RESUMEN
BACKGROUND: The PENELOPE-B study demonstrated that the addition of 1-year post-neoadjuvant palbociclib to endocrine therapy (ET) in patients with high-risk early breast cancer (BC) did not improve invasive disease-free survival (iDFS) compared to placebo. Here, we report results for premenopausal women. PATIENTS AND METHODS: Patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative BC at high risk of relapse [defined as no pathological complete response after neoadjuvant chemotherapy and a clinical, pathological stage, estrogen receptor, grading (CPS-EG) score ≥3 or 2/ypN+] were randomized to receive 13 cycles of palbociclib or placebo + standard ET. Ovarian function (OF) was evaluated by centrally assessed estradiol, follicle-stimulating hormone and anti-Müllerian hormone serum levels. RESULTS: Overall, 616 of 1250 randomized patients were premenopausal; of these, 30.0% were <40 years of age, 47.4% had four or more metastatic lymph nodes, and 58.2% had a CPS-EG score ≥3. 66.1% of patients were treated with tamoxifen alone, and 32.9% received ovarian function suppression (OFS) in addition to either tamoxifen or aromatase inhibitor (AI). After a median follow-up of 42.8 months (97.2% completeness) no difference in iDFS between palbociclib and placebo was observed [hazard ratio = 0.95, 95% confidence interval (CI) 0.69-1.30, P = 0.737]. The estimated 3-year iDFS rate was marginally higher in the palbociclib arm (80.6% versus 78.3%). Three year iDFS was higher in patients receiving AI than tamoxifen plus OFS or tamoxifen alone (86.0% versus 78.6% versus 78.0%). Patients receiving tamoxifen plus OFS showed a favorable iDFS with palbociclib (83.0% versus 74.1%, hazard ratio = 0.52, 95% CI 0.27-1.02, P = 0.057). Hematologic adverse events were more frequent with palbociclib (76.1% versus 1.9% grade 3-4, P < 0.001). Palbociclib seems not to negatively impact the OF throughout the treatment period. CONCLUSIONS: In premenopausal women, who received tamoxifen plus OFS as ET, the addition of palbociclib to ET results in a favorable iDFS. The safety profile seems favorable and in contrast to chemotherapy palbociclib does not impact OF throughout the treatment period.
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Neoplasias de la Mama , Terapia Neoadyuvante , Piperazinas , Premenopausia , Piridinas , Receptor ErbB-2 , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Piperazinas/farmacología , Piperazinas/uso terapéutico , Piridinas/farmacología , Piridinas/uso terapéutico , Adulto , Terapia Neoadyuvante/métodos , Receptor ErbB-2/metabolismo , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Recurrencia Local de Neoplasia , Receptores de Estrógenos/metabolismo , Supervivencia sin EnfermedadRESUMEN
BACKGROUND: HER2 mutations are targetable alterations in patients with hormone receptor-positive (HR+) metastatic breast cancer (MBC). In the SUMMIT basket study, patients with HER2-mutant MBC received neratinib monotherapy, neratinib + fulvestrant, or neratinib + fulvestrant + trastuzumab (N + F + T). We report results from 71 patients with HR+, HER2-mutant MBC, including 21 (seven in each arm) from a randomized substudy of fulvestrant versus fulvestrant + trastuzumab (F + T) versus N + F + T. PATIENTS AND METHODS: Patients with HR+ HER2-negative MBC with activating HER2 mutation(s) and prior cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) therapy received N + F + T (oral neratinib 240 mg/day with loperamide prophylaxis, intramuscular fulvestrant 500 mg on days 1, 15, and 29 of cycle 1 then q4w, intravenous trastuzumab 8 mg/kg then 6 mg/kg q3w) or F + T or fulvestrant alone. Those whose disease progressed on F + T or fulvestrant could cross-over to N + F + T. Efficacy endpoints included investigator-assessed objective response rate (ORR), clinical benefit rate (RECIST v1.1), duration of response, and progression-free survival (PFS). Plasma and/or formalin-fixed paraffin-embedded tissue samples were collected at baseline; plasma was collected during and at end of treatment. Extracted DNA was analyzed by next-generation sequencing. RESULTS: ORR for 57 N + F + T-treated patients was 39% [95% confidence interval (CI) 26% to 52%); median PFS was 8.3 months (95% CI 6.0-15.1 months). No responses occurred in fulvestrant- or F + T-treated patients; responses in patients crossing over to N + F + T supported the requirement for neratinib in the triplet. Responses were observed in patients with ductal and lobular histology, 1 or ≥1 HER2 mutations, and co-occurring HER3 mutations. Longitudinal circulating tumor DNA sequencing revealed acquisition of additional HER2 alterations, and mutations in genes including PIK3CA, enabling further precision targeting and possible re-response. CONCLUSIONS: The benefit of N + F + T for HR+ HER2-mutant MBC after progression on CDK4/6is is clinically meaningful and, based on this study, N + F + T has been included in the National Comprehensive Cancer Network treatment guidelines. SUMMIT has improved our understanding of the translational implications of targeting HER2 mutations with neratinib-based therapy.
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Neoplasias de la Mama , Femenino , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Fulvestrant , Receptor ErbB-2 , TrastuzumabRESUMEN
Acute pancreatitis (AP) and recurrent acute pancreatitis (RAP) are conditions, whose incidence is apparently on the rise. Despite the ever-increasing evidence regarding the management of AP in children and adults, therapeutic actions that could potentially affect having a poor prognosis in those patients, especially in the pediatric population, continue to be carried out. Therefore, the Asociación Mexicana de Gastroenterología convened a group of 24 expert pediatric gastroenterologists from different institutions and areas of Mexico, as well as 2 pediatric nutritionists and 2 specialists in pediatric surgery, to discuss different aspects of the epidemiology, diagnosis, and treatment of AP and RAP in the pediatric population. The aim of this document is to present the consensus results. Different AP topics were addressed by 6 working groups, each of which reviewed the information and formulated statements considered pertinent for each module, on themes involving recommendations and points of debate, concerning diagnostic or therapeutic approaches. All the statements were presented and discussed. They were then evaluated through a Delphi process, with electronic and anonymous voting, to determine the level of agreement on the statements. A total of 29 statements were formulated, all of which reached above 75% agreement in the first round of voting.
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Pancreatitis , Adulto , Humanos , Niño , Adolescente , Pancreatitis/diagnóstico , Pancreatitis/terapia , Consenso , Enfermedad Aguda , México/epidemiologíaRESUMEN
Precision oncology research is challenging outside the contexts of oncogenic addiction and/or targeted therapies. We previously showed that phosphoproteomics is a powerful approach to reveal patient subsets of interest characterized by the activity of a few kinases where the underlying genomics is complex. Here, we conduct a phosphoproteomic screening of samples from HER2-negative female breast cancer receiving neoadjuvant paclitaxel (N = 130), aiming to find candidate biomarkers of paclitaxel sensitivity. Filtering 11 candidate biomarkers through 2 independent patient sets (N = 218) allowed the identification of a subgroup of patients characterized by high levels of CDK4 and filamin-A who had a 90% chance of achieving a pCR in response to paclitaxel. Mechanistically, CDK4 regulates filamin-A transcription, which in turn forms a complex with tubulin and CLIP-170, which elicits increased binding of paclitaxel to microtubules, microtubule acetylation and stabilization, and mitotic catastrophe. Thus, phosphoproteomics allows the identification of explainable factors for predicting response to paclitaxel.
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Neoplasias de la Mama , Paclitaxel , Femenino , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Quinasa 4 Dependiente de la Ciclina , Genómica , Paclitaxel/farmacología , Medicina de PrecisiónRESUMEN
Infections of the central nervous system caused by atypical bacteria are becoming more common. Borrelia burgdorferi and Rickettsia conorii are microorganisms transmitted by ticks; infection with these bacteria result in a wide spectrum of manifestations on imaging. In areas where these tick-borne microorganisms are endemic, including Spain, these infections must be included in the differential diagnosis of patients with a variety of systemic and neurologic symptoms. The clinical presentation of these infections is nonspecific, and CT is normally the initial imaging technique, although MRI is more sensitive to early changes. On MRI, these infections can manifest as small lesions in the deep supratentorial white matter that are hyperintense on T2-weighted/FLAIR sequences. It is fundamental to know the imaging characteristics of the different atypical bacterial infections and their differential diagnoses. Good history taking combined with complementary tests (blood tests and CSF analysis) and the neuroimaging findings can help reach the right diagnosis and enable appropriate treatment, thereby preventing possible neurological sequelae.
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Infecciones Bacterianas , Borrelia burgdorferi , Garrapatas , Animales , Sistema Nervioso Central , Humanos , AnamnesisRESUMEN
PURPOSE: The aim of this study was to understand the perception of family physicians, pulmonologists, and allergists with respect to diagnostic tests performed on patients with chronic cough and treatments prescribed to patients with refractory or unexplained chronic cough. We also assessed how these health professionals perceived the effectiveness of these treatments. METHODS: An anonymous survey was distributed by the scientific societies SEPAR, SEAIC, SEMERGEN, semFYC, and SEMG. Respondents were asked how often they perform diagnostic tests and prescribe treatments (responses from 1 = never to 10 = always) and how they perceived the effectiveness of the drugs used (from 1 = not at all to 10 = very effective). The correlation between perceived effectiveness and frequency of prescription was analyzed. RESULTS: The respondents comprised 620 family physicians, 92 pulmonologists, and 62 allergists. The most frequently performed diagnostic tests were chest x-ray and, among pulmonologists and allergists, simple spirometry and bronchodilator tests. The most frequently prescribed drugs were bronchodilators (percentages scoring 8-10 for each specialty: 43.2%, 42.4%, and 56.5%; p = 0.127), inhaled corticosteroids (36.9%, 55.4%, and 54.8%; p < 0.001), and antitussives (family physicians, 33.4%). Regarding perceived effectiveness, only bronchodilators, inhaled or oral corticosteroids, and opioids obtained a median effectiveness score > 5 (between 6 and 7). Correlation coefficients (ρ2) suggested that approximately 45% of prescription was related to perceived effectiveness. CONCLUSION: Although chronic cough is a common problem, diagnosis and treatment differ among specialists. The perceived effectiveness of drugs is generally low.
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Asma , Tos , Tos/diagnóstico , Tos/tratamiento farmacológico , Humanos , Percepción , Pautas de la Práctica en Medicina , Neumólogos , Encuestas y CuestionariosRESUMEN
OBJECTIVE: To understand the perception of family doctors, pulmonologists and allergists about the current approach to chronic cough and its impact on patients' quality of life. MATERIAL AND METHODS: Cross-sectional and anonymous survey disseminated through the scientific societies SEAIC, SEMERGEN, semFYC, SEMG and SEPAR. The participants were 620 family doctors, 92 pulmonologists and 62 allergists. A descriptive analysis of the answers was conducted. Response percentages, medians and interquartile intervals were presented. The differences in the percentages between specialties were evaluated with the chi-square. RESULTS: Only half of the respondents chose a duration greater than 8 weeks as a criterion for diagnosing chronic cough, and less than half considered refractory/unexplained chronic cough a disease in itself. Family doctors perceived that chronic cough had less impact on patients than did pulmonologists or allergists. After a diagnosis of refractory/unexplained chronic cough, all 3specialties considered the most common approach to be to initiate treatment and to do the follow-up of the patient themselves. Most stated that they had no protocols for managing chronic cough, and more than 90% considered these to be necessary. CONCLUSIONS: The management of patients with chronic cough by family doctors, pulmonologists or allergists seems to be heterogeneous. There is a need for protocols that standardise diagnosis, referral and treatment criteria to optimise patients' management and reduce the impact of chronic cough.
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Alergólogos , Neumólogos , Tos/diagnóstico , Tos/terapia , Estudios Transversales , Humanos , Percepción , Calidad de Vida , Encuestas y CuestionariosRESUMEN
BACKGROUND: Palbociclib plus endocrine therapy (ET) is the standard treatment of hormone receptor-positive and human epidermal growth factor receptor 2-negative, metastatic breast cancer (MBC). However, its efficacy has not been compared with that of chemotherapy in a phase III trial. PATIENTS AND METHODS: PEARL is a multicentre, phase III randomised study in which patients with aromatase inhibitor (AI)-resistant MBC were included in two consecutive cohorts. In cohort 1, patients were randomised 1 : 1 to palbociclib plus exemestane or capecitabine. On discovering new evidence about estrogen receptor-1 (ESR1) mutations inducing resistance to AIs, the trial was amended to include cohort 2, in which patients were randomised 1 : 1 between palbociclib plus fulvestrant and capecitabine. The stratification criteria were disease site, prior sensitivity to ET, prior chemotherapy for MBC, and country of origin. Co-primary endpoints were progression-free survival (PFS) in cohort 2 and in wild-type ESR1 patients (cohort 1 + cohort 2). ESR1 hotspot mutations were analysed in baseline circulating tumour DNA. RESULTS: From March 2014 to July 2018, 296 and 305 patients were included in cohort 1 and cohort 2, respectively. Palbociclib plus ET was not superior to capecitabine in both cohort 2 [median PFS: 7.5 versus 10.0 months; adjusted hazard ratio (aHR): 1.13; 95% confidence interval (CI): 0.85-1.50] and wild-type ESR1 patients (median PFS: 8.0 versus 10.6 months; aHR: 1.11; 95% CI: 0.87-1.41). The most frequent grade 3-4 toxicities with palbociclib plus exemestane, palbociclib plus fulvestrant and capecitabine, respectively, were neutropenia (57.4%, 55.7% and 5.5%), hand/foot syndrome (0%, 0% and 23.5%), and diarrhoea (1.3%, 1.3% and 7.6%). Palbociclib plus ET offered better quality of life (aHR for time to deterioration of global health status: 0.67; 95% CI: 0.53-0.85). CONCLUSIONS: There was no statistical superiority of palbociclib plus ET over capecitabine with respect to PFS in MBC patients resistant to AIs. Palbociclib plus ET showed a better safety profile and improved quality of life.
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Inhibidores de la Aromatasa , Neoplasias de la Mama , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Inhibidores de la Aromatasa/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Capecitabina/uso terapéutico , Familia de Proteínas EGF/uso terapéutico , Humanos , Piperazinas , Piridinas , Calidad de Vida , Receptor ErbB-2/genética , Receptores de EstrógenosRESUMEN
BACKGROUND: Neratinib is an irreversible pan-HER tyrosine kinase inhibitor approved for extended adjuvant treatment in early-stage HER2-positive breast cancer based on the phase III ExteNET study. In that trial, in which no antidiarrheal prophylaxis was mandated, grade 3 diarrhea was observed in 40% of patients and 17% discontinued due to diarrhea. The international, open-label, sequential-cohort, phase II CONTROL study is investigating several strategies to improve tolerability. PATIENTS AND METHODS: Patients who completed trastuzumab-based adjuvant therapy received neratinib 240 mg/day for 1 year plus loperamide prophylaxis (days 1-28 or 1-56). Sequential cohorts evaluated additional budesonide or colestipol prophylaxis (days 1-28) and neratinib dose escalation (DE; ongoing). The primary end point was the incidence of grade ≥3 diarrhea. RESULTS: Final data for loperamide (L; n = 137), budesonide + loperamide (BL; n = 64), colestipol + loperamide (CL; n = 136), and colestipol + as-needed loperamide (CL-PRN; n = 104) cohorts, and interim data for DE (n = 60; completed ≥six cycles or discontinued; median duration 11 months) are available. No grade 4 diarrhea was observed. Grade 3 diarrhea rates were lower than ExteNET in all cohorts and lowest in DE (L 31%, BL 28%, CL 21%, CL-PRN 32%, DE 15%). Median number of grade 3 diarrhea episodes was one; median duration per grade 3 episode was 1.0-2.0 days across cohorts. Most grade 3 diarrhea and diarrhea-related discontinuations occurred in month 1. Diarrhea-related discontinuations were lowest in DE (L 20%, BL 8%, CL 4%, CL-PRN 8%, DE 3%). Decreases in health-related quality of life did not cross the clinically important threshold. CONCLUSIONS: Neratinib tolerability was improved with preemptive prophylaxis or DE, which reduced the rate, severity, and duration of neratinib-associated grade ≥3 diarrhea compared with ExteNET. Lower diarrhea-related treatment discontinuations in multiple cohorts indicate that proactive management can allow patients to stay on neratinib for the recommended time period. CLINICALTRIALS.GOV: NCT02400476.
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Neoplasias de la Mama , Quinolinas , Receptor ErbB-2 , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Humanos , Calidad de Vida , Quinolinas/uso terapéutico , Receptor ErbB-2/genética , Trastuzumab/uso terapéuticoRESUMEN
Asthma is the most prevalent respiratory disease worldwide and it can affect people of all ages and is potentially fatal. Today, maintenance treatments are available that are effective in most patients, yet a significant proportion have poorly controlled disease, despite the resources on offer. This document, endorsed by members of the Spanish medical societies involved in the treatment of asthma, is intended to draw the attention of society and professionals to this problem in Spain. It focuses on the clinical, diagnostic and therapeutic aspects of asthma, and proposes some actions for improvement as regards patients and healthcare professionals which, in view of the current results arising from inadequate asthma control, might be beneficial to improve outcomes for both patients and public health.
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Asma , Salud Global , Enfermedad Crónica , Humanos , Inflamación , Sociedades Científicas , EspañaRESUMEN
PURPOSE: Hormone receptor (HR)-positive, Human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) requires a therapeutic approach that takes into account multiple factors, with treatment being based on anti-estrogen hormone therapy (HT). As consensus documents are valuable tools that assist in the decision-making process for establishing clinical strategies and optimize the delivery of health services, this consensus document has been created with the aim of developing recommendations on cretiera for hormone sensitivity and resistance in HER2-negative luminal MBC and facilitating clinical decision-making. METHODS: This consensus document was generated using a modification of the RAND/UCLA methodology, which included the definition of the project and identification of issues of interest, a non-exhaustive systematic review of the literature, an analysis and synthesis of the scientific evidence, preparation of recommendations, and external evaluation with a panel of 64 medical oncologists specializing in breast cancer. RESULTS: A Spanish panel of experts reached consensus on 32 of the 32 recommendations/conclusions presented in the first round and were accepted with an approval rate of 100% about definition of metastatic disease not susceptible to local curative treatment, definition of hormone sensitivity and hormone resistance in metastatic luminal disease and therapeutic decision-making. CONCLUSION: We have developed a consensus document with recommendations on the treatment of patients with HER2-negative luminal MBC that will help to improve therapeutic benefits.
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Antineoplásicos Hormonales/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Toma de Decisiones Clínicas , Consenso , Receptor ErbB-2 , Anciano , Biomarcadores de Tumor/sangre , Biopsia , Mama/patología , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Resistencia a Antineoplásicos , Femenino , Expresión Génica , Humanos , Inmunohistoquímica , Antígeno Ki-67/análisis , Menopausia/metabolismo , Persona de Mediana Edad , Terapia Molecular Dirigida , Recurrencia Local de Neoplasia/metabolismo , Neoplasias Hormono-Dependientes/diagnóstico , Ovario/efectos de los fármacos , Guías de Práctica Clínica como Asunto , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismoRESUMEN
This document gathers the opinion of a multidisciplinary forum of experts on different aspects of the diagnosis and treatment of Clostridioides difficile infection (CDI) in Spain. It has been structured around a series of questions that the attendees considered relevant and in which a consensus opinion was reached. The main messages were as follows: CDI should be suspected in patients older than 2 years of age in the presence of diarrhea, paralytic ileus and unexplained leukocytosis, even in the absence of classical risk factors. With a few exceptions, a single stool sample is sufficient for diagnosis, which can be sent to the laboratory with or without transportation media for enteropathogenic bacteria. In the absence of diarrhoea, rectal swabs may be valid. The microbiology laboratory should include C. difficile among the pathogens routinely searched in patients with diarrhoea. Laboratory tests in different order and sequence schemes include GDH detection, presence of toxins, molecular tests and toxigenic culture. Immediate determination of sensitivity to drugs such as vancomycin, metronidazole or fidaxomycin is not required. The evolution of toxin persistence is not a suitable test for follow up. Laboratory diagnosis of CDI should be rapid and results reported and interpreted to clinicians immediately. In addition to the basic support of all diarrheic episodes, CDI treatment requires the suppression of antiperistaltic agents, proton pump inhibitors and antibiotics, where possible. Oral vancomycin and fidaxomycin are the antibacterials of choice in treatment, intravenous metronidazole being restricted for patients in whom the presence of the above drugs in the intestinal lumen cannot be assured. Fecal material transplantation is the treatment of choice for patients with multiple recurrences but uncertainties persist regarding its standardization and safety. Bezlotoxumab is a monoclonal antibody to C. difficile toxin B that should be administered to patients at high risk of recurrence. Surgery is becoming less and less necessary and prevention with vaccines is under research. Probiotics have so far not been shown to be therapeutically or preventively effective. The therapeutic strategy should be based, rather than on the number of episodes, on the severity of the episodes and on their potential to recur. Some data point to the efficacy of oral vancomycin prophylaxis in patients who reccur CDI when systemic antibiotics are required again.
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Clostridioides difficile , Infecciones por Clostridium/diagnóstico , Infecciones por Clostridium/tratamiento farmacológico , Antibacterianos/uso terapéutico , Clostridioides difficile/aislamiento & purificación , Continuidad de la Atención al Paciente , Análisis Costo-Beneficio , Diarrea/microbiología , Heces/microbiología , Femenino , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Probióticos/uso terapéutico , Prevención Secundaria , Sociedades Médicas/normas , España , Manejo de Especímenes/métodosRESUMEN
INTRODUCTION: The aim of this study is to evaluate the cost-effectiveness and impact of gene-expression assays (GEAs) on treatment decisions in a real-world setting of early-stage breast cancer (ESBC) patients. METHODS: This is a regional, prospective study promoted by the Council Health Authorities in Madrid. Enrolment was offered to women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative, node-negative or micrometastatic, stage I or II breast cancer from 21 hospitals in Madrid. Treatment recommendations were recorded before and after knowledge of tests results. An economic model compared the cost-effectiveness of treatment, guided by GEAs or by common prognostic factors. RESULTS: 907 tests (440 Oncotype DX® and 467 MammaPrint®) were performed between February 2012 and November 2014. Treatment recommendation changed in 42.6% of patients. The shift was predominantly from chemohormonal (CHT) to hormonal therapy (HT) alone, in 30.5% of patients. GEAs increased patients' confidence in treatment decision making. Tumor grade, progesterone receptor positivity and Ki67 expression were associated with the likelihood of change from CHT to HT (P < 0.001) and from HT to CHT (P < 0.001). Compared with current clinical practice genomic testing increased quality-adjusted life years by 0.00787 per patient and was cost-saving from a national health care system (by 13.867 per patient) and from a societal perspective (by 32.678 per patient). CONCLUSION: Using GEAs to guide adjuvant therapy in ESBC is cost-effective in Spain and has a significant impact on treatment decisions.
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Neoplasias de la Mama/tratamiento farmacológico , Perfilación de la Expresión Génica/economía , Sistema de Registros , Adolescente , Adulto , Anciano , Biomarcadores de Tumor/genética , Neoplasias de la Mama/economía , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Quimioterapia Adyuvante , Toma de Decisiones Clínicas , Análisis Costo-Beneficio , Femenino , Perfilación de la Expresión Génica/métodos , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Años de Vida Ajustados por Calidad de Vida , España/epidemiología , Adulto JovenRESUMEN
PURPOSE: To evaluate the efficacy and safety of lapatinib (L) and trastuzumab (T) combination in HER2-positive metastatic breast cancer (MBC) patients previously treated with T and/or L. MATERIALS AND METHODS: We conducted a retrospective, post-authorized, multicenter study including patients with HER2-positive MBC or locally advanced breast cancer (ABC) treated with the combination of L-T. Concomitant endocrine therapy, as well as brain metastasis and/or prior exposure to L, were allowed. RESULTS: One hundred and fifteen patients from 14 institutions were included. The median age was 59.8 years. The median number of prior T regimens in the advanced setting was 3 and 73 patients had received a prior L regimen. The clinical benefit rate (CBR) was 34.8% (95% CI 26.1-43.5). Among other efficacy endpoints, the overall response rate was 21.7%, and median progression-free survival (PFS) and overall survival were 3.9 and 21.6 months, respectively. Heavily pretreated and ≥ 3 metastatic organ patients showed lower CBR and PFS than patients with a low number of previous regimens and < 3 metastatic organs. Moreover, CBR did not significantly change in L-pretreated compared with L-naïve patients (31.5% versus 40.5% for L-pretreated versus L-naïve). Grade 3/4 adverse events were reported in 19 patients (16.5%). CONCLUSION: The combination of L-T is an effective and well-tolerated regimen in heavily pretreated patients and remains active among patients progressing on prior L-based therapy. Our study suggests that the L-T regimen is a safe and active chemotherapy-free option for MBC patients previously treated with T and/or L.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Lapatinib/uso terapéutico , Receptor ErbB-2/metabolismo , Trastuzumab/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/patología , Femenino , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Inhibidores de Proteínas Quinasas/uso terapéutico , Receptor ErbB-2/antagonistas & inhibidores , Estudios Retrospectivos , España , Resultado del TratamientoRESUMEN
The interaction forces between identical resonant molecules or nanoparticles, optically induced by a quasimonochromatic isotropic random light field, are theoretically analyzed. In general, the interaction force exhibits a far-field oscillatory behavior at separation distances larger than the light wavelength. However, we show that the oscillations disappear when the frequency of the random field is tuned to an absorption Fröhlich resonance, at which the real part of the particle's electric polarizability is zero. At the resonant condition, the interaction forces follow a long-range gravitylike inverse square distance law which holds for both near- and far-field separation distances.
RESUMEN
The aim was to evaluate the associations of environmental phenol and paraben concentrations with the oxidative microenvironment in adipose tissue. This study was conducted in a subsample (nâ¯=â¯144) of the GraMo cohort (Southern Spain). Concentrations of 9 phenols and 7 parabens, and levels of oxidative stress biomarkers were quantified in adipose tissue. Associations were estimated using multivariable linear regression analyses adjusted for potential confounders. Benzophenone-3 (BP-3) concentration was borderline associated with enhanced glutathione peroxidase (GPx) activity [exp(ß)â¯=â¯1.20, pâ¯=â¯0.060] and decreased levels of reduced glutathione (GSH) [exp(ß)â¯=â¯0.55, pâ¯=â¯0.070]. Concentrations of bisphenol A (BPA) and methylparaben (MeP) were associated to lower glutathione reductase (GRd) activity [exp(ß)â¯=â¯0.83, exp(ß)â¯=â¯0.72, respectively], and BPA was borderline associated to increased levels of oxidized glutathione (GSSG) [exp(ß)â¯=â¯1.73, p-valueâ¯=â¯0.062]. MeP was inversely associated to both hemeoxygenase-1 (HO-1) and superoxide dismustase (SOD) activity, as well as to the levels of thiobarbituric acid reactive substances (TBARS) [0.75â¯<â¯exp(ß)â¯<â¯0.79]. Our results suggest that some specific non-persistent pollutants may be associated with a disruption of the activity of relevant antioxidant enzymes, in addition to the depletion of the glutathione stock. They might act as a tissue-specific source of free radicals, contributing to the oxidative microenvironment in the adipose tissue.
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Tejido Adiposo/metabolismo , Contaminantes Ambientales/metabolismo , Fenoles/metabolismo , Adulto , Antioxidantes/metabolismo , Compuestos de Bencidrilo/metabolismo , Benzofenonas/metabolismo , Biomarcadores/metabolismo , Estudios de Cohortes , Femenino , Radicales Libres/metabolismo , Glutatión/metabolismo , Glutatión Peroxidasa , Humanos , Masculino , Persona de Mediana Edad , Oxidación-Reducción , Estrés Oxidativo , Parabenos/metabolismo , España , Sustancias Reactivas al Ácido TiobarbitúricoRESUMEN
The present review of noncaloric sweeteners (NCSs) by the Asociación Mexicana de Gastroenterología was carried out to analyze and answer some of the most frequent questions and concerns about NCS consumption in patients with gastrointestinal disorders, through a thorough review of the medical literature. A group of gastroenterologists and experts on nutrition, toxicology, microbiology, and endocrinology reviewed and analyzed the published literature on the topic. The working group formulated conclusions, based on the scientific evidence published, to give an opinion with respect to NCS ingestion. Current evidence does not confirm the carcinogenic potential of NCSs. However, the studies analyzed showed that saccharin could have a proinflammatory effect and that polyols can cause gastrointestinal symptoms and manifestations, depending on the dose and type of compound. The ingestion of xylitol, erythritol, sucralose, aspartame, acesulfame K, and saccharin could increase the secretion of the gastrointestinal hormones that regulate intestinal motility, and stevia and its derivatives could have a favorable effect on the percentage of liver fat. Caution should be taken in recommending aspartame consumption in patients with chronic liver disease because it reduces the ratio of branched-chain amino acids to aromatic amino acids. In addition, NCS ingestion could modify the composition of the intestinal microbiota, having an effect on gastrointestinal symptoms and manifestations. It is important to continue conducting causality studies on humans to be able to establish recommendations on NSC consumption.