Complete blood sample including serum hematology and biochemistry was collected every 4 weeks; serum hematology was performed also at each cycle (every 14 days)
Complete blood sample including serum hematology and biochemistry was collected every 4 weeks; serum hematology was performed also at each cycle (every 14 days). All individuals had remaining ventricular ejection portion (LVEF) measurement of at least 50% by echocardiography or MUGA check out. The term metronomic chemotherapy (MTC) refers to the frequent, actually daily administration of chemotherapeutics at doses significantly below the maximum tolerated dose, with no long term drug-free breaks [10]. It also defines a novel target of antitumor therapies. Preclinical studies possess recognized the tumor endothelial cell as the main target of MTC, but others mechanisms of action operating in MTC, such as stimulation of immune response, circulating endothelial cells (CECs) inhibition and direct action on tumor cells have been described too [11]. Inside a earlier small series, low-dose oral cyclophosphamide and methotrexate combined with trastuzumab have shown substantial effectiveness in metastatic HER-2 positive breast cancer and offered disease control in Mouse monoclonal to CD4.CD4, also known as T4, is a 55 kD single chain transmembrane glycoprotein and belongs to immunoglobulin superfamily. CD4 is found on most thymocytes, a subset of T cells and at low level on monocytes/macrophages a significant proportion of individuals. The observed medical benefit (RP plus RC plus SD for??24 weeks) in all individuals and in individuals with disease resistant to earlier trastuzumab therapy was 46% (95% CI, 24C68%) and 27% (95% CI, 6C61%), respectively [12]. Data from a phase II trial with the combination of metronomic capecitabine plus cyclophosphamide routine plus bevacizumab (a humanized monoclonal antibody against vascular endothelial growth factor, VEGF) have shown a high medical benefit rate in untreated breast cancer individuals [13]. In the present study we assessed the activity and tolerability of a new metronomic routine with cyclophosphamide plus capecitabine in combination with trastuzumab in HER-2 positive untreated metastatic breast malignancy individuals. 2.?Patients and methods Metoclopramide 2.1. Study design This phase II study was designed relating to an ideal two-stage design to test the null hypothesis that p0 0.4 vs. the alternative that p1 0.6 with ?=?0.05 e ?=?0.1 [14]. According to the initial design, after screening the routine on 25 individuals in the 1st stage, the trial would have been terminated if 11 or fewer reactions were recorded. Conversely, the continuation to the second stage implied to enroll a total of 66 individuals. According to the study design, study routine should be considered active if the total quantity responding is higher than 32 out of 66 evaluable individuals.gene copy quantity/CEP17 signals 2 by FISH). IHC for ER (Estrogen receptor) and PgR (Progesteron receptor) was defined positive if??1% immune-stained tumor cells were detected. 2.4. Treatment routine Individuals received Trastuzumab in the dose of 4?mg/kg by intravenous infusion every 14 days (loading dose at first administration 6?mg/kg), dental cyclophosphamide 50?mg daily and oral capecitabine 500? mg three times each day continually. Every cycle started with each administration of Trastuzumab. Endocrine therapy for endocrine-responsive disease was not admitted during study treatment. 2.5. Assessment The response and progression were evaluated using the international criteria proposed from the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Individuals were Metoclopramide tested for response every 8 weeks (every 4 weeks for superficial lesions) by CT scan or MRI. In addition, confirmatory scans should also be obtained not more than 4 weeks following initial paperwork of objective response. Adverse events were evaluated according to the Common Terminology Criteria for Adverse Effects Version 4.0 (CTCAE 4.0). Total blood sample including serum hematology and biochemistry was collected every 4 weeks; serum hematology was performed also at each cycle (every 14 days). All individuals had remaining ventricular ejection portion (LVEF) measurement of Metoclopramide at least 50% by echocardiography or MUGA scan. Subsequent scheduled LVEF assessments were performed every 3 months during treatment and every 6 months during follow-up. 3.?Results From November 2011 to September 2015, 60 individuals were enrolled. The median age was 62.5 years (range 32C87). Median DFI (disease-free interval) was 41 weeks (range 5C252). Main individuals features are summarized in Table?1. Seventeen individuals.