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BACKGROUND: Bone metastasis (BM) is the most common site of disease in metastatic breast cancer (MBC) patients. BM impacts health-related quality of life (HRQoL). We tested prospectively the psychometric properties of the Bone Metastasis Quality of Life (BOMET-QoL-10) measure on MBC patients with BM. METHODS: Patients completed the BOMET-QoL-10 questionnaire, the Visual Analogue Scale (VAS) for pain, and a self-perceived health status item at baseline and at follow-up visits. We performed psychometric tests and calculated the effect size of specific BM treatment on patients´ HRQoL. RESULTS: Almost 70% of the 172 patients reported symptoms, 23.3% experienced irruptive pain, and over half were receiving chemotherapy. BOMET-QoL-10 proved to be a quick assessment tool performing well in readability and completion time (about 10 min) with 0-1.2% of missing/invalid data. Although BOMET-QoL-10 scores remained fairly stable during study visits, differences were observed for patient subgroups (e.g., with or without skeletal-related events or adverse effects). Scores were significantly correlated with physician-reported patient status, patient-reported pain, symptoms, and perceived health status. BOMET-QoL-10 scores also varied prospectively according to changes in pain intensity. CONCLUSIONS: BOMET-QoL-10 performed well as a brief, easy-to-administer, useful, and sensitive HRQoL measure for potential use for clinical practice with MBC patients. TRIAL REGISTRATION: NCT03847220. Retrospectively registered on clinicaltrials.gov (February the 20th 2019).
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INTRODUCTION: An increase in the number of cancer cases is expected in the near future. Breast cancer (BC) mortality rates increase with age even when adjusted for other variables. Here we analyzed BC disease-free survival (BCDFS) and BC specific survival (BCSS) in the El Alamo III BC registry of GEICAM Spanish Breast Cancer Group. MATERIALS AND METHODS: El Alamo III is a retrospective registry of BC patients diagnosed between 1998 and 2001. Patients with stage I-III invasive BC of age groups 55-64 years (y), 70-74 years and ≥ 75 years were included. Patients and tumors characteristics, treatments and recurrences and deaths were analyzed. RESULTS: 4343 patients were included within the following age intervals: 2288 (55-64 years), 960 (70-74 years), and 1095 (≥ 75 years). Older patients (≥ 70 years) were diagnosed with more advanced tumors (stage III) than younger patients (21.5% versus 13.4%, p < 0.0001). Mastectomies were performed more on older patients and they received less chemotherapy than younger patients (66.6% versus 43.1%, p < 0.00001 and 30.8% versus 71.6%, p < 0.0001, respectively). With a median follow-up of 5.9 years, 17.7% patients had BCDFS events in the younger group and 19.8% in the older group (p < 0.0001). A decrease in BCSS was also observed in older patients, either when analyzing patients ≥ 70y (p < 0.0001) and when differentiating by the two older groups (p < 0.0001). CONCLUSIONS: Our study suggests that older BC patients have worse outcomes what can be a consequence of receiving inadequate adjuvant treatments. Specific trials for these patients are warranted to allow us to treat them with the same scientific rigor than younger patients.
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Neoplasias de la Mama/mortalidad , Sistema de Registros/estadística & datos numéricos , Factores de Edad , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/química , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Supervivientes de Cáncer , Causas de Muerte , Quimioterapia Adyuvante/estadística & datos numéricos , Supervivencia sin Enfermedad , Femenino , Humanos , Mastectomía/estadística & datos numéricos , Persona de Mediana Edad , Recurrencia Local de Neoplasia , España/epidemiología , Análisis de SupervivenciaRESUMEN
PURPOSE: To evaluate the efficacy and safety of oral weekly vinorelbine 60 mg/m2 for metastatic breast cancer (MBC) in patients previously treated with anthracyclines or taxanes in routine clinical practice. MATERIALS AND METHODS: Fifty-five patients were enrolled in a prospective multicentre study conducted in Spain. Women ≥ 18 years of age with locally advanced breast cancer who were not candidates for surgical treatment with a radical intention or patients with stage IV disease, and who had received a prior taxane or anthracycline regimen were eligible for participation. RESULTS: Median age was 67 years. Median progression-free survival was 3.7 months (95% CI 2.5-4.9), median overall survival 10 months (95% CI 6.6-13.5), and overall response rate and clinical benefit rate were 29.1% and 49.1%, respectively. Main grade 3 and 4 toxicities were neutropenia 9.1%, febrile neutropenia 3.6% and constipation 3.6%. In total, 86% of the patients received complete treatment without delays or dose reduction. Moreover, HER2-positive patients who received oral vinorelbine concomitantly with trastuzumab showed better response (complete response: HER2-positive 14.3% vs. HER2-negative 0%; partial response: HER2-positive 42.9% vs. HER2-negative 25.6%; p = 0.008), better disease control rate (HER2-positive 100% vs. HER2-negative 46.2%; p = 0.011), and better values for the remaining analysed variables than HER2-negative patients. CONCLUSION: Our study provides real-world data on the use of oral weekly vinorelbine, which proves an effective and well-tolerated regimen for MBC patients previously treated with taxanes or anthracyclines. Patients with HER2-positive disease could also benefit from this treatment in combination with trastuzumab.
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Antineoplásicos Fitogénicos/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Vinorelbina/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Antraciclinas/administración & dosificación , Antraciclinas/farmacología , Antineoplásicos Fitogénicos/efectos adversos , Neoplasias de la Mama/metabolismo , Esquema de Medicación , Resistencia a Antineoplásicos , Femenino , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Estudios Prospectivos , Receptor ErbB-2/metabolismo , España , Análisis de Supervivencia , Taxoides/administración & dosificación , Taxoides/farmacología , Trastuzumab/administración & dosificación , Resultado del Tratamiento , Vinorelbina/efectos adversosRESUMEN
Purpose. To converge on an expert opinion to define aggressive disease in patients with HER2-negative mBC using a modified Delphi methodology. Methods. A panel of 21 breast cancer experts from the Spanish Society of Medical Oncology agreed upon a survey which comprised 47 questions that were grouped into three sections: relevance for defining aggressive disease, aggressive disease criteria and therapeutic goals. Answers were rated using a 9-point Likert scale of relevance or agreement. Results. Among the 88 oncologists that were invited to participate, 81 answered the first round (92%), 70 answered the second round (80%), and 67 answered the third round (76%) of the survey. There was strong agreement regarding the fact that identifying patients with aggressive disease needs to be adequately addressed to help practitioners to decide the best treatment options for patients with HER2-negative mBC. The factors that were considered to be strongly relevant to classifying patients with aggressive HER2-negative mBC were a high tumor burden, a disease-free interval of less than 12-24 months after surgery, the presence of progressive disease during adjuvant or neoadjuvant chemotherapy and having a triple-negative phenotype. The main therapeutic goals were controlling symptoms, improving quality of life and increasing the time to progression and overall survival. Conclusions. High tumor burden, time to recurrence after prior therapy and having a triple-negative phenotype were the prognostic factors for which the greatest consensus was found for identifying patients with aggressive HER2-negative mBC. Identifying patients with aggressive disease leads to different therapeutic approaches (AU)
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Humanos , Femenino , Neoplasias de la Mama/diagnóstico , Metástasis de la Neoplasia/diagnóstico , Conferencias de Consenso como Asunto , Biomarcadores de Tumor/normas , Receptor ErbB-2/análisis , Receptor ErbB-2/genética , Sociedades Médicas/normas , Oncología Médica/educación , Metástasis de la Neoplasia/tratamiento farmacológico , Oncología Médica , Oncología Médica/normasRESUMEN
Purpose. The SEOM Future Plan is aimed at identifying the main challenges, trends and needs of the medical oncology speciality over the next years, including potential oncologist workforce shortages, and proposing recommendations to overcome them. Methods. The estimations of the required medical oncologists workforce are based on an updated Medical Oncologist Register in Spain, Medical Oncology Departments activity data, dedication times and projected cancer incidence. Challenges, needs and future recommendations were drawn from an opinion survey and an advisory board. Results. A shortage of 211 FTE medical oncologist specialists has been established. To maintain an optimal ratio of 158 new cases/FTE, medical oncology workforce should reach 1881 FTE by 2035. Conclusions. Main recommendations to face the growing demand and complexity of oncology services include a yearly growth of 2.5% of medical oncologists workforce until 2035, and development and application of more accurate quality indicators for cancer care and health outcomes measure (AU)
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Humanos , Masculino , Femenino , Oncología Médica , Oncología Médica/organización & administración , Sociedades Médicas/organización & administración , Sociedades Médicas/normas , Servicio de Oncología en Hospital/organización & administración , Servicio de Oncología en Hospital/normas , Oncología Médica/ética , Oncología Médica/normas , Sociedades Médicas/ética , EspañaRESUMEN
Purpose. The Spanish Society of Medical Oncology (SEOM) has conducted a study on the access to oncologic drugs across the 17 Spanish Regions with the aim of identifying potential heterogeneities and making proposals for eliminating the barriers identified at the different levels. Methods. An Expert Panel made up of medical oncologists designed a survey on certain indications approved for 11 drugs in the approach of breast cancer, melanoma, lung cancer, prostate cancer and support treatment. This survey was sent to 144 National Health System (NHS) hospitals. Results. 77 hospitals answered the survey. The information modules analysed were: scope of the Commission that establishes binding decisions related to drug access; conditions, stages and periods of drug application, approval and administration processes; barriers to accessing drugs. Conclusions. The study shows variability in drug access. The SEOM makes proposals addressed to reducing the differences identified and homogenizing drug access conditions (AU)
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Humanos , Masculino , Femenino , Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéutico , Servicio de Oncología en Hospital/normas , Sociedades Médicas/organización & administración , Sociedades Médicas/normas , Sistemas de Salud/organización & administración , Sistemas de Salud/normas , Instituciones Oncológicas/organización & administración , Instituciones Oncológicas/normas , Disparidades en el Estado de Salud , Disparidades en el Estado de Salud , Encuestas y Cuestionarios/normas , Encuestas y Cuestionarios , Antineoplásicos/análisisRESUMEN
PURPOSE: To converge on an expert opinion to define aggressive disease in patients with HER2-negative mBC using a modified Delphi methodology. METHODS: A panel of 21 breast cancer experts from the Spanish Society of Medical Oncology agreed upon a survey which comprised 47 questions that were grouped into three sections: relevance for defining aggressive disease, aggressive disease criteria and therapeutic goals. Answers were rated using a 9-point Likert scale of relevance or agreement. RESULTS: Among the 88 oncologists that were invited to participate, 81 answered the first round (92%), 70 answered the second round (80%), and 67 answered the third round (76%) of the survey. There was strong agreement regarding the fact that identifying patients with aggressive disease needs to be adequately addressed to help practitioners to decide the best treatment options for patients with HER2-negative mBC. The factors that were considered to be strongly relevant to classifying patients with aggressive HER2-negative mBC were a high tumor burden, a disease-free interval of less than 12-24 months after surgery, the presence of progressive disease during adjuvant or neoadjuvant chemotherapy and having a triple-negative phenotype. The main therapeutic goals were controlling symptoms, improving quality of life and increasing the time to progression and overall survival. CONCLUSIONS: High tumor burden, time to recurrence after prior therapy and having a triple-negative phenotype were the prognostic factors for which the greatest consensus was found for identifying patients with aggressive HER2-negative mBC. Identifying patients with aggressive disease leads to different therapeutic approaches.
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Neoplasias de la Mama/clasificación , Neoplasias de la Mama/patología , Oncología Médica/normas , Consenso , Técnica Delphi , Femenino , Humanos , Receptor ErbB-2 , Sociedades MédicasRESUMEN
PURPOSE: The SEOM Future Plan is aimed at identifying the main challenges, trends and needs of the medical oncology speciality over the next years, including potential oncologist workforce shortages, and proposing recommendations to overcome them. METHODS: The estimations of the required medical oncologists workforce are based on an updated Medical Oncologist Register in Spain, Medical Oncology Departments activity data, dedication times and projected cancer incidence. Challenges, needs and future recommendations were drawn from an opinion survey and an advisory board. RESULTS: A shortage of 211 FTE medical oncologist specialists has been established. To maintain an optimal ratio of 158 new cases/FTE, medical oncology workforce should reach 1881 FTE by 2035. CONCLUSIONS: Main recommendations to face the growing demand and complexity of oncology services include a yearly growth of 2.5% of medical oncologist's workforce until 2035, and development and application of more accurate quality indicators for cancer care and health outcomes measure.
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Necesidades y Demandas de Servicios de Salud , Oncología Médica , Neoplasias/prevención & control , Oncólogos , Planificación de Atención al Paciente/normas , Humanos , EspañaRESUMEN
Anthracycline and taxane-based primary chemotherapy (PCT) is the standard treatment for high-risk breast cancer (HRBC). However, conventional anthracyclines are not commonly used in elderly patients or those prone to cardiotoxicity. Pegylated liposomal doxorubicin, (PLD) has comparable efficacy, but less cardiotoxicity than conventional anthracyclines. We conducted a phase II single-arm trial to assess the efficacy and safety of PCT based on PLD followed by paclitaxel (PTX) in a HRBC population usually undertreated. Fifty patients with stage II-IIIB breast cancer and at least one risk factor for developing cardiotoxicity initiated PLD 35 mg/m(2) plus cyclophosphamide 600 mg/m(2) every 4 weeks for four cycles, followed by 80 mg/m(2) weekly PTX for 12. Close cardiac monitoring was performed. Primary endpoint was the pathological complete response rate (pCR) in the breast. Treatment delivery and toxicities were assessed. Eighty-four per cent of patients were older than 65 years, 64 % suffered from hypertension, and 10 % had prior cardiac disease. In an intention-to-treat analysis, breast pCR was 32 % (95 % CI 19.5-46.7 %) and pCR in breast and axilla was 24 % (95 % CI 12.1-35.8 %). At diagnosis only, 26 % of patients were candidates for breast conservative surgery, which increased to 58.7 % after PCT. No significant decrease in left ventricular ejection fraction was seen. PLD followed by PTX was feasible in a fragile population of patients who were not candidates for conventional doxorubicin. Moreover, it achieved a pCR similar to standard therapy and could therefore be an option for elderly patients or cardiotoxicity-prone who present HRBC.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Biomarcadores de Tumor , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Cardiotoxicidad , Comorbilidad , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Doxorrubicina/análogos & derivados , Femenino , Cardiopatías/diagnóstico , Cardiopatías/etiología , Cardiopatías/fisiopatología , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Paclitaxel/administración & dosificación , Polietilenglicoles/administración & dosificación , Factores de Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND: Nonpegylated liposomal doxorubicin liposomal doxorubicin, (Myocet™; Sopherion Therapeutics, Inc Canada, and Cephalon, Europe) (NPLD; Myocet(®)) in combination with trastuzumabHerceptin(®) (Hoffmann-La Roche) has shown promising activity and cardiac safety. We conducted a randomized phase III trial of first-line NPLD plus trastuzumab and paclitaxel (Pharmachemie B.V.) (MTP) versus trastuzumab plus paclitaxel (TP) in patients with human epidermal growth factor 2 receptor (HER2)-positive metastatic breast cancer. PATIENTS AND METHODS: Patients were randomly assigned to NPLD (M, 50 mg/m(2) every 3 weeks for six cycles), trastuzumab (T, 4 mg/kg loading dose followed by 2 mg/kg weekly), and paclitaxel (P, 80 mg/m(2) weekly) or T + P at the same doses until progression or toxicity. The primary efficacy outcome was progression-free survival (PFS). RESULTS: One hundred and eighty-one patients were allocated to receive MTP, and 183 to TP. Median PFS was 16.1 and 14.5 months with MTP and TP, respectively [hazard ratio (HR) 0.84; two-sided P = 0.174]. In patients with estrogen receptor (ER)- and progesterone receptor (PR)-negative tumors, PFS was 20.7 and 14.0 months, respectively [HR 0.68; 95% confidence interval (CI) 0.47-0.99]. Median overall survival (OS) was 33.6 and 28.9 months with MTP and TP, respectively (HR 0.79; two-sided P = 0.083). In ER- and PR-negative tumors, OS was 38.2 and 27.9 months, respectively (HR 0.63; 95% CI 0.42-0.93). The frequency of adverse events was higher with MTP, but there was no significant difference in cardiac toxicity between treatment arms. CONCLUSION(S): The trial failed to demonstrate a significant clinical improvement with the addition of M to TP regimen. The clinical benefit observed in an exploratory analysis in the ER- and PR-negative population deserves consideration for further clinical trials. CLINICAL TRIAL NUMBER: NCT00294996.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Doxorrubicina/análogos & derivados , Paclitaxel/uso terapéutico , Receptor ErbB-2/metabolismo , Antibióticos Antineoplásicos/efectos adversos , Antibióticos Antineoplásicos/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Antineoplásicos Fitogénicos/efectos adversos , Antineoplásicos Fitogénicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Supervivencia sin Enfermedad , Doxorrubicina/efectos adversos , Doxorrubicina/uso terapéutico , Esquema de Medicación , Femenino , Humanos , Metástasis de la Neoplasia/tratamiento farmacológico , Paclitaxel/efectos adversos , Polietilenglicoles/efectos adversos , Polietilenglicoles/uso terapéutico , Estudios Prospectivos , Trastuzumab , Resultado del TratamientoRESUMEN
Insights into tumour biology of breast cancer have led the path towards the introduction of targeted treatment approaches; still, breast cancer-related mortality remains relatively high. Efforts in the field of basic research revealed new druggable targets which now await validation within the context of clinical trials. Therefore, questions concerning the optimal design of future studies are becoming even more pertinent. Aspects such as the ideal end point, availability of predictive markers to identify the optimal cohort for drug testing, or potential mechanisms of resistance need to be resolved. An expert panel representing the academic community, the pharmaceutical industry, as well as European Regulatory Authorities met in Vienna, Austria, in November 2012, in order to discuss breast cancer biology, identification of novel biological targets and optimal drug development with the aim of treatment individualization. This article summarizes statements and perspectives provided by the meeting participants.
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Receptor ErbB-2/genética , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/terapia , Ensayos Clínicos como Asunto , Femenino , Humanos , Terapia Molecular Dirigida , Transducción de Señal , Neoplasias de la Mama Triple Negativas/clasificación , Neoplasias de la Mama Triple Negativas/genéticaRESUMEN
PURPOSE: The primary aim of this trial was to assess the rate of pathologic complete responses (pCR) of doxorubicin/cyclophosphamide (AC) followed by bevacizumab/docetaxel (BT), as neoadjuvant therapy for breast cancer (BC). Furthermore, the association between biomarkers and the pCR was explored. METHODS: Patients with HER-negative operable stage II-III BC ≥ 2 cm were enrolled. Four cycles of AC (A 60 mg/m(2) and C 600 mg/m(2), every 3 weeks) followed by 4 cycles of BT (B 15 mg/kg and T 75 mg/m(2), every 3 weeks), were planned. A core-biopsy was performed for biological markers assessment. RESULTS: Seventy-two women were included. Forty-three (63 %) patients were hormone receptor-positive. Sixty-four (89 %) completed the planned treatment, and 66 evaluable patients underwent surgery (92 %): a pCR was achieved in 16 of them (24, 95 % CI 15-36 %). pCR was significantly higher in tumors hormone receptor-negative, and in those with Angiotensin II type 1 receptor (AGTR1) protein overexpression. The overall clinical response rate was 86 % (95 % CI 76-93 %), including 42 complete responses. No unexpected toxicities or treatment-related deaths were observed. CONCLUSION: This regimen showed a remarkable clinical and pathological activity: the suggested relation between pCR and AGTR1 overexpression should be confirmed in larger trials (AU)
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Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/cirugía , Biomarcadores/análisisRESUMEN
PURPOSE: The primary aim of this trial was to assess the rate of pathologic complete responses (pCR) of doxorubicin/cyclophosphamide (AC) followed by bevacizumab/docetaxel (BT), as neoadjuvant therapy for breast cancer (BC). Furthermore, the association between biomarkers and the pCR was explored. METHODS: Patients with HER-negative operable stage II-III BC ≥ 2 cm were enrolled. Four cycles of AC (A 60 mg/m(2) and C 600 mg/m(2), every 3 weeks) followed by 4 cycles of BT (B 15 mg/kg and T 75 mg/m(2), every 3 weeks), were planned. A core-biopsy was performed for biological markers assessment. RESULTS: Seventy-two women were included. Forty-three (63 %) patients were hormone receptor-positive. Sixty-four (89 %) completed the planned treatment, and 66 evaluable patients underwent surgery (92 %): a pCR was achieved in 16 of them (24, 95 % CI 15-36 %). pCR was significantly higher in tumors hormone receptor-negative, and in those with Angiotensin II type 1 receptor (AGTR1) protein overexpression. The overall clinical response rate was 86 % (95 % CI 76-93 %), including 42 complete responses. No unexpected toxicities or treatment-related deaths were observed. CONCLUSION: This regimen showed a remarkable clinical and pathological activity: the suggested relation between pCR and AGTR1 overexpression should be confirmed in larger trials.
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Inhibidores de la Angiogénesis/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/tratamiento farmacológico , Carcinoma Lobular/tratamiento farmacológico , Receptor ErbB-2/metabolismo , Adulto , Anciano , Bevacizumab , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/secundario , Carcinoma Lobular/metabolismo , Carcinoma Lobular/secundario , Ciclofosfamida/administración & dosificación , Docetaxel , Doxorrubicina/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Metástasis Linfática , Persona de Mediana Edad , Terapia Neoadyuvante , Estadificación de Neoplasias , Cuidados Preoperatorios , Pronóstico , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Inducción de Remisión , Taxoides/administración & dosificaciónRESUMEN
BACKGROUND: Aromatase inhibitors are the preferred adjuvant endocrine therapy for the majority of postmenopausal women with hormone-responsive early breast cancer. Although generally more effective than tamoxifen, aromatase inhibitor therapy is associated with increased bone loss and fracture risk. PATIENTS AND METHODS: Postmenopausal women receiving adjuvant letrozole (2.5 mg/day for 5 years; N = 1065) were randomly assigned to immediate zoledronic acid (zoledronate) 4 mg every 6 months for 5 years, or delayed zoledronate (initiated for fracture or on-study bone mineral density [BMD] decrease). The primary end point was the change in lumbar spine BMD at 12 months. Lumbar spine and total hip BMD at subsequent follow-up, disease-free survival (DFS), and overall survival were assessed as secondary end points. RESULTS: At 60 months (final analysis), the mean change in lumbar spine BMD was +4.3% with immediate zoledronate and -5.4% with delayed intervention (P < 0.0001). Immediate zoledronate reduced the risk of DFS events by 34% (hazard ratio [HR] = 0.66; P = 0.0375) with fewer local (0.9% versus 2.3%) and distant (5.5% versus 7.7%) recurrences versus delayed zoledronate. In the delayed group, delayed initiation of zoledronate substantially improved DFS versus no zoledronate (HR = 0.46; P = 0.0334). CONCLUSIONS: Immediate zoledronate in postmenopausal women receiving letrozole preserved BMD and is associated with improved DFS compared with letrozole alone. Clinical Trials Registration No NCT00171340.
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Antineoplásicos/uso terapéutico , Conservadores de la Densidad Ósea/uso terapéutico , Densidad Ósea/efectos de los fármacos , Neoplasias de la Mama/tratamiento farmacológico , Difosfonatos/uso terapéutico , Imidazoles/uso terapéutico , Nitrilos/uso terapéutico , Triazoles/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Inhibidores de la Aromatasa/efectos adversos , Inhibidores de la Aromatasa/uso terapéutico , Conservadores de la Densidad Ósea/efectos adversos , Neoplasias de la Mama/fisiopatología , Quimioterapia Adyuvante , Difosfonatos/efectos adversos , Supervivencia sin Enfermedad , Esquema de Medicación , Femenino , Humanos , Imidazoles/efectos adversos , Letrozol , Vértebras Lumbares/efectos de los fármacos , Vértebras Lumbares/metabolismo , Persona de Mediana Edad , Nitrilos/efectos adversos , Posmenopausia , Triazoles/efectos adversos , Ácido ZoledrónicoRESUMEN
BACKGROUND: Bevacizumab is a monoclonal antibody against vascular endothelial growth factor with the ability to increase progression-free survival in metastatic breast cancer (MBC). A systematic review and meta-analysis was conducted to determine the risk of the most clinically relevant adverse outcomes associated with the use of bevacizumab in the treatment of breast cancer. PATIENTS AND METHODS: We included phase III clinical trials that used bevacizumab alone or in combination with chemotherapy as for MBC or locally recurrent. Statistical analyses were conducted to calculate summary odds ratio (OR) of the eight most relevant adverse outcomes related with bevacizumab. RESULTS: Five clinical trials were included in the meta-analysis. Summary odds ratios obtained showed a statistically significant bevacizumab-associated increased risk in four of the adverse outcomes studied: proteinuria (OR = 27.68), hypertension (OR = 12.76), left ventricular dysfunction (LVD) (OR = 2.25), and hemorrhagic events (OR = 4.07). No statistically significant differences were found for gastrointestinal (GI) perforation, vascular events, fatal events, or febrile neutropenia. CONCLUSIONS: Bevacizumab did increase the risk of LVD and hemorrhagic events. The addition of bevacizumab to chemotherapy in patients with metastatic breast cancer was not associated with a significant increase in grade ≥ 3 arterial or venous thromboembolic events, GI perforation, or fatal events.
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Anticuerpos Monoclonales Humanizados/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Carcinoma/tratamiento farmacológico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Algoritmos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Bevacizumab , Neoplasias de la Mama/epidemiología , Carcinoma/epidemiología , Ensayos Clínicos Fase III como Asunto/estadística & datos numéricos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiología , Femenino , Humanos , Factores de RiesgoRESUMEN
BACKGROUND: The purpose of this study was (a) to evaluate the association between cigarette smoking and the prevalence of distal colorectal polyps and adenocarcinoma and (b) to analyse genetic alterations representing different molecular pathways of the colorectal carcinogenesis. METHODS: A total of 623 asymptomatic male (mean age: 53 years; 50-65) car factory workers were included. Information on smoking habits and other lifestyle factors were collected followed by a 60 cm colonoscopy. APC and KRAS mutations and microsatellite status were determined in colorectal lesions (colorectal carcinoma (CRC), hyperplastic (HP) and adenomatous polyps (AP)). Data were analysed using unconditional multiple logistic regression models. RESULTS: Smokers had a higher prevalence of AP (OR 2.1; 95% CI 1.2-3.6; p<0.05) and HP (OR 5.4; 95% CI 2.6- 11.1; p<0.05). No differences in CRC were observed. There was a dose-response relationship with the number of cigarettes smoked. The risk of developing AP or HP decreased after smoking cessation, even among heavy smokers (≥20 packs/year). KRAS mutations were more prevalent among smokers AP (OR 5.6; 95% CI 1.6-20.4; p=0.007). There was a trend of positive association with APC mutations (OR 3.5; 95% CI 0.9-4.4; p=0.096). APC and KRAS mutations were found in 36% and 61% of the HP of smokers, but were absent in non-smokers (p=0.89 and 0.78, respectively). There were no differences in MSI between smokers and non-smokers. CONCLUSIONS: Cigarette smoking is associated with a higher risk of developing both HP and AP and a higher prevalence of mutations in APC and KRAS (AU)