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Brescia, Italy

Bazzola L.,Uodi Patologia Mammaria Breast Cancer Unit | Foroni C.,Uodi Patologia Mammaria Breast Cancer Unit | Andreis D.,Uodi Patologia Mammaria Breast Cancer Unit | Zanoni V.,Uodi Patologia Mammaria Breast Cancer Unit | And 19 more authors.
British Journal of Cancer | Year: 2015

Purpose: To assess whether the combination of letrozole, metronomic cyclophosphamide and sorafenib (LCS) is well tolerated and shows activity in primary breast cancer (BC). Methods: Thirteen oestrogen receptor-positive, postmenopausal, T2-4, N0-1 BC patients received the LCS combination for 6 months. In these patients we examined the pharmacokinetics of sorafenib and cyclophosphamide, toxicity of the regimen, the clinical response to therapy and changes in the levels of biologically relevant biomarkers. Results: Adequate plasma concentrations of sorafenib were achieved in patients when it was dosed in combination with L+C. The mean plasma concentrations of C were consistently lower following administration of LCS, compared with administration of L+C only. The most common drug-related grade 3/4 adverse events were skin rash (69.3%), hand-foot skin reaction (69.3%) and diarrhoea (46.1%). According to RECIST Criteria, a clinical complete response was observed in 6 of 13 patients. A significant reduction in tumour size, evaluated with MRI, was also observed between baseline and 14 days of treatment in all 13 patients (P=0.005). A significant reduction in SUV uptake, measured by 18FDG-PET/CT, was observed in all patients between baseline and 30 days of treatment (P=0.015) and between baseline and definitive surgery (P=0.0002). Using modified CT Criteria, a response was demonstrated in 8 out of 10 evaluable patients at 30 days and in 11 out of 13 evaluable patients at the definitive surgery. A significant reduction in Ki67 expression was observed in all patients at day 14 compared with baseline (P<0.00001) and in 9 out of 13 patients at the definitive surgery compared with baseline (P<0.03). There was also a significant suppression of CD31 and VEGF-A expression in response to treatment (P=0.01 and P=0.007, respectively). Conclusions: The LCS combination is feasible and tolerable. The tumour response and target biomarker modulation indicate that the combination is clinically and biologically active. © 2015 Cancer Research UK. Source

Consoli F.,Beretta Foundation | Arcangeli G.,Beretta Foundation | Ferrari V.,Beretta Foundation | Grisanti S.,Beretta Foundation | And 3 more authors.
Case Reports in Oncology | Year: 2011

We report the case of a 67-year-old man affected by metastatic esophageal cancer. The patient developed a symptomatic heart metastasis presenting as mimicking ST-segment elevation myocardial infarction. Cardiac magnetic resonance imaging (MRI) documented the presence of a mass in the apex and septum of the left ventriculum. The dissemination of cancer was confirmed by the detection of circulating tumor cells (CTCs) in the peripheral blood, measured by the CellSearch System (Veridex, LLC, Raritan, N.J., USA). The blood sample drawn at cardiac disease progression revealed the presence of 2 CTCs per 7.5 ml of blood. This report highlights the potential role of CTCs as markers of metastatic spread. Copyright © 2011 S. Karger AG, Basel. Source

Consoli F.,Medical Oncology Unit | Grisanti S.,Medical Oncology Unit | Amoroso V.,Medical Oncology Unit | Almici C.,Azienda Spedali Civili | And 3 more authors.
Tumori | Year: 2011

Aims and background. Circulating tumor cells have a prognostic role in metastatic breast cancer. The aim of the study was to confirm the ability of circulating tumor cells, detected by the US Food and Drug Administration approved Cell Search assay, to predict the outcome of patients treated in a community general hospital. Patients and methods. A prospective mono-institutional study was conducted at the Department of Medical Oncology at Spedali Civili, Brescia, Italy, from January 2009 to September 2010. A total of 93 consecutive patients with metastatic breast cancer were enrolled. Patients underwent a blood sample collection to detect circulating tumor cells at baseline and, subsequently, at the first follow-up examination (after 3-4 weeks from the beginning of a systemic therapy). A third sample was drawn at disease progression (at the beginning of a subsequent new course of therapy). The prognostic cutoff value of circulating tumor cells was fixed at 5 cells/7.5 ml of blood. Results. At baseline, median overall survival and progression-free survival in the subgroup &γε;5 circulating tumor cells/7.5 ml of blood were significantly shorter (5 months and 3 months, respectively) than in the subgroup with <5 circulating tumor cells (8 months and 7 months, respectively) (P = 0.003 and P <0.001). At the first follow-up, the subgroup with more than 5 circulating tumor cells/7.5 ml of blood had a median overall survival of 4 months versus 8 months in the subgroup with <5 circulating tumor cells (P <0.001) and a median progression-free survival of 3 months versus 7 months respectively (P <0.001). At multivariate analysis, the level of circulating tumor cells at the first follow-up and at baseline remained significant as a predictor of progression- free and overall survival. The number of metastatic sites was significantly associated with overall and progression-free survival and correlated with the number of circulating tumor cells. Conclusions. Our study confirms the role of circulating tumor cells as predictors of prognosis in metastatic breast cancer patients treated in general clinical practice. Source

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