1. Metastatic breast cancer patients treated with low-dose metronomic chemotherapy with cyclophosphamide and celecoxib: clinical outcomes and biomarkers of response.
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Perroud, Herman, Alasino, Carlos, Rico, Maria, Mainetti, Leandro, Queralt, Francisco, Pezzotto, Stella, Rozados, Viviana, Graciela Scharovsky, O., Perroud, Herman Andres, Alasino, Carlos Maria, Rico, Maria Jose, Mainetti, Leandro Ernesto, Pezzotto, Stella Maris, Rozados, Viviana Rosa, and Scharovsky, O Graciela
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METASTATIC breast cancer , *CANCER patients , *CANCER chemotherapy , *CYCLOPHOSPHAMIDE , *CELECOXIB , *THERAPEUTIC use of biochemical markers , *MEDICAL sciences , *TOXICITY testing , *THERAPEUTICS , *ANTINEOPLASTIC agents , *BREAST tumors , *DRUG therapy , *CLINICAL trials , *COMPARATIVE studies , *DRUG monitoring , *DRUG administration , *RESEARCH methodology , *MEDICAL cooperation , *METASTASIS , *RESEARCH , *TUMOR classification , *EVALUATION research , *TREATMENT effectiveness , *DISEASE progression - Abstract
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. [ABSTRACT FROM AUTHOR]- Published
- 2016
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