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Araujo J.C.,University of Houston | Trudel G.C.,Bristol Myers Squibb | Saad F.,Center Hospitalier Of Luniversite Of Montreal | Armstrong A.J.,Duke University | And 22 more authors.
The Lancet Oncology | Year: 2013

Background: Src kinase-mediated interactions between prostate cancer cells and osteoclasts might promote bone metastasis. Dasatinib inhibits tyrosine kinases, including Src kinases. Data suggests that dasatinib kinase inhibition leads to antitumour activity, affects osteoclasts, and has synergy with docetaxel, a first-line chemotherapy for metastatic castration-resistant prostate cancer. We assessed whether dasatinib plus docetaxel in chemotherapy-naive men with metastatic castration-resistant prostate cancer led to greater efficacy than with docetaxel alone. Methods: In this double-blind, randomised, placebo-controlled phase 3 study, we enrolled men of 18 years or older with chemotherapy-naive, metastatic, castration-resistant prostate cancer, and adequate organ function from 186 centres across 25 countries. Eligible patients were randomly assigned (1:1) via an interactive voice response system to receive docetaxel (75 mg/m2 intravenously every 3 weeks, plus oral prednisone 5 mg twice daily), plus either dasatinib (100 mg orally once daily) or placebo until disease progression or unacceptable toxicity. Randomisation was stratified by Eastern Cooperative Oncology Group performance status (0-1 vs 2), bisphosphonate use (yes vs no), and urinary N-telopeptide (uNTx) value (<60 μmol/mol creatinine vs ≥60 μmol/mol creatinine). All patients, investigators, and personnel involved in study conduct and data analyses were blinded to treatment allocation. The primary endpoint was overall survival, analysed by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00744497. Findings: Between Oct 30, 2008, and April 11, 2011, 1522 eligible patients were randomly assigned to treatment; 762 patients were assigned to dasatinib and 760 to placebo. At final analysis, median follow-up was 19·0 months (IQR 11·2-25·1) and 914 patients had died. Median overall survival was 21·5 months (95% CI 20·3-22·8) in the dasatinib group and 21·2 months (20·0-23·4) in the placebo group (stratified hazard ratio [HR] 0·99, 95·5% CI 0·87-1·13; p=0·90). The most common grade 3-4 adverse events included diarrhoea (58 [8%] patients in the dasatinib group vs 27 [4%] patients in the placebo group), fatigue (62 [8%] vs 42 [6%]), and asthenia (40 [5%] vs 23 [3%]); grade 3-4 pleural effusions were uncommon (ten [1%] vs three [<1%]). Interpretation: The addition of dasatinib to docetaxel did not improve overall survival for chemotherapy-naive men with metastatic castration-resistant prostate cancer. This study does not support the combination of dasatinib and docetaxel in this population of patients. Funding: Bristol-Myers Squibb. © 2013 Elsevier Ltd.

Costa M.M.,Hospital do Cancer de Barretos | Silva S.B.,Sapucai Valley University | Quinto A.L.P.,Hospital do Cancer de Barretos | Pasquinelli P.F.S.,Oncominas | And 4 more authors.
Trials | Year: 2014

Background: Breast neoplasms are the second most common type of cancer worldwide, and radiation therapy is a key component of their treatment. Acute skin reactions are one of the most common side effects of radiation therapy, and prevention of this adverse event has been investigated in several studies. However, a clinically applicable, preventative treatment remains unavailable. It has been demonstrated that application of a low-power laser can promote tissue repair. Therefore, the aim of this trial is to evaluate the effectiveness of an indium gallium aluminum phosphorus (InGaAIP) laser operated at 660nm in preventing radiodermatitis in women undergoing adjuvant radiotherapy for breast cancer. Methods/Design: This is a two-arm, randomized controlled trial. A total of 52 patients undergoing radiotherapy for breast cancer (stages I to III) will be enrolled. Patients will be randomly assigned to an intervention group to receive laser therapy (n=26) or a control group to receive a placebo (n=26). The laser or placebo will be applied five days a week, immediately before each radiotherapy session. Skin reactions will then be graded weekly by a nurse, a radiotherapist, and an oncologist (all of whom will be blinded) using the Common Toxicity Criteria (CTC) developed by the National Cancer Institute and the Acute Radiation Morbidity Scoring Criteria developed by the Radiation Therapy Oncology Group. Patients will also answer a modified visual analogue scale for pain (a self-evaluation questionnaire). Primary and secondary outcomes will be the prevention of radiodermatitis and pain secondary to radiodermatitis, respectively. Discussion: The ideal tool for preventing radiodermatitis is an agent that mediates DNA repair or promotes cell proliferation. Application of a low-power laser has been shown to promote tissue repair by reducing inflammation and inducing collagen synthesis. Moreover, this treatment approach has not been associated with adverse events and is cost-effective. Thus, the results of this ongoing trial may establish whether use of a low-power laser represents an ideal treatment option for the prevention of radiodermatitis. © 2014 Costa et al.

Silva Jr J.M.,Hospital do Servidor Publico Estadual SP | Silva Jr J.M.,University of Sao Paulo | De Oliveira A.M.R.R.,Hospital das Clinicas SP FMUSP | Nogueira F.A.M.,Hospital do Servidor Publico Estadual SP | And 8 more authors.
Critical Care | Year: 2013

Introduction: In some studies including small populations of patients undergoing specific surgery, an intraoperative liberal infusion of fluids was associated with increasing morbidity when compared to restrictive strategies. Therefore, to evaluate the role of excessive fluid infusion in a general population with high-risk surgery is very important. The aim of this study was to evaluate the impact of intraoperative fluid balance on the postoperative organ dysfunction, infection and mortality rate.Methods: We conducted a prospective cohort study during one year in four ICUs from three tertiary hospitals, which included patients aged 18 years or more who required postoperative ICU after undergoing major surgery. Patients who underwent palliative surgery and whose fluid balance could change in outcome were excluded. The calculation of fluid balance was based on preoperative fasting, insensible losses from surgeries and urine output minus fluid replacement intraoperatively.Results: The study included 479 patients. Mean age was 61.2 ± 17.0 years and 8.8% of patients died at the hospital during the study. The median duration of surgery was 4.0 (3.2 to 5.5) h and the value of the Simplified Acute Physiology Score (SAPS) 3 score was 41.8 ± 14.5. Comparing survivors and non-survivors, the intraoperative fluid balance from non-survivors was higher (1,950 (1,400 to 3,400) mL vs. 1,400 (1,000 to 1,600) mL, P <0.001). Patients with fluid balance above 2,000 mL intraoperatively had a longer ICU stay (4.0 (3.0 to 8.0) vs. 3.0 (2.0 to 6.0), P <0.001) and higher incidence of infectious (41.9% vs. 25.9%, P = 0.001), neurological (46.2% vs. 13.2%, P <0.001), cardiovascular (63.2% vs. 39.6%, P <0.001) and respiratory complications (34.3% vs. 11.6%, P <0.001). In multivariate analysis, the fluid balance was an independent factor for death (OR per 100 mL = 1.024; P = 0.006; 95% CI 1.007 to 1.041).Conclusions: Patients with excessive intraoperative fluid balance have more ICU complications and higher hospital mortality. © 2013 Silva et al.; licensee BioMed Central Ltd.

Kaminagakura E.,A.C. Camargo Hospital | Vartanian J.G.,A.C. Camargo Hospital | Da Silva S.D.,A.C. Camargo Hospital | Dos Santos C.R.,Hospital do Cancer de Barretos | Kowalski L.P.,A.C. Camargo Hospital
Head and Neck | Year: 2010

Background. Oral squamous cell carcinoma affects mainly patients between the fifth and sixth decades of life, being rare in the young (≤40 years old). Methods. Demographic, clinical, and pathologic features, and the long-term survival of 125 patients younger than 41 years of age were compared with 250 control patients older than 50 years old. Data were submitted to Kaplan-Meier and log-rank tests. Results. The percentage of nonsmokers was higher in the younger patients (p =.04). In the younger patients, tumors at advanced clinical stage (p <01) and poorly differentiated tumors (p =.01) were associated with a higher risk of recurrence. The relapse rate was higher in the younger patients (p =.02); however, there was no significant difference on overall survival (p =.86). The younger patients diagnosed after the 1990s had less advanced clinical stage tumors, had an increase in the use of combination of surgery, radiotherapy, and chemotherapy, and their overall survival was improved. Conclusion. This study emphasizes the importance of early diagnosis and aggressive treatment of oral squamous cell carcinoma. © 2010 Wiley Periodicals, Inc.

Begnami M.D.,Hospital AC Camargo | Fregnani J.H.T.G.,Hospital do Cancer de Barretos | Nonogaki S.,Hospital AC Camargo | Nonogaki S.,Institute Adolpho Lutz | Soares F.A.,Hospital AC Camargo
Human Pathology | Year: 2010

The cell cycle progression is regulated by interactions of specific cyclin-dependent kinases at the G1-S and G2-M checkpoints. In addition, the cell cycle dysregulation plays a major role in carcinogenesis of human cancers. To investigate the role of cell cycle regulators in the pathogenesis and progression of human gastric cancer, the expression of cyclin D1, A, B1, p16INK4a, p21CPI1, p27KIP1, p53, and pRb was investigated in 482 gastric carcinomas using immunohistochemistry in terms of histologic type, tumor invasion, size, location, and metastatic behavior. The cyclin D1, A, and B1 expression (>10%) was observed in 49%, 69%, and 49% of the cases, respectively. Negative cases for p16INK4a, p21 CPI1, and p27KIP1 were detected in 90%, 86%, and 50.5%. There were 30% and 68% of the gastric tumors positive for p53 and pRb, respectively. Diffuse carcinomas frequently were positive for cyclin B1 and pRb, and negative for p21. A relationship between p53 expression and intestinal type carcinomas was found. In addition, the expression of cyclin B1 was associated with regional lymph node metastasis and poor prognosis. No relationship was noticed between any other cell cycle proteins expression and age, sex, tumor size, tumor location, and lymph node involvement. These findings have shown alterations in several cell cycle regulators, and it was suggested that cyclin B1 expression is closely associated with poor behavior in gastric cancer. © 2010 Elsevier Inc.

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