPezzotto, Stella Maris
dc.creatorRozados, Viviana R.
dc.creatorScharovsky, O. Graciela
dc.date.accessioned2018-04-13T15:17:17Z
dc.date.available2018-04-13T15:17:17Z
dc.date.issued2016-02
dc.descriptionBackground 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.filFil: Perroud, Herman A. Institute of Experimental Genetics. School of Medical Sciences. National University of Rosario; Rosario; Argentinaes
dc.description.filFil: Alasino, Carlos María. Institute of Oncology of Rosario; Argentinaes
dc.description.filFil: Rico, María José. Institute of Experimental Genetics. School of Medical Sciences. National University of Rosario; Rosario; Argentinaes
dc.description.filFil: Mainetti, Leandro Ernesto. Institute of Experimental Genetics. School of Medical Sciences. National University of Rosario; Argentinaes
dc.description.filFil: Queralt, Francisco. Institute of Oncology of Rosario; Argentinaes
dc.description.filFil: Pezzotto, Stella Maris. Research Council of the National University of Rosario (CIUNR); Argentinaes
dc.description.filFil: Rozados, Viviana R. Institute of Experimental Genetics. School of Medical Sciences. National University of Rosario; Rosario; Argentinaes
dc.description.filFil: Scharovsky, O. Graciela. Universidad Nacional de Rosario. Consejo de Investigaciones UNR, Facultad de Ciencias Médicas; Argentinaes
dc.description.sponsorshipAgencia 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.formatapplication/pdf
dc.format.extent365–374es
dc.identifier.issn1432-0843es
dc.identifier.urihttp://hdl.handle.net/2133/11096
dc.language.isoenges
dc.publisherSpringeres
dc.relation.publisherversionhttps://doi.org/10.1007/s00280-015-2947-9es
dc.rightsopenAccesses
dc.rights.holderSpringeres
dc.subjectAngiogenesis es
dc.subjectBiomarkers es
dc.subjectCyclophosphamide es
dc.subjectCelecoxib es
dc.subjectMetronomic chemotherapy es
dc.titleMetastatic breast cancer patients treated with low-dose metronomic chemotherapy with cyclophosphamide and celecoxib: clinical outcomes and biomarkers of responsees
dc.typearticle
dc.typeartículo
dc.typeacceptedVersion
dc.type.collectionarticulo
dc.type.versionacceptedVersiones

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