Critical assessment of resource waste in staging and follow-up of breast cancer.

BACKGROUND: Breast cancer is a public health problem with both high incidence and cure rates. After treatment, patients are monitored for long periods of time due to the risk of recurrence. Thus, staging and follow-up strategies should consider not only the best results for the patient but also its costs for the public health system. OBJECTIVE: The objective of this study was to quantify the waste of resources on breast cancer follow-up and evaluate its impact on the public health system. METHODS: This is a retrospective analysis of consecutive medical records to identify the intervals between consultations and tests used for staging and during the first 2 years of follow-up of patients with breast cancer treated at a public hospital in Brazil. Data were compared with the guidelines of the main international consensus. RESULTS: Medical records of 60 consecutive patients treated in 2018 were selected, of whom 52 had 2 or more years of follow-up, and 8 had only 1 year of complete follow-up. A total of 34 patients (56.67%) underwent excessive examinations for stating. During follow-up, 125 surplus consultations were performed (33.6%). In this phase, 111 surplus exams were also performed, representing an increase of 100.9%. A total of 423 laboratory tests were performed for 18 patients in the first year and 229 tests for 14 patients in the second year. CONCLUSION: Excessive tests and consultations significantly burdened the Unified Health System without any benefit to patients. Better adherence to staging and follow-up recommendations could reduce costs and optimize the limited resources used in the public health system.

Critical assessment of resource waste in staging and follow-up of breast cancer

SUMMARY BACKGROUND: Breast cancer is a public health problem with both high incidence and cure rates. After treatment, patients are monitored for long periods of time due to the risk of recurrence. Thus, staging and follow-up strategies should consider not only the best results for the patient but also its costs for the public health system. OBJECTIVE: The objective of this study was to quantify the waste of resources on breast cancer follow-up and evaluate its impact on the public health system. METHODS: This is a retrospective analysis of consecutive medical records to identify the intervals between consultations and tests used for staging and during the first 2 years of follow-up of patients with breast cancer treated at a public hospital in Brazil. Data were compared with the guidelines of the main international consensus. RESULTS: Medical records of 60 consecutive patients treated in 2018 were selected, of whom 52 had 2 or more years of follow-up, and 8 had only 1 year of complete follow-up. A total of 34 patients (56.67%) underwent excessive examinations for stating. During follow-up, 125 surplus consultations were performed (33.6%). In this phase, 111 surplus exams were also performed, representing an increase of 100.9%. A total of 423 laboratory tests were performed for 18 patients in the first year and 229 tests for 14 patients in the second year. CONCLUSION: Excessive tests and consultations significantly burdened the Unified Health System without any benefit to patients. Better adherence to staging and follow-up recommendations could reduce costs and optimize the limited resources used in the public health system.

Cardiac Safety of the Trastuzumab Biosimilar ABP 980 in Women with HER2-Positive Early Breast Cancer in the Randomized, Double-Blind, Active-Controlled LILAC Study.

INTRODUCTION: Although the human epidermal growth factor receptor 2 (HER2) blocker trastuzumab is generally well tolerated, cardiotoxicity can be an important therapeutic limitation. OBJECTIVE: In this prespecified analysis, we compared the cardiac safety of the trastuzumab biosimilar ABP 980 (KANJINTI™) and the trastuzumab reference product (RP; Herceptin®) in the phase III LILAC study (ClinicalTrials.gov identifier NCT01901146). METHODS: In the neoadjuvant phase of LILAC, after run-in chemotherapy, 725 patients were randomized 1:1 to ABP 980 (n = 364) or trastuzumab RP (n = 361) plus paclitaxel (every 3 weeks [Q3W] or every week [QW]) for four cycles. After surgery, patients continued treatment Q3W for up to 1 year; ABP 980-treated patients continued ABP 980 (ABP 980/ABP 980; n = 364), and trastuzumab RP-treated patients either continued on the RP (trastuzumab RP/trastuzumab RP; n = 190) or switched to ABP 980 (trastuzumab RP/ABP 980; n = 171). Cardiac safety was monitored by computerized 12-lead electrocardiogram, and left ventricular ejection fraction (LVEF) was assessed by two-dimensional (2D) echocardiogram. LVEF decline was defined as LVEF value decrease from study baseline by ≥ 10 percentage points and to < 50%. RESULTS: Over the entire study, 22 (3.1%) patients had protocol-defined LVEF decline; no meaningful between-group differences were observed (ABP 980/ABP 980: 2.8%; trastuzumab RP/trastuzumab RP: 3.3%; trastuzumab RP/ABP 980: 3.5%). The incidence of cardiac adverse events was low and comparable in the treatment groups. One grade 3 cardiac failure event reported in the trastuzumab RP/ABP 980 arm, and another in the trastuzumab RP/trastuzumab RP arm, were coincident with LVEF decline. One patient discontinued the investigational product during the adjuvant phase because of cardiac failure. CONCLUSION: These prespecified analyses confirm the tolerability of ABP 980 and demonstrate clinical similarity of ABP 980 and trastuzumab RP with respect to cardiac safety. No new cardiac safety signals were observed whether patients were receiving ABP 980 or switched from the RP to ABP 980.

Totality of Scientific Evidence in the Development of ABP 980, a Biosimilar to Trastuzumab.

ABP 980 was developed as a biosimilar to trastuzumab, a monoclonal antibody targeting human epidermal growth factor receptor 2 (HER2), that is indicated for the treatment of HER2-positive metastatic breast cancer, early breast cancer (EBC), and metastatic gastric cancer. ABP 980 is approved in the United States, European Union, and Japan for all the indications of trastuzumab, based on the totality of evidence (TOE) gathered by the systematic step-wise accumulation of comparative analytical, preclinical, and clinical (pharmacokinetics [PK], efficacy, safety and immunogenicity) data for ABP 980 and trastuzumab reference product (RP). As a key first step of the ABP 980 biosimilar program, comprehensive analytical characterization of critical quality attributes established that ABP 980 is structurally and functionally similar to trastuzumab RP. Complementing these data, results of non-clinical pharmacology, toxicology, and toxicokinetic studies supported similarity between ABP 980 and trastuzumab RP. A randomized study in healthy subjects demonstrated clinical PK equivalence of ABP 980 relative to trastuzumab RP in these subjects. In the final clinical evaluation step, a randomized comparative study (LILAC) confirmed the lack of clinically meaningful differences between ABP 980 and trastuzumab RP in efficacy, safety, and immunogenicity in women with HER2-positive EBC in the neoadjuvant-adjuvant setting. Neoadjuvant EBC represented a sensitive homogenous population for biosimilar demonstrations, and the primary endpoint of pathologic complete response served as a sensitive surrogate endpoint. An important aspect of the LILAC study design is that it is the only study that evaluated the effect of switching from the trastuzumab RP to a trastuzumab biosimilar during the adjuvant phase. No new or unexpected safety signals emerged in the clinical evaluations, with the safety profile of ABP 980 consistent with that previously described for trastuzumab. Overall, the TOE data generated for ABP 980 support the conclusion that it is highly similar to trastuzumab RP, thus providing the scientific justification for extrapolation to all the approved indications of trastuzumab.

Efficacy and safety of ABP 980 compared with reference trastuzumab in women with HER2-positive early breast cancer (LILAC study): a randomised, double-blind, phase 3 trial.

BACKGROUND: ABP 980 (Amgen Inc, Thousand Oaks, CA, USA) is a biosimilar of trastuzumab, with analytical, functional, and pharmacokinetic similarities. We compared the clinical safety and efficacy of ABP 980 with that of trastuzumab in women with HER2-positive early breast cancer. METHODS: We did a randomised, multicentre, double-blind, active-controlled equivalence trial at 97 study centres in 20 countries, mainly in Europe and South America. Eligible women were aged 18 years or older, had histologically confirmed HER2-positive invasive early breast cancer, an Eastern Cooperative Oncology Group performance status score of 0 or 1, and were planning to have surgical resection of the breast tumour with sentinel or axillary lymph node dissection and neoadjuvant chemotherapy. After four cycles of run-in anthracycline-based chemotherapy, patients were assigned 1:1 to receive ABP 980 or trastuzumab with a permuted block design (blocks of four) computer-generated randomisation schedule. Patients received neoadjuvant therapy with a loading dose (8 mg/kg) of ABP 980 or trastuzumab plus paclitaxel 175 mg/m2 in a 90 min intravenous infusion, followed by three cycles of 6 mg/kg intravenous ABP 980 or trastuzumab plus paclitaxel 175 mg/m2 every 3 weeks in 30 min intravenous infusions (or 80 mg/m2 paclitaxel once per week for 12 cycles if that was the local standard of care). Randomisation was stratified by T stage, node status, hormone receptor status, planned paclitaxel dosing schedule, and geographical region. Surgery was completed 3-7 weeks after the last dose of neoadjuvant treatment, after which adjuvant treatment with ABP 980 or trastuzumab was given every 3 weeks for up to 1 year after the first dose in the study. Patients had been randomly assigned at baseline to continue APB 980, continue trastuzumab, or switch from trastuzumab to APB 980 as their adjuvant treatment. The co-primary efficacy endpoints were risk difference and risk ratio (RR) of pathological complete response in breast tissue and axillary lymph nodes assessed at a local laboratory in all patients who were randomly assigned and received any amount of neoadjuvant investigational product and underwent surgery. We assessed safety in all patients who were randomly assigned and received any amount of investigational product. This trial is registered with ClinicalTrials.gov, number NCT01901146 and Eudra, number CT 2012-004319-29. FINDINGS: Of 827 patients enrolled, 725 were randomly assigned to receive ABP 980 (n=364) or trastuzumab (n=361). The primary endpoint was assessable in 696 patients (358 who received ABP 980 and 338 who received trastuzumab). Pathological complete response was recorded in 172 (48%, 95% CI 43-53) of 358 patients in the ABP 980 group and 137 (41%, 35-46) of 338 in the trastuzumab group (risk difference 7·3%, 90% CI 1·2-13·4; RR 1·188, 90% CI 1·033-1·366), with the upper bounds of the CIs exceeding the predefined equivalence margins of 13% and 1·318, respectively. Pathological complete response in the central laboratory assessment was seen in 162 (48%) of 339 patients assigned to ABP 980 at baseline and 138 (42%) of 330 assigned to trastuzumab at baseline (risk difference 5·8%, 90% CI -0·5 to 12·0, and RR 1·142, 90% CI 0·993 to 1·312). Grade 3 or worse adverse events during the neoadjuvant phase occurred in 54 (15%) of 364 patients in the ABP 980 group and 51 (14%) of 361 patients in the trastuzumab group, of which the most frequent grade 3 or worse event of interest was neutropenia, occurring in 21 (6%) patients in both groups. In the adjuvant phase, grade 3 or worse adverse events occurred in 30 (9%) of 349 patients continuing ABP 980, 11 (6%) of 171 continuing trastuzumab, and 13 (8%) of 171 who switched from trastuzumab to ABP 980, the most frequent grade 3 or worse events of interest were infections and infestations (four [1%], two [1%], and two [1%]), neutropenia (three [1%], two [1%], and one [1%]), and infusion reactions (two [1%], two [1%], and three [2%]). Two patients died from adverse events judged to be unrelated to the investigational products: one died from pneumonia while receiving neoadjuvant ABP 980 and one died from septic shock while receiving adjuvant ABP 980 after trastuzumab. INTERPRETATION: Although the lower bounds of the 90% CIs for RR and risk difference showed non-inferiority, the upper bounds exceeded the predefined equivalence margins when based on local laboratory review of tumour samples, meaning that non-superiority was non-conclusive. In our sensitivity analyses based on central laboratory evaluation of tumour samples, estimates for the two drugs were contained within the predefined equivalence margins, indicating similar efficacy. ABP 980 and trastuzumab had similar safety outcomes in both the neoadjuvant and adjuvant phases of the study. FUNDING: Amgen.

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.

Intervención comunitaria para mejorar la calidad de vida del adulto mayor / Community intervention to improve the elderlyquality of life

Introducción: el incremento de la población longeva impone un reto al sistema de salud: identificar factores que contribuyan a incrementar la calidad de vida de este grupo etario. Objetivos: mostrar los resultados de una estrategia de intervención para mejorar los niveles de calidad de vida, en adultos mayores. Métodos: investigación con diseño prospectivo longitudinal y métodos cualitativos y de investigación acción en una muestra de 20 adultos mayores de un universo de 36 que asistieron al Taller de Transformación Integral, en Alamar, Municipio Habana del Este, de septiembre 2009 a enero del 2010. Resultados: se elevaron los niveles de calidad de vida en la mayoría de los adultos mayores estudiados, así como cambios importantes y favorables en la autoestima y en los estilos de vida con riesgo para la salud. Conclusiones: se mostró la eficacia del programa de intervención y su factibilidad(AU)

Introduction: The growing of aging population poses a challenge to the health system: identifying factors that contribute to increasing the quality of life for this age group. Objectives: Show the results of an intervention strategy for improving levels of quality of life in older adults. Methods: A prospective longitudinal research was conducted in a sample of 20 elderly in a universe of 36 who attended the Comprehensive Workshop on Transformationin Alamar, Habana del Este Municipality from September 2009 to January 2010. Results: The levels of quality of life are elevated in most elderly studied, as well as important and positive self-esteem and lifestyle with health risk changes. Conclusions: The effectiveness of the intervention program and its feasibility was shown(AU)

Intervención comunitaria para mejorar la calidad de vida del adulto mayor / Community intervention to improve the elderlyquality of life

Introducción: el incremento de la población longeva impone un reto al sistema de salud: identificar factores que contribuyan a incrementar la calidad de vida de este grupo etario.Objetivos: mostrar los resultados de una estrategia de intervención para mejorar los niveles de calidad de vida, en adultos mayores.Métodos: investigación con diseño prospectivo longitudinal y métodos cualitativos y de investigación acción en una muestra de 20 adultos mayores de un universo de 36 que asistieron al Taller de Transformación Integral, en Alamar, Municipio Habana del Este, de septiembre 2009 a enero del 2010.Resultados: se elevaron los niveles de calidad de vida en la mayoría de los adultos mayores estudiados, así como cambios importantes y favorables en la autoestima y en los estilos de vida con riesgo para la salud.Conclusiones: se mostró la eficacia del programa de intervención y su factibilidad(AU)

Adjuvant treatment delay in breast cancer patients.

BACKGROUND: to evaluate if time between surgery and the first adjuvant treatment (chemotherapy, radiotherapy or hormone therapy) in patients with breast cancer is a risk factor for lower overall survival (OS). METHOD: data from a five-year retrospective cohort study of all women diagnosed with invasive breast cancer at an academic oncology service were collected and analyzed. RESULTS: three hundred forty-eight consecutive women were included. Time between surgery and the first adjuvant treatment was a risk factor for shorter overall survival (HR=1.3, 95CI 1.06-1.71, p=0.015), along with negative estrogen receptor, the presence of lymphovascular invasion and greater tumor size. A delay longer than 4 months between surgery and the first adjuvant treatment was also associated with shorter overall survival (cumulative survival of 80.9% for delays ≤ 4 months vs. 72.6% for delays > 4 months; p=0.041, log rank test). CONCLUSION: each month of delay between surgery and the first adjuvant treatment in women with invasive breast cancer increases the risk of death in 1.3-fold, and this effect is independent of all other well-established risk factors. Based on these results, we recommend further public strategies to decrease this interval.

Applicability of modified Glasgow Prognostic Score in the assessment of elderly patients with cancer: A pilot study.

OBJECTIVES: To evaluate the relationship between inflammatory parameters through the modified Glasgow Prognostic Score (mGPS) and other clinical characteristics of elderly patients with cancer, including frailty evaluated by the Edmonton Frailty Scale (EFS). MATERIALS AND METHODS: We included patients from the oncology service at Faculdade de Medicina do ABC with a confirmed diagnosis of solid tumor aged 65 years or more at diagnosis. Patients were assessed by applying the translated and validated to Portuguese version of the EFS and also had blood sample collection for the evaluation of C-reactive protein (CRP) and albumin for calculation of the mGPS. RESULTS: We included 52 patients of both sexes, with median age of 72.5 years, of these 67.3% had localized disease and 32.7% metastatic disease. The mGPS presented 17.3% of high-risk patients. The frailty evaluated by EFS occurred in 57.6% of patients. Patients with both abnormal parameters (CRP and albumin) in the mGPS had significantly higher scores on EFS when compared to those with no change (6 vs. 9.56 points, p=0.021). The mGPS correlated also with clinical staging (p=0.019) and performance status (p=0.039). CONCLUSIONS: Inflammatory parameters correlate significantly with frailty, more advanced clinical stage and poor functional status.

Adjuvant treatment delay in breast cancer patients / Atraso no tratamento adjuvante em pacientes com câncer de mama

Summary Background: to evaluate if time between surgery and the first adjuvant treatment (chemotherapy, radiotherapy or hormone therapy) in patients with breast cancer is a risk factor for lower overall survival (OS). Method: data from a five-year retrospective cohort study of all women diagnosed with invasive breast cancer at an academic oncology service were collected and analyzed. Results: three hundred forty-eight consecutive women were included. Time between surgery and the first adjuvant treatment was a risk factor for shorter overall survival (HR=1.3, 95CI 1.06-1.71, p=0.015), along with negative estrogen receptor, the presence of lymphovascular invasion and greater tumor size. A delay longer than 4 months between surgery and the first adjuvant treatment was also associated with shorter overall survival (cumulative survival of 80.9% for delays ≤ 4 months vs. 72.6% for delays > 4 months; p=0.041, log rank test). Conclusion: each month of delay between surgery and the first adjuvant treatment in women with invasive breast cancer increases the risk of death in 1.3-fold, and this effect is independent of all other well-established risk factors. Based on these results, we recommend further public strategies to decrease this interval.

Resumo Objetivo: avaliar se o tempo da cirurgia até o primeiro tratamento adjuvante (quimioterapia, radioterapia ou hormonioterapia) em pacientes com câncer de mama é um fator de risco para pior sobrevivência global (SG). Métodos: estudo retrospectivo em que foram coletados dados dos prontuários de todas as mulheres com câncer de mama invasivo, diagnosticadas entre janeiro de 2005 e dezembro de 2010, atendidas consecutivamente em um serviço acadêmico de oncologia. Resultados: foram incluídas 348 mulheres, com mediana de tempo entre a cirurgia e o primeiro tratamento adjuvante de 2 meses. A sobrevivência global foi pior entre as mulheres com maior tempo entre a cirurgia e o primeiro tratamento adjuvante. Após análise multivariada, essa variável permaneceu como fator de risco independente para SG, juntamente com receptor de estrógeno negativo, presença de invasão angiolinfática e maior tamanho tumoral. Conclusão: o tempo entre a cirurgia e o primeiro tratamento adjuvante é um fator de risco independente para a sobrevivência global de mulheres com câncer de mama invasivo.

Uncaria tomentosa (cat's claw) improves quality of life in patients with advanced solid tumors.

OBJECTIVE: Cat's claw (Uncaria tomentosa) is a native Amazon plant that exhibits anti-inflammatory and antitumor properties. We wanted to assess its activity for symptom management of terminal cancer patients. METHODS: This prospective phase II study assessed the effects of a 100-mg dose of a dry extract of U. tomentosa three times per day in patients with advanced solid tumors who had no further therapeutic options and a life expectancy of at least 2 months. The European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ C30) and Functional Assessment of Chronic Illness Therapy - Fatigue questionnaires were used to assess the participants' quality of life, the Hospital Anxiety and Depression Scale questionnaire was used to assess anxiety and depression, and the Pittsburgh Sleep Quality Index was used to assess sleep quality. In addition, several biochemical and inflammatory parameters were analyzed. RESULTS: Fifty-one volunteers were recruited. Their median age was 64 (range, 33-85) years, and 47% of patients were female. More than 65% of patients had scores on the Karnofsky Performance Scale of 80% or less. Treatment improved the patients' overall quality of life (p=0.0411) and social functioning (p=0.0341), as assessed by the EORTC QLQ C-30, and reduced fatigue (p=0.0496) according to the Chalder Fatigue Questionnaire. None of the biochemical or inflammatory parameters assessed (interleukin-1 and -6, C-reactive protein, tumor necrosis factor-α, erythrocyte sedimentation rate, and α-1-acid glycoprotein) changed significantly. No tumor response was detected according to the Response Evaluation Criteria In Solid Tumors; however, the disease stabilized for more than 8 months in four participants. The medication was well tolerated by most patients. CONCLUSION: Use of cat's claw might be beneficial in patients with advanced cancer by improving their quality of life and reducing fatigue. The mechanism of action does not seem to be related to the anti-inflammatory properties of this plant.

Paullinia cupana para o controle de fogachos em pacientes com câncer de mama: um estudo piloto / Paullinia cupana for control of hot flashes in breast cancer patients: a pilot study

OBJETIVO: Avaliar se a Paullinia cupana diminui o número e a gravidade dos fogachos em mulheres após diagnóstico de câncer de mama. MÉTODOS: Estudo piloto prospectivo fase II realizado com mulheres que sobreviveram ao câncer de mama, que completaram o tratamento pelo menos 3 meses antes e que apresentavam ao menos 14 episódios de fogachos por semana. Utilizando o desenho de Simon para que a primeira etapa fosse considerada positiva, ao menos 9 de 15 mulheres deveriam ter a gravidade dos fogachos diminuída em pelo menos 50%. As pacientes receberam 50mg do extrato seco de Guaraná oralmente 2 vezes por dia por 6 semanas. Foram avaliadas, a gravidade e a frequência dos fogachos. RESULTADOS: Dezoito pacientes iniciaram o tratamento com Paullinia cupana e 15 completaram o estudo. Três pacientes deixaram o estudo imediatamente após iniciarem o tratamento em razão de dificuldade na participação e não adesão. Das 15 pacientes que completaram o estudo, 10 obtiveram diminuição de mais de 50% dos índices de gravidade de fogachos. Durante as 6 semanas de tratamento, diminuições estatisticamente significativas foram observadas tanto no número de fogachos (p=0,0009), quanto nos índices de gravidade (p<0,0001). Paullinia cupana foi bem tolerada, e não houve relato de toxicidade como causa de saída do estudo. CONCLUSÕES: Paullinia cupana pareceu promissora para o controle de fogachos. Estudos mais extensivos são necessários.

OBJECTIVE: To evaluated whether Paullinia cupana decrease number and severity of hot flashes in breast cancer survivors. METHODS: This was a prospective phase II pilot study. We studied female breast cancer survivors who had completed the cancer treatment 3 months previously and who were experiencing at least 14 hot flashes per week. At least 9 of the 15 patients were required to have a decrease of at least 50% in hot flash severity score in keeping with the Simon Design. Patients received 50mg of dry extract of Paullinia cupana orally twice a day for 6 weeks. We assessed both frequency and severity of hot flashes. RESULTS: A total of 18 patients started the Paullinia cupana treatment, and 15 completed the study. Three patients left the study immediately after starting the treatment because of personal difficulties in participation or noncompliance. Of the 15 patients who completed the study 10 had a decrease of more than 50% in hot flash severity scores. During the 6 weeks of treatment, statistically significant decreases were seen in both numbers of hot flashes (p=0.0009) and severity scores (p<0.0001). Paullinia cupana was well tolerated, and there were no instances of discontinuation because of toxicity. CONCLUSIONS: Paullinia cupana appears promising for controlling hot flashes. More extensive studies seem warranted.

Paullinia cupana for control of hot flashes in breast cancer patients: a pilot study.

OBJECTIVE: To evaluated whether Paullinia cupana decrease number and severity of hot flashes in breast cancer survivors. METHODS: This was a prospective phase II pilot study. We studied female breast cancer survivors who had completed the cancer treatment 3 months previously and who were experiencing at least 14 hot flashes per week. At least 9 of the 15 patients were required to have a decrease of at least 50% in hot flash severity score in keeping with the Simon Design. Patients received 50mg of dry extract of Paullinia cupana orally twice a day for 6 weeks. We assessed both frequency and severity of hot flashes. RESULTS: A total of 18 patients started the Paullinia cupana treatment, and 15 completed the study. Three patients left the study immediately after starting the treatment because of personal difficulties in participation or noncompliance. Of the 15 patients who completed the study 10 had a decrease of more than 50% in hot flash severity scores. During the 6 weeks of treatment, statistically significant decreases were seen in both numbers of hot flashes (p=0.0009) and severity scores (p<0.0001). Paullinia cupana was well tolerated, and there were no instances of discontinuation because of toxicity. CONCLUSIONS: Paullinia cupana appears promising for controlling hot flashes. More extensive studies seem warranted.

Factores de riesgo para la salud familiar: acontecimientos significativos / Risk factors for family health: significative events

El trabajo aborda el estudio de aquellos acontecimientos que pueden generar crisis familiares. Se define el concepto de acontecimiento significativo de la vida familiar y se establece una diferenciación de estos con las crisis familiares. Se realiza un recorrido por las diferentes etapas que atraviesa el ciclo de vida familiar y de los acontecimientos significativos que constituyen momentos de riesgo en éste.

This work deals with the study of those events that can generate family crises. The concept of significative event of the family life is defined, and it is established a difference between them and the family crises. The different stages through which the family life passes by and the significative events that constitute risk peaks within this cycle are analyzed.

Tegafur-uracil is a safe alternative for the treatment of colorectal cancer in patients with partial dihydropyrimidine dehydrogenase deficiency: a proof of principle.

OBJECTIVE: The objective of this study was to evaluate the safety of using tegafur-uracil (UFT) in colorectal cancer patients with partial dihydropyrimidine dehydrogenase (DPD) deficiency. PATIENTS AND METHODS: The study included five colorectal cancer patients who presented with acute toxicity (grades 3 and 4) after being given the first cycle of chemotherapy using 5-fluorouracil. The DPD deficiency was confirmed by gene sequencing. After a full recovery from all side effects, we changed the regimen to UFT (300 mg/m(2)/day) associated with leucovorin (90 mg/day) for 21 days, with an empirical dose reduction of at least 10% in the first cycle. RESULTS: We prospectively analysed 22 UFT cycles in 5 patients. We did not observe any episodes of grade 3 or 4 toxicity. The predominant toxicities were of grades 1 and 2 (nausea, vomiting and diarrhoea). CONCLUSION: Here, we demonstrate a complete absence of severe toxicity in all patients and cycles analysed. We believe that UFT is a safe alternative for the treatment of patients with partial DPD deficiency.

Metástase meníngea em adulto jovem com sarcoma de Ewing da tíbia direita / Meningeal metastasis in young adult with Ewing´s sarcoma of the right tibia

Introdução: O sarcoma de Ewing representa 10% dos tumores ósseos, com predomínio no sexo masculino. A maior incidência é dos 5 aos 14 anos. Acomete mais as extremidades e em 25% dos casos há metástases ao diagnóstico. O acometimento do sistema nervoso central ocorre em 3% dos pacientes. A infiltração das leptomeninges é rara e ocorre predominantemente por contiguidade de uma lesão óssea subjacente. Relato do caso: Mulher de 27 anos com lesão em tíbia direita de 17 cm. A biópsia diagnosticou sarcoma de Ewing. Estadiamento sistêmico foi negativo e planejada quimioterapia neoadjuvante com esquema VAC-IE para preservação do membro. Após o primeiro ciclo de VAC teve neutropenia precoce, infecção de sítio tumoral, sepse e síndrome compartimental do membro. Submetida a amputação suprapatelar. Após 30 dias apresentou paralisia do VII, VI e III pares cranianos à esquerda e VII e III à direita, tomografia computadorizada do crânio foi normal e o líquor confirmou infiltração meníngea. A paciente evoluiu a óbito três dias após o diagnóstico de metástase meníngea. Discussão: A literatura é escassa em informações sobre a frequência do envolvimento meníngeo no sarcoma de Ewing. A forma peculiar do acometimento neste caso, sem metástase óssea que invadisse o sistema nervoso por contiguidade, faz-nos concluir que tal disseminação ocorreu pela via hematogênica. A paciente apresentava fatores de mau prognóstico (tumor > 100ml, idade > 26 anos, intervalo diagnóstico-metástases < 2 anos). O acometimento meníngeo contribuiu para o desfecho desfavorável, pois é um local de difícil controle da doença, considerado um santuário.

Câncer de Mama 2 - Resenha / Breast Cancer 2 - Review

Background: Analysis of the Austrian Breast and Colorectal Cancer Study Group trial-12 (ABCSG-12) at 48 months’ follow-up showed that addition of zoledronic acid to adjuvant endocrine therapy significantly improved disease-free survival. We have now assessed long-term clinical efficacy including disease-free survival and disease outcomes in patients receiving anastrozole or tamoxifen with or without zoledronic acid. Methods: ABSCG-12 is a randomised, controlled, open-label, two-by-two factorial, multicentre trial in 1803 premenopausal women with endocrine-receptor-positive early-stage (stage I-II) breast cancer receiving goserelin (3•6 mg every 28 days), comparing the efficacy and safety of anastrozole (1 mg per day) or tamoxifen (20 mg per day) with or without zoledronic acid (4 mg every 6 months) for 3 years. Randomisation (1:1:1:1 ratio) was computerised and based on the Pocock and Simon minimisation method to balance the four treatment arms across eight prognostic variables (age, neoadjuvant chemotherapy, pathological tumour stage; lymph-node involvement, type of surgery or locoregional therapy, complete axillary dissection, intraoperative radiation therapy, and geographical region). Treatment allocation was not masked. The primary endpoint was disease-free survival (defined as disease recurrence or death) and analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00295646; follow-up is ongoing. Findings: At a median follow-up of 62 months (range 0-114•4 months), more than 2 years after treatment completion, 186 disease-free survival events had been reported (53 events in 450 patients on tamoxifen alone, 57 in 453 patients on anastrozole alone, 36 in 450 patients on tamoxifen plus zoledronic acid, and 40 in 450 patients on anastrozole plus zoledronic acid).