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It is well known that low-dose metronomic chemotherapy has antiangiogenicactivity. The aim of the present trial was to investigate the antiangiogenic propertiesof weekly docetaxel in patients with metastatic breast cancer. In total, 157 metastaticbreast cancer patients received 35 mg/m2 docetaxel weekly as a recommended treatment.Blood samples were collected before the start of chemotherapy (baseline) and duringtreatment. Nitric oxide (NO) and vascular endothelial growth factor A (VEGF-A)plasma levels were measured at baseline and during treatment, while VEGF-A, endothelialnitric oxide synthase (eNOS) and thrombospondin-1 (THBS-1) peripheral blood mRNAlevels were measured at baseline, in 127 patients and 39 female healthy controls.In general, the treatment was well-tolerated. Sixty-one patients (38%) achievedan objective response (4% complete and 34% partial response), while 52 (33%) hadstable disease and 27 (17%) progressed. At a median follow-up of 33.5 months (range2.8-45.0), 118 patients (74%) demonstrated disease progression and 94 (59%) haddied. Median progression-free survival (PFS) was 8.8 months and median overallsurvival (OS) was 27.7 months. Median baseline level of plasma NO was significantlylower in patients than in healthy controls (p=0.010), while none of the plasmamarkers significantly changed upon docetaxel treatment. In addition, the medianrelative quantification value for THBS-1 mRNA was significantly higher (p&lt;0.001)in patients as compared to healthy controls. NO plasma levels were positivelyassociated with the number of organs involved (p=0.008). In multivariate analysis,low eNOS mRNA levels showed adverse prognostic significance for OS and high THBS-1mRNA levels were found to be associated with shorter OS and PFS, independentlyfrom established clinical prognostic factors. Although an antiangiogenic activityof weekly docetaxel was not demonstrated in the present study, some interestingobservations regarding the prognostic role of a number of blood angiogenic markerscould be made.

oncology reports

Expression of angiogenic markers in the peripheral blood of docetaxel-treated advanced breast cancer patients: A Hellenic Cooperative Oncology Group (HeCOG) study