Artículo
Metastatic breast cancer patients treated with low-dose metronomic chemotherapy with cyclophosphamide and celecoxib: clinical outcomes and biomarkers of response
Perroud, Herman Andrés
; Alasino, Carlos Maria; Rico, Maria Jose
; Mainetti, Leandro Ernesto
; Queralt, Francisco; Pezzotto, Stella Maris; Rozados, Viviana Rosa
; Scharovsky, Olga Graciela
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Fecha de publicación:
02/2016
Editorial:
Springer
Revista:
Cancer Chemotherapy And Pharmacology
ISSN:
0344-5704
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
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.
Palabras clave:
ANGIOGENESIS
,
BIOMARKERS
,
CELECOXIB
,
CYCLOPHOSPHAMIDE
,
METRONOMIC CHEMOTHERAPY
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Licencia
Identificadores
Colecciones
Articulos(CCT - ROSARIO)
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - ROSARIO
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - ROSARIO
Citación
Perroud, Herman Andrés; Alasino, Carlos Maria; Rico, Maria Jose; Mainetti, Leandro Ernesto; Queralt, Francisco; et al.; Metastatic breast cancer patients treated with low-dose metronomic chemotherapy with cyclophosphamide and celecoxib: clinical outcomes and biomarkers of response; Springer; Cancer Chemotherapy And Pharmacology; 77; 2; 2-2016; 365-374
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