Auro Del Giglio

Sorafenib in Combination With Capecitabine: An Oral Regimen for Patients With HER2-Negative Locally Advanced or Metastatic Breast Cancer

PURPOSE Sorafenib is a multikinase inhibitor with antiangiogenic/antiproliferative activity. A randomized, double-blind, placebo-controlled phase IIB trial assessed sorafenib with capecitabine for locally advanced or metastatic human epidermal growth factor receptor 2 (HER2) -negative breast cancer. PATIENTS AND METHODS Patients were randomly assigned to first- or second-line capecitabine 1,000 mg/m(2) orally twice a day for days 1 to 14 of every 21-day cycle with sorafenib 400 mg orally twice a day or placebo. The primary end point was progression-free survival (PFS). RESULTS In total, 229 patients were enrolled. The addition of sorafenib to capecitabine resulted in a significant improvement in PFS versus placebo (median, 6.4 v 4.1 months; hazard ratio [HR], 0.58; 95% CI, 0.41 to 0.81; P = .001) with sorafenib favored across subgroups, including first-line (HR, 0.50; 95% CI, 0.30 to 0.82) and second-line (HR, 0.65; 95% CI, 0.41 to 1.04) treatment. There was no significant improvement for overall survival (median, 22.2 v 20.9 months; HR, 0.86; 95% CI, 0.61 to 1.23; P = .42) and overall response (38% v 31%; P = .25). Toxicities (sorafenib v placebo) of any grade included rash (22% v 8%), diarrhea (58% v 30%), mucosal inflammation (33% v 21%), neutropenia (13% v 4%), hypertension (18% v 12%), and hand-foot skin reaction/hand- foot syndrome (HFSR/HFS; 90% v 66%); grade 3 to 4 toxicities were comparable between treatment arms except HFSR/HFS (44% v 14%). Reasons for discontinuation in the sorafenib and placebo arms included disease progression (63% v 82%, respectively), adverse events (20% v 9%, respectively), and death (0% v 1%, respectively). CONCLUSION Addition of sorafenib to capecitabine improved PFS in patients with HER2-negative advanced breast cancer. The dose of sorafenib used in this trial resulted in unacceptable toxicity for many patients. A phase III confirmatory trial has been initiated with a reduced sorafenib dose.

Expression of ck-19, galectin-3 and hbme-1 in the differentiation of thyroid lesions: systematic review and diagnostic meta-analysis

BackgroundTo distinguish between malignant and benign lesions of the thyroid gland histological demonstration is often required since the fine-needle aspiration biopsy method applied pre-operatively has some limitations. In an attempt to improve diagnostic accuracy, markers using immunocytochemistry and immunohistochemistry techniques have been studied, mainly cytokeratin-19 (CK-19), galectin-3 (Gal-3) and Hector Battifora mesothelial-1 (HBME-1). However, current results remain controversial. The aim of the present article was to establish the diagnostic accuracy of CK-19, Gal-3 and HBME-1 markers, as well as their associations, in the differentiation of malignant and benign thyroid lesions.MethodsA systematic review of published articles on MEDLINE and The Cochrane Library was performed. After establishing inclusion and exclusion criteria, 66 articles were selected. The technique of meta-analysis of diagnostic accuracy was employed and global values of sensitivity, specificity, area under the summary ROC curve, and diagnostic odds ratio (dOR) were calculated.ResultsFor the immunohistochemistry technique, the positivity of CK-19 for the diagnosis of malignant thyroid lesions demonstrated global sensitivity of 81% and specificity of 73%; for Gal-3, sensitivity of 82% and specificity of 81%; and for HBME-1, sensitivity of 77% and specificity of 83%. The association of the three markers determined sensitivity of 85%, specificity of 97%, and diagnostic odds ratio of 95.1. Similar results were also found for the immunocytochemistry assay.ConclusionThis meta-analysis demonstrated that the three immunomarkers studied are accurate in pre- and postoperative diagnosis of benign and malignant thyroid lesions. Nevertheless, the search for other molecular markers must continue in order to enhance this diagnostic accuracy since the results found still show a persistency of false-negative and false-positive tests.Virtual slidesHttp://www.diagnosticpathology.diagnomx.eu/vs/3436263067345159

Guarana (Paullinia cupana) Improves Fatigue in Breast Cancer Patients Undergoing Systemic Chemotherapy

BACKGROUND In patients with breast cancer (BC) undergoing systemic chemotherapy, cancer-related fatigue (CRF) is a common problem that can negatively impact quality of life. Guarana (Paullinia cupana) is a plant native to the Amazon basin that has been used as a stimulant since pre-Columbian times. OBJECTIVE The purpose of this study was to evaluate the effectiveness of guarana extract on fatigue, sleep quality, anxiety, depression symptoms, and menopause in a group of BC chemotherapy patients. PATIENTS AND METHODS Patients with progressive fatigue after their first cycle of chemotherapy were randomized to receive either guarana 50 mg by mouth twice daily (32 patients) or placebo (43 patients) for 21 days. After a 7-day washout period, patients were crossed over to the opposite experimental arm. All patients were evaluated on days 1, 21, and 49. The primary endpoint was the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire score, and secondary endpoints were the results of the Functional Assessment of Chronic Illness Therapy-Endocrine Symptoms (FACT-ES), Brief Fatigue Inventory (BFI), Pittsburg Sleep Quality Index, Chalder Fatigue Scale, and Hospital Anxiety and Depression Scale. RESULTS Guarana significantly improved the FACIT-F, FACT-ES, and BFI global scores compared to placebo on days 21 and 49 (p < 0.01). The Chalder Scale improved significantly on day 21 (p < 0.01) but not on day 49 (p = 0.27). Guarana did not produce any Common Terminology Criteria for Adverse Events grades 2, 3, or 4 toxicities and did not worsen sleep quality or cause anxiety or depression. CONCLUSIONS Guarana is an effective, inexpensive, and nontoxic alternative for the short-term treatment of fatigue in BC patients receiving systemic chemotherapy. Further studies are needed to confirm these results and to evaluate their generalizability to chronic CRF and to other types of cancer.

A síndrome da estafa profissional em médicos cancerologistas Brasileiros

OBJETIVOS: A sindrome da estafa profissional (burnout) e um quadro caracterizado por tres dimensoes: exaustao emocional (EE), despersonalizacao (DP) e baixa realizacao pessoal (RP). Na area medica, os cancerologistas estao particularmente predispostos a esta sindrome. O objetivo deste estudo e avaliar sua prevalencia entre cancerologistas brasileiros, correlacionando-a com dados demograficos e caracteristicas de trabalho destes profissionais, avaliando tambem quais as suas sugestoes para prevencao do quadro. METODOS: Tres questionarios foram enviados aos 645 membros da Sociedade Brasileira de Cancerologia, por correio, e, apos dez semanas, foram recebidas 136 respostas. Os questionarios utilizados foram um de opiniao, um geral e o inventario de Maslach de exaustao profissional, que avalia as supramencionadas dimensoes separadamente, caracterizando-as em niveis leve, moderado ou grave. DISCUSSAO: A taxa de resposta obtida foi 21%. A sindrome foi observada em niveis moderados ou graves nas tres dimensoes em 15,7% dos medicos. Para EE, 55,8% apresentaram os niveis moderado ou grave. Para DP, esse numero foi de 96,1% e, para RP, 23,4%. Correlacionando o questionario Maslach com os dados demograficos, encontramos significância estatistica entre pratica de atividade fisica ou hobby e menores niveis de EE (p=0,008) e trabalhar apenas em instituicoes privadas com maiores niveis de DP (p=0,021). Os cancerologistas apontaram como alternativas mais relevantes na prevencao da sindrome menos burocracia (73,5%) e limitacao do numero de pacientes atendidos (72,7%). CONCLUSAO: A sindrome da estafa profissional e frequente entre medicos cancerologistas brasileiros, e outros estudos devem ser desenvolvidos para averiguar sua prevalencia e prevencao em outras especialidades medicas.

Fadiga relacionada ao câncer: uma revisão

A fadiga relacionada ao câncer (FRC) e um dos sintomas mais prevalentes em pacientes com câncer, sendo reportada por 50% a 90% dos pacientes durante o curso da doenca ou do seu tratamento, impactando na qualidade de vida de forma severa alem de diminuir a capacidade funcional diaria dos pacientes. Uma abordagem ampla deve ser realizada com orientacoes gerais sobre fadiga, alem da determinacao de um plano individualizado de abordagem terapeutica. Pacientes com fadiga moderada ou severa devem se beneficiar de ambas as medidas farmacologicas e nao farmacologicas a serem adotadas, enquanto pacientes que apresentem fadiga leve que nao interfira na qualidade de vida podem ser tratados com medidas nao farmacologicas como unica medida terapeutica. O tratamento nao farmacologico se mostra promissor com o uso de terapias cognitivas-comportamentais (conservacao de energia e organizacao de atividades diarias realizadas, ECAM), exercicios fisicos e talvez terapias do sono. O tratamento farmacologico tem mostrado resultados promissores que incluem o uso de psicoestimulantes tais como metilfenidato e dexmetilfenidato, modanafil (em pacientes com fadiga severa) e agentes estimuladores de eritropoietina em pacientes com anemia associada a quimioterapia e hemoglobina menor que 10 mg/dL. Alem dessas drogas, o uso de Guarana (Paullinia cupana) tem-se mostrado uma opcao promissora, com efeitos beneficos no tratamento da fadiga fisica e mental relacionada ao câncer. Por ser uma opcao sem efeitos colaterais significantes e uma planta nacional, torna-se atrativo considerando o facil acesso a esta medicacao por seu baixo custo e facil adesao ao tratamento. O tratamento pode ser oferecido atraves de uma abordagem multimodal e multidisciplinar que individualize as opcoes terapeuticas dentro de um contexto que promova o diagnostico acurado da FRC, alem de um tratamento especifico e adequado para cada paciente que apresente este sintoma tao importante e de grande impacto na qualidade de vida de pacientes com câncer.Cancer-related fatigue is the most prevalent cancer symptom, reported in 50%-90% of patients and severely impacts quality of life and functional capacity. The condition remains underreported and often goes untreated. Guidelines suggest screening for fatigue at the initial visit, when the diagnosis of advanced disease is made, and at each chemotherapy session, as well as the identification of treatable contributing factors such as anemia, hypothyroidism, depression and sleep disorders. Brief assessment tools such as the Brief Fatigue Inventory or the Visual Analog Scale may be appropriate in the initial scoring of fatigue severity, but the initial approach to treatment usually requires a more comprehensive assessment, education, and the determination of an individualized treatment plan. Patients with moderate or severe fatigue may benefit from both pharmacological and non-pharmacological interventions, whereas mild fatigue that does not interfere with quality of life can be treated with non-pharmacological measures alone. Non-pharmacological measures that have shown to be promising include cognitive-behavioral interventions such as energy conservation and activity management (ECAM), exercise and perhaps sleep therapy. Many other modalities may be beneficial and can be used on an individual basis, but there is insufficient evidence to promote any single treatment. Pharmacological therapies that have shown to be promising include the psycho-stimulants methylphenidate and dexmethylphenidate, modafinil (in severely fatigued patients only), and erythropoietin-stimulating agents in patients with chemotherapy-associated anemia and hemoglobin levels < 10 g/dL. Recently, our group reported impressive results with the use of the dry extract of Guarana (Paullinia cupana), with no significant side effects and at low cost, for the treatment of physical and mental cancer-related fatigue.

Ratio between positive lymph nodes and total dissected axillaries lymph nodes as an independent prognostic factor for disease-free survival in patients with breast cancer

The number of positive axillary lymph nodes involved by tumor is one of the main prognostic factors for women with locoregional breast cancer (BC) for whom adjuvant chemotherapy is being considered. The prognostic importance of the ratio (P/D) between positive lymph nodes (P) and total dissected lymph nodes (D), previously demonstrated in the high-dose chemotherapy (HDC) setting has not yet been tested, however, in the conventional adjuvant chemotherapy setting. The data of 168 patients who were from 2 institutions and who were treated with adjuvant chemotherapy for BC were retrospectively analyzed, and univariate and multivariate analysis were performed, including the other traditional prognostic factors and P/D ratio as possible predictors of disease free survival (DFS). Disease-free survival for quartile 4 of P/D ratio (ratio >0.30) was statistically different from that for the other quartiles (log-rank test p < 0.001). Mean DFS for this series was not reached as well as for quartiles 1, 2, and 3, while mean DFS for quartile 4 was 44.5 months. In univariate analysis, number of positive lymph nodes (r2 = 0.055; p = 0.023), P/D ratio (r2 = 0.213; p < 0.001), and stage (r2 = 0.105; p = 0.002) were predictive of relapse, while in multivariate analysis, only P/D ratio remained an independent predictor of relapse (r2 = 0.213; p < 0.001). It is concluded that P/D ratio could become a simple, inexpensive, and easily available prognostic factor for patients undergoing conventional chemotherapy for BC.

Bisphosphonate therapy in patients under androgen deprivation therapy for prostate cancer: a systematic review and meta-analysis

The objective of this study was to clarify the role of bisphosphonates in the treatment of osteoporosis in patients with prostate adenocarcinoma under androgen deprivation therapy (ADT). The Medline, EMBASE, Cancerlit and the American Society of Clinical Oncology abstract databases were searched for published randomized, placebo-controlled trials evaluating the usage of bisphosphonates in patients with prostate cancer (PC) under ADT. The outcomes assessed were fracture, osteoporosis, incidence of adverse events and changes in bone mineral density (BMD) during treatment. A total of 15 articles (2634 participants) were included in the meta-analysis. Treatment with bisphosphonates showed a substantial effect in preventing fractures (risk ratio (RR), 0.80; P=0.005) and osteoporosis (RR, 0.39; P <0.00001). Zoledronic acid showed the best number needed to treat (NTT), compared with placebo, in relation to fractures and osteoporosis (NNT=14.9 and NNT=2.68, respectively). The between-group difference (bisphosphonates vs placebo) in the lumbar spine and femoral neck BMD were 5.18±3.38% and 2.35±1.16%, respectively. This benefit of bone loss prevention could be reached without major side effects (cardiovascular or gastrointestinal events). Bisphosphonates are effective in preventing bone loss in patients with PC who are under ADT.

Análise do atraso no diagnóstico e tratamento do câncer de mama em um hospital público

BACKGROUND: To identify potential delays in the management of patients with breast cancer examined at a public hospital, from time of suspicion until diagnosis and beginning of treatment. METHODS: Retrospective study which analyzed data related to time elapsed in different intervals between suspicion, diagnosis and onset of systemic cancer-directed treatments, of consecutive breast cancer patients cared for at the medical oncology clinic of the Mario Covas Hospital during 2006. RESULTS: Sixty-eight women, with a mean age of 56.3 years (standard deviation: 12.2 years), were included. Of all the intervals, the longest delay occurred between the mammographic suspicion of cancer and performance of biopsy (median of 72 days, range: 4 - 1095 days); this was significantly longer (P<0.001) than in the other intervals analyzed. Furthermore, this interval in particular, was significantly longer in patients with advanced stage breast cancer when compared to those at the initial stage (P=0.014). CONCLUSION: Breast cancer patients treated in a public hospital in Brazil suffer delays, especially during the diagnosis of their disease. Minimizing the time between mammography and biopsy of suspicious lesions appears to be the most crintical step to correct this situation.

Effectiveness of guaraná (Paullinia cupana) for postradiation fatigue and depression: Results of a pilot double-blind randomized study

CONTEXT AND OBJECTIVE Guaraná (Paullinia cupana) has been used medicinally for centuries. The aim of this study is evaluate the effectiveness of guaraná in the treatment of postradiation depression and fatigue. DESIGN AND SETTING This study had a double-blind randomized design with crossover between experimental arms, at Faculdade de Medicina da Fundação do ABC. METHODS We conducted a randomized double-blind crossover trial with 36 patients with breast cancer undergoing adjuvant radiation therapy. We randomized patients to either guaraná 75 mg daily p.o. or to placebo. Patients were switched to the other experimental arm at the middle of the radiation treatment, which consisted of 28 daily fractions of 180 cGy. Evaluations were conducted at the beginning, at the middle, and at the end of radiation therapy. RESULTS We were unable to show any statistically significant differences between the guaraná and the placebo-treated group with any of the measured scores. Also, within the same group, we did not see any statistically significant associations during either the guaraná- or placebo-treated periods with any of the aforementioned measures. CONCLUSIONS We were unable to show that patients with breast cancer undergoing radiation therapy derive any advantage with guaraná over placebo for both fatigue and depressive symptoms.

Use of unnecessary medications by patients with advanced cancer: cross-sectional survey

BackgroundCancer patients at the end of life take numerous medications. However, it has not been assessed what proportion of patients take unnecessary medications and which patients are at risk for doing so.MethodsCross-sectional survey of medications utilized by terminally ill ambulatory cancer patients, with the aim of identifying medications considered unnecessary as per explicit criteria. The criteria took into account whether drugs could benefit patients with terminal cancer.ResultsAmong 87 patients, 21 (24%, 95% confidence interval [CI] 15.6–34.5%) were taking at least one unnecessary medication, the most common being gastric protectors. In multivariable analyses, patients with Charlson Comobidity Index ≤ 1 (OR: 4.49, CI95% 1.32–15.26; p = 0.01) or whose medication list had not been reconciled by physicians (OR: 6.38, CI95% 1.21–33.40; p = 0.02) were more likely to use an unnecessary medication.ConclusionPatients with advanced cancer take many medications considered unnecessary. Medication reconciliation should be performed routinely for these patients.