A Phase II Randomized Study of Lapatinib Combined With Capecitabine, Vinorelbine, or Gemcitabine in Patients With HER2-Positive Metastatic Breast Cancer With Progression After a Taxane (Latin American Cooperative Oncology Group 0801 Study).

BACKGROUND: Novel targeted agents and combinations have become available in multiple lines of treatment for human epidermal growth factor receptor 2-positive (HER2(+)) metastatic breast cancer (MBC). In this context, alternatives to the lapatinib (L) and capecitabine (C) regimen, evaluating L combined with other cytotoxic drugs, are warranted. PATIENTS AND METHODS: In the present phase II, multicenter study, patients with HER2(+) MBC with progression after taxane were randomized between L, 1250 mg, combined with C, 2000 mg/m(2) on days 1 to 14 (LC), vinorelbine (V), 25 mg/m(2) on days 1 and 8 (LV), or gemcitabine (G), 1000 mg/m(2) on days 1 and 8 (LG), every 21 days. The primary endpoint was the overall response rate. RESULTS: A total of 142 patients were included from 2009 to 2012. No differences were found in the patient baseline characteristics. The median age was 51 years, 69% were postmenopausal, 32% had liver metastasis, 57% were hormone receptor negative, and 48% had been previously treated with trastuzumab. The overall response rate was 49% (95% confidence interval [CI], 34.8%-63.4%), 56% (95% CI, 40%-70.4%), and 41% (95% CI, 27%-56.8%) in the LC, LV, and LG groups, respectively. The median progression-free survival was 9 months in the LC arm and 7 months in the other 2 arms (P = .28). The most common grade 3 and 4 adverse events were hand-foot syndrome (18%), diarrhea (6%), and increased alanine aminotransferase/aspartate aminotransferase (4%) in the LC arm; neutropenia (36%), diarrhea (9%), and febrile neutropenia (6%) in the LV arm; and neutropenia (47%), alanine aminotransferase/aspartate aminotransferase (13%), and rash (4%) in the LG arm. CONCLUSION: LV and LG seem to be active combinations in patients with HER2(+) MBC after taxane failure. The overall toxicity was manageable in all regimens.

Bupropion for control of hot flashes in breast cancer survivors: a prospective, double-blind, randomized, crossover, pilot phase II trial.

CONTEXT: Hot flashes (HFs) and sexual dysfunction often affect breast cancer (BC) survivors and compromise their quality of life. Bupropion is an antidepressive medication used for smoking cessation and also has been previously studied for the treatment of sexual dysfunction. OBJECTIVES: We aimed to evaluate bupropion's efficacy in controlling HFs in BC survivors. METHODS: This was a randomized, double-blind, crossover, placebo-controlled pilot study that enrolled 55 BC survivors who reported more than seven HFs per week. Subjects were randomized to receive either bupropion 150mg twice daily for four weeks followed by one week of washout and four more weeks of placebo twice daily or vice versa. The primary end point was average daily HF activity (number of HFs and a score combining number and severity) reported while on bupropion or on placebo. Secondary end points were sexual dysfunction, depression, and quality of life evaluated with the Arizona Sexual Experience Scale, Beck Depression Inventory, and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30, respectively. RESULTS: Bupropion reduced HFs by 1.26 per day and the HF score by 6.31%, whereas placebo reduced HFs by 2.11 per day (P>0.05) and the HF score by 30.47% (P>0.05). There were no statistically significant differences between bupropion and placebo in the Arizona Sexual Experience Scale, Beck Depression Inventory, and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30. At the end of the study, 47% of the patients preferred bupropion, whereas 53% preferred placebo. There were no statistically significant differences in side effects between the study groups. CONCLUSION: Compared with placebo, bupropion did not control HFs in this group of BC survivors.

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.

Gabapentin for the prevention of chemotherapy- induced nausea and vomiting: a pilot study.

INTRODUCTION: Chemotherapy-induced nausea and vomiting (CINV) is a distressing side effect that affects many patients undergoing emetogenic chemotherapy, despite the use of antiemetic medications. The purpose of this trial was to evaluate the efficacy and safety of gabapentin for the prevention of CINV during the first cycle of treatment in patients receiving moderately or highly emetogenic chemotherapy. METHODS: Eighty chemotherapy-naive patients, scheduled to receive moderately and highly emetogenic chemotherapy, were enrolled in this randomised, double-blind, placebo-controlled clinical trial. All patients received intravenous ondansetron 8 mg, dexamethasone 10 mg and ranitidine 50 mg before chemotherapy on day 1 and oral dexamethasone 4 mg twice a day on days 2 and 3. Patients were randomly assigned to take gabapentin 300 mg or placebo on the following schedule: 5 and 4 days before chemotherapy once daily, 3 and 2 days before chemotherapy twice daily, 1 day before to 5 days after chemotherapy thrice daily. The primary endpoint was complete overall protection from both vomiting and nausea over the course of the entire study (day 1 through day 5), and complete protection during the delayed period (24-120 h after chemotherapy). RESULTS: The proportion of patients achieving complete response improved from 40% to 62.5%, (p = 0.04) when comparing the control group and the gabapentin group, respectively. In the subset of patients who achieved complete control in the acute phase, the percentage of patients who achieved delayed complete control was higher in the gabapentin group (89.3 × 60.7%, p = 0.01). Adverse events did not significantly differ between study arms. CONCLUSIONS: Gabapentin is a low-cost strategy to improve complete control of CINV, specially delayed CINV control.

Serum cross-linked n-telopeptides of type 1 collagen (NTx) in patients with solid tumors.

CONTEXT AND OBJECTIVE: Cross-linked N-telopeptides of type I collagen (NTx) increase in concentration in situations in which bone resorption is increased, such as osteoporosis and bone metastasis (BM). We aimed to evaluate the serum concentrations of NTx in a sample of patients with several types of solid tumors. DESIGN AND SETTING: Cross-sectional analytical study with a control group in a tertiary public hospital. METHODS: We performed the quantitative enzyme-linked immunosorbent assay (ELISA) on serum NTx levels in 19 subjects without a history of cancer and 62 patients with various solid tumors who had been referred for a bone scan. Three experienced analysts read all bone scans. RESULTS: The serum NTx levels in patients with cancer and BM, with cancer but without BM and without cancer were 46.77 +/- 2.58, 32.85 +/- 2.05 and 22.32 +/- 2.90 respectively (P < 0.0001). We did not find any significant correlations of serum NTx with age, gender, history of bone pain, tumor type and bone alkaline phosphatase levels. We found a significant correlation between serum NTx and alkaline phosphatase levels (R(2) = 0.08; P = 0.022). CONCLUSIONS: Serum NTx levels are significantly higher in patients with solid tumors and bone metastases than they are in patients without bone metastases and in normal controls.

Serum cross-linked n-telopeptides of type 1 collagen (NTx) in patients with solid tumors / Dosagem sérica do N-telopeptídeo do colágeno tipo I (NTx) em pacientes com tumores sólidos

CONTEXT AND OBJECTIVE: Cross-linked N-telopeptides of type I collagen (NTx) increase in concentration in situations in which bone resorption is increased, such as osteoporosis and bone metastasis (BM). We aimed to evaluate the serum concentrations of NTx in a sample of patients with several types of solid tumors. DESIGN AND SETTING: Cross-sectional analytical study with a control group in a tertiary public hospital. METHODS: We performed the quantitative enzyme-linked immunosorbent assay (ELISA) on serum NTx levels in 19 subjects without a history of cancer and 62 patients with various solid tumors who had been referred for a bone scan. Three experienced analysts read all bone scans. RESULTS: The serum NTx levels in patients with cancer and BM, with cancer but without BM and without cancer were 46.77 ± 2.58, 32.85 ± 2.05 and 22.32 ± 2.90 respectively (P < 0.0001). We did not find any significant correlations of serum NTx with age, gender, history of bone pain, tumor type and bone alkaline phosphatase levels. We found a significant correlation between serum NTx and alkaline phosphatase levels (R² = 0.08; P = 0.022). CONCLUSIONS: Serum NTx levels are significantly higher in patients with solid tumors and bone metastases than they are in patients without bone metastases and in normal controls.

CONTEXTO E OBJETIVO: Os N-telopeptídeos do colágeno tipo-I (NTx) elevam-se quando a reabsorção óssea está aumentada, devido a condições como osteoporose e metástase óssea. Sendo assim, temos por objetivo avaliar os níveis séricos de NTx em uma população heterogênea de pacientes com tumores sólidos. TIPO DE ESTUDO E LOCAL: Estudo transversal analítico com grupo controle, realizado em hospital público terciário. MÉTODOS: 19 pacientes sem história de câncer e 62 pacientes com tumores sólidos de vários tipos, encaminhados para estadiamento e investigação dos sintomas esqueléticos, foram avaliados pela técnica de ELISA (Enzyme Linked Immuno Sorbent Assay) quantitativa para a dosagem de NTx. Três especialistas leram todas as imagens ósseas. RESULTADOS: O nível de NTx encontrado em pacientes com câncer e metástase óssea, sem metástase óssea e sem diagnóstico de câncer foi 46,77 ± 2,58, 32,85 ± 2,05 e 22,32 ± 2,90, respectivamente (P < 0,0001). Não encontramos correlação entre o NTx, idade, sexo, história de dor óssea, tipo de tumor e níveis de fosfatase alcalina óssea. Encontramos correlação significativa entre os níveis de NTx e de Fosfatase Alcalina (r² = 0,08, P = 0,022). CONCLUSÃO: O NTx sérico é significativamente mais elevado em pacientes com tumores sólidos e metástases ósseas quando comparado com pacientes sem metástases ósseas e controles normais.

Sensibilidade e especificidade da dosagem sérica do N-telopeptídeo do colágeno tipo I (NTx) em pacientes com tumores sólidos / Sensitivity and specificity of serum cross-linked N-telopeptides of type 1 collagen (NTx) in patients with solid tumors

Objetivo: Os N-telopeptídeos do colágeno tipo-I (NTx) se elevam quando a reabsorção óssea está aumentada, devido a condições como a osteoporose e a metástase óssea, sendo assim, o objetivo deste estudo foi avaliar a utilidade da dosagem de NTx em uma população heterogênea de pacientes com tumores sólidos para o diagnóstico de metástases ósseas. Métodos: Foi conduzido um estudo prospectivo em um hospital público terciário. Foram analisados 19 pacientes sem história de câncer e 62 pacientes com tumores sólidos de vários tipos, encaminhados para estadiamento e investigação dos sintomas esqueléticos. Utilizou-se a técnica de ELISA (enzyme-linked immunosorbent assay) quantitativa para a dosagem de NTx. Três especialistas leram todas as imagens ósseas, obtidas por medicina nuclear. Rresultados: Não foi encontrada correlação entre o NTx, idade, sexo, história de dor óssea, tipo de tumor e níveis de fosfatase alcalina óssea. Foi encontrada correlação significativa entre os níveis de NTx e de fosfatase alcalina (r² = 0,08, p = 0,022). Os valores preditivos positivo e negativo, assim como os valores de sensibilidade, especificidade e da curva ROC (receiver operating characteristic) para a presença de metástase óssea foram: 0,34, 0,92, 0,95, 0,22 e 0,59, respectivamente. Cconclusões: Concluiu-se que o NTx é altamente sensível para o diagnóstico de metástase óssea em pacientes com tumores sólidos e metástases ósseas.

A medical student-staffed outpatient oncology clinic: a 10-year Brazilian experience.

BACKGROUND: This is an update of a 10-years student-staffed oncology clinic. METHODS: Students are divided into 4 teams; each sees 1 to 2 outpatients weekly. RESULTS: By April 2006, 95 medical students participated, 89% for 2 or more years; 70% reported activity contributed to ability to read medical papers, and 59% improved their scientific writing. Of 39 students currently involved, 33 (84%) improved clinical skills in taking history, 27 (69%) in physical examination, and 34 (87%) in physician-patient relation. A total of 21 (56%) reported increased knowledge in general internal medicine. Although only 11% of former students pursued a specialty in Medical Oncology, 77% rated this clinic as the best extracurricular activity. CONCLUSIONS: Attendance of outpatient clinic in medical oncology can contribute significantly to the general medical education.

Adjunct dipyrone in association with oral morphine for cancer-related pain: the sooner the better.

INTRODUCTION: Adjunct nonopioid analgesics may improve pain control in patients with cancer needing morphine or its derivates. Dipyrone is a cheap nonopioid analgesic widely used in many countries. OBJECTIVE: The objective of the study was to evaluate, whenever morphine was started, if associating dipyrone with it would improve pain control and if this effect was time dependent. MATERIALS AND METHODS: This is a double-blind placebo-controlled randomized crossover study. Thirty-four ambulatory cancer patients experiencing cancer-related pain for which oral morphine was to be started at the dose of 10 mg orally (PO) every 4 h were randomized to take either dipyrone 500 mg PO every 6 h or placebo. After 48 h, patients would be switched from dipyrone to placebo and vice versa. Pain was the primary outcome and was measured using a visual analogue scale before starting medications, at 48 and 96 h. RESULTS: We randomized 16 patients to start with placebo (group 1) and 18 with dipyrone (group 2). Pain scores for groups 1 and 2 were at baseline: 7.31 +/- 0.29 vs 6.88 +/- 0.28 (p = 0.3), at 48 h: 7.06 +/- 0.32 vs 5.5 +/- 0.31 (p = 0.001), and at 96 h: 3.18 +/- 0.39 vs 1.94 +/- 0.37 (p = 0.03). Both groups had significant improvements in pain scores after introducing dipyrone (p < 0.001, for both). Main toxicities were nausea, vomiting, epigastric pain, and myalgias. Twenty-eight patients chose dipyrone, four placebo, and two were indifferent. CONCLUSIONS: We conclude that dipyrone adds significantly to the analgesic effect of morphine and, when given at the time of starting morphine, results in better pain scores even after dipyrone is discontinued.