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

Autor: Perroud HA; Institute of Experimental Genetics, School of Medical Sciences, National University of Rosario, Santa Fe 3100, S2000KTR, Rosario, Argentina. haperroud@gmail.com.; National Scientific and Technical Research Council (CONICET), Rosario, Argentina. haperroud@gmail.com., Alasino CM; Institute of Oncology of Rosario, Rosario, Argentina., Rico MJ; Institute of Experimental Genetics, School of Medical Sciences, National University of Rosario, Santa Fe 3100, S2000KTR, Rosario, Argentina.; National Scientific and Technical Research Council (CONICET), Rosario, Argentina., Mainetti LE; Institute of Experimental Genetics, School of Medical Sciences, National University of Rosario, Santa Fe 3100, S2000KTR, Rosario, Argentina., Queralt F; Institute of Oncology of Rosario, Rosario, Argentina., Pezzotto SM; Institute of Immunology, School of Medical Sciences, National University of Rosario, Rosario, Argentina.; Research Council of the National University of Rosario (CIUNR), Rosario, Argentina., Rozados VR; Institute of Experimental Genetics, School of Medical Sciences, National University of Rosario, Santa Fe 3100, S2000KTR, Rosario, Argentina., Scharovsky OG; Institute of Experimental Genetics, School of Medical Sciences, National University of Rosario, Santa Fe 3100, S2000KTR, Rosario, Argentina. graciela.scharovsky@gmail.com.; Research Council of the National University of Rosario (CIUNR), Rosario, Argentina. graciela.scharovsky@gmail.com.
Jazyk: angličtina
Zdroj: Cancer chemotherapy and pharmacology [Cancer Chemother Pharmacol] 2016 Feb; Vol. 77 (2), pp. 365-74. Date of Electronic Publication: 2015 Dec 31.
DOI: 10.1007/s00280-015-2947-9
Abstrakt: 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.
Databáze: MEDLINE
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