RESUMO
Immune checkpoint inhibitors are used in the treatment of different types of tumors including melanoma and non-small cell lung carcinoma. The use of these inhibitors is associated with a broad spectrum of immune-related adverse effects. Here we report a case of a patient admitted to the intensive care unit with multiple organ failure due to catastrophic antiphospholipid syndrome following treatment with pembrolizumab, an immune checkpoint inhibitor, because of metastatic melanoma. The presented patient had multiple organ failure of lung, gastro-intestinal, renal, and the liver. Vascular thrombosis was confirmed by both imaging (pulmonary embolism on computed tomography-thorax) and histopathological examination of the intestines. In combination with the presence of IgA anti-cardiolipin antibodies and initially IgM anti-cardiolipin antibodies, catastrophic antiphospholipid syndrome was suspected. Despite treatment with plasmapheresis and corticosteroids, the patient died due to multiple organ failure. Catastrophic antiphospholipid syndrome is difficult to recognize and has high mortality rates despite supportive treatment. In this case report, discussion is provided regarding the possible immunological mechanism behind catastrophic antiphospholipid syndrome during or after treatment with immune checkpoint inhibitors. It is important to realize that in modern intensive care unit, more patients with immune-related adverse effects of the treatment with immune checkpoint inhibitors will be admitted, because of an increase in the number of patients treated with these checkpoint inhibitors. When these patients are admitted on the intensive care unit, multi-disciplinary consultation is important because of the difficulty of early recognition and optimal treatment of these possible lethal side effects.
RESUMO
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disease characterized by a deregulated complement system, chronic Coombs-negative, intravascular hemolysis, and a variable clinical course with substantial risk to develop thromboembolic events. We analyzed diagnostic and prognostic parameters as well as clinical endpoints in 59 adult patients suffering from PNH in 5 hematology centers in Austria (observation period: 1978-2015). Median follow-up time was 5.6 years. The median clone size at diagnosis amounted to 55% and was higher in patients with classical PNH (81%) compared to patients with PNH associated with aplastic anemia (AA) or myelodysplastic syndromes (MDS) (50%). The clone size also correlated with lactate dehydrogenase (LDH) levels. In one patient, anemia improved spontaneously and disappeared with complete normalization of LDH after 16 years. Seventeen patients received therapy with eculizumab. The rate of thromboembolic events was higher in the pre-eculizumab era compared with eculizumab-treated patients but did not correlate with the presence of age-related clonal hematopoiesis or any other clinical or laboratory parameters. Peripheral blood colony-forming progenitor cell counts were lower in PNH patients compared with healthy controls. Only two patients with classical PNH developed MDS. Overall, 7/59 patients died after 0.5-32 years. Causes of death were acute pulmonary hypertension, Budd-Chiari syndrome, and septicemia. Overall survival (OS) was mainly influenced by age and was similar to OS measured in an age-matched healthy Austrian control cohort. Together, compared with previous times, the clinical course and OS in PNH are favorable, which may be due to better diagnosis, early recognition, and eculizumab therapy.
Assuntos
Hemoglobinúria Paroxística/epidemiologia , Injúria Renal Aguda/sangue , Injúria Renal Aguda/etiologia , Adulto , Anemia Aplástica/epidemiologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Áustria/epidemiologia , Medula Óssea/patologia , Causas de Morte , Células Clonais/patologia , Ensaio de Unidades Formadoras de Colônias , Terapia Combinada , Inativadores do Complemento/uso terapêutico , Creatinina/sangue , Progressão da Doença , Feminino , Seguimentos , Hematopoese , Transplante de Células-Tronco Hematopoéticas , Hemoglobinúria Paroxística/complicações , Hemoglobinúria Paroxística/tratamento farmacológico , Hemoglobinúria Paroxística/terapia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/epidemiologia , Gravidez , Complicações Hematológicas na Gravidez/epidemiologia , Prognóstico , Tromboembolia/etiologiaRESUMO
The Gram-negative bacterium, Salmonella Typhimurium (S. Typhimurium) is a food borne pathogen responsible for numerous hospitalisations and deaths all over the world. Conventional detection methods for pathogens are time consuming and labour-intensive. Hence, there is considerable interest in faster and simpler detection methods. Polypyrrole-based polymers, due to their intrinsic chemical and electrical properties, have been demonstrated to be valuable candidates for the fabrication of chemo/biosensors and functional surfaces. Similarly aptamers have been shown to be good alternatives to antibodies in the development of affinity biosensors. In this study, we report on the combination of poly [pyrrole-co-3-carboxyl-pyrrole] copolymer and aptamer for the development of a label-less electrochemical biosensor suitable for the detection of S. Typhimurium. Impedimetric measurements were facilitated by the effect of the aptamer/target interaction on the intrinsic conjugation of the poly [pyrrole-co-3-carboxyl-pyrrole] copolymer and subsequently on its electrical properties. The aptasensor detected S. Typhimurium in the concentration range 10(2)-10(8) CFU mL(-1) with high selectivity over other model pathogens and with a limit of quantification (LOQ) of 100 CFU mL(-1) and a limit of detection (LOD) of 3 CFU mL(-1). The suitability of the aptasensor for real sample detection was demonstrated via recovery studies performed in spiked apple juice samples. We envisage this to be a viable approach for the inexpensive and rapid detection of pathogens in food, and possibly in other environmental samples.
Assuntos
Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais , Salmonella typhimurium/isolamento & purificação , Microbiologia de Alimentos , Limite de Detecção , Polímeros/química , Pirróis/química , Salmonella typhimurium/patogenicidadeRESUMO
Polypyrrole coated gold wires were subjected to consecutive square current waves in LiClO4 aqueous solutions using the same constant anodic and cathodic charge. Parallel in situ diameter variations were followed using a laser scan micrometer. The procedure was repeated by changing one experimental variable every time: applied current, electrolyte concentration or working temperature to perform electrochemodynamical characterization of the system. On average, the diameter follows a linear variation of the consumed charge, as expected for any faradaic system, although a high dispersion was attained in the data. Such deviations were attributed to the presence of irreversible hydrogen evolution at the gold/polypyrrole interface at cathodic potentials more than 0.0 V vs. Ag/AgCl, detected and quantified from separated coulovoltammetric responses. Despite this parallel hydrogen evolution the consumed energy during reactions is a robust sensor of the working conditions. In conclusion a gold support, the metal most used for technological applications of conducting polymers, should be avoided when a device is driven by current flow in the presence of aqueous solutions, water contamination or moisture: a fraction of the charge will be consumed by hydrogen generation with possible degradation of the device.
RESUMO
Adenoviruses are excellent immunotherapeutic agents with a unique ability to prime and boost immune responses. Recombinant adenoviruses cause immunogenic cancer cell death and subsequent release of tumor antigens for antigen presenting cells, resulting in the priming of potent tumor-specific immunity. This effect may be further enhanced by immune-stimulating transgenes expressed by the virus. We report a case of a 38-year-old female with Stage 3 metastatic micropapillary serous carcinoma of the ovary. She was treated in a Phase I study with a granulocyte-macrophage colony stimulating factor (GMCSF)-expressing oncolytic adenovirus, Ad5/3-D24-GMCSF (ONCOS-102). The treatment resulted in progressive infiltration of CD8+ lymphocytes into the tumor and concomitant systemic induction of several tumor-specific CD8+ T-cell populations. The patient was alive at the latest follow up more than 20 months after initiation of the study.
RESUMO
BACKGROUND: Endoscopy is an important part of modern medical diagnostics and therapy. The invasive procedures are however associated with a risk to transmit infections. Against this background the KRINKO has published the "Hygienic requirements for the reprocessing of flexible endoscopes and endoscopic accessories" in 2002 and has updated these recommendations in 2012. In 2003 and 2013 all gastroenterological facilities in Frankfurt am Main using flexible endoscopes were monitored for compliance with the recommendations. METHODS: The inspections were performed after prior notice by a staff member of the health authority using a checklist which had been developed on the basis of the current KRINKO recommendations. RESULTS: In both years all institutions performing endoscopic procedures were visited: 2003 15 hospitals and 23 practices; 2013 14 clinics and 10 practices. In 2013 (data for 2003 in brackets) 100â% (93â%) of the hospitals and 60â% (22â%) of practices reprocessed their endoscopes by automated methods. The appropriate reprocessing and filling of water bottles for rinsing the scope channels with sterile water and the sterilisation of accessories were satisfactorily performed in 2003 and 2013 by all hospitals. However in 2013 only 90â% (2003: 74â%) of the practices correctly reprocessed water bottles and 80â% (52â%) used sterile water for filling the bottle. In 2013 100â% (2003: 57â%) of the practices correctly sterilised accessory instruments, while 2 practices used disposable, i.âe., single-use materials. In 2013 all institutions performed microbiological tests according to KRINKO recommendations, while in 2003 all hospitals but only 43â% of the practices could present such tests. DISCUSSION: While the gastroenterological departments of Frankfurt hospitals already complied with the KRINKO recommendations in 2003, the inspection of several practices in 2003 had revealed considerable shortcomings in the implementation of these recommendations. Subsequently the practices have improved their hygiene management.
Assuntos
Endoscópios Gastrointestinais/microbiologia , Endoscópios Gastrointestinais/estatística & dados numéricos , Contaminação de Equipamentos/prevenção & controle , Contaminação de Equipamentos/estatística & dados numéricos , Fidelidade a Diretrizes/estatística & dados numéricos , Higiene/normas , Padrões de Prática Médica/estatística & dados numéricos , Endoscópios Gastrointestinais/normas , Endoscopia , Endoscopia Gastrointestinal , Gastroenterologia/normas , Alemanha , Guias de Prática Clínica como Assunto , Padrões de Prática Médica/normas , Avaliação de Processos em Cuidados de Saúde/métodos , EsterilizaçãoRESUMO
The study explored the interdependence of changes in oxygen uptake, quality of life and cancer-related side-effect fatigue during a 4-month exercise intervention. Participants were during adjuvant (curative) or palliative therapy and post-adjuvant therapy (finished within the previous 12 months). Aerobic exercise capacity (VO2 peak), quality of life and fatigue symptom (EORTC QLQ-C30) were obtained in 101 cancer patients (30-77 years). After initial examination, patients participated in supervised and/or home-based training interventions. Patients were re-examined after 16-20 weeks and stratified into 3 subgroups (terciles) with respect to the absolute change in VO2 peak. The ANCOVA, with significant covariate effect for pretest fatigue score (F(5,101) = 8.150, P < 0.001), indicated significant differences between groups in outcome measures (P < 0.001). Based on the absolute change of VO2 peak (1.9 ± 1.7; 1.8 ± 0.8; 5.7 ± 2.8 ml/kg/min) there were significant differences in the quality of life improvement (17.2 ± 15.1 vs. 4.8 ± 22.0 points, P < 0.05) and cancer-related fatigue reduction (-6.1 ± 30.7; -11.5 ± 20.9; -21.2 ± 21.4 points) between upper and lower tercile. The findings point towards a relationship of exercise capacity enhancement, quality of life improvement and fatigue symptom reduction during and shortly after cancer treatment.
Assuntos
Terapia por Exercício , Fadiga/reabilitação , Neoplasias/reabilitação , Qualidade de Vida , Adulto , Idoso , Quimioterapia Adjuvante , Terapia por Exercício/estatística & dados numéricos , Fadiga/etiologia , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/terapia , Cuidados Paliativos , Resultado do TratamentoAssuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/secundário , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/secundário , Inibidores de Proteínas Quinases/uso terapêutico , HumanosRESUMO
Diagnostic lymph node dissections can be defined as a form of oncological service surgery. These procedures aim at clarification of differential diagnoses of local or systemic lymph node pathologies or contribute to tumor staging. Procedure implementation can either involve incisional biopsy, selective lymph node extirpation or regional systematic lymph node dissection. Sentinel lymph node lymphadenectomy is a focused form of selective lymphadenectomy. Both surgeon and oncologist must have a preoperative consensus and mutual understanding about the detailed purpose of the procedure in the individual patient setting. Terminology conventions must be considered in communication. Potential reasons to extend surgery should be strategically reflected prior to surgery. Interventional techniques and minimally invasive forms of surgical lymph node dissection must be technically taken into account in order to reduce procedural morbidity. Clinically indicative scenarios, pathophysiological concepts and technical options of surgical lymph node dissection are described and discussed for various anatomical regions.
Assuntos
Excisão de Linfonodo/métodos , Neoplasias/cirurgia , Abdome/cirurgia , Comportamento Cooperativo , Humanos , Canal Inguinal/cirurgia , Comunicação Interdisciplinar , Linfonodos/patologia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Pescoço/cirurgia , Neoplasias/patologia , Complicações Pós-Operatórias/prevenção & controle , Biópsia de Linfonodo SentinelaRESUMO
The present study evaluated the validity of the six-minute walk test (6MWT) in cancer patients. 50 subjects (36 f, 14 m; 57.4±10.2 years; during (56%) or off (44%) cancer treatment) performed a 6MWT and a spiroergometry on a cycle ergo-meter (0+25 W, 3 min) to evaluate maximum exercise capacity (VO2peak). A subsample (n=30) completed a retest of the 6MWT within 2-7 days. Patients covered a distance of 594±81 m during 6MWT at an average intensity of 86.3±9.6% of HRmax and achieved a VO2peak of 21.2±4.86 ml · kg - 1 · min - 1 during cycle ergometry. The distance walked correlated significantly (p<0.001) with VO2peak (r=0.67) and perceived physical function (EORTC QLQ-C30 physical function subscale) (r=0.55). Concerning reliability the intraclass correlation coefficient was r=0.93 (95%CI: +0.86;+0.97; p<0.001) and the coefficient of variation 3%. During retest participants walked 3.1% (95%CI: +1.1; +5.2) farther and achieved a higher RPE (+1.0; 95%CI: +0.3;+1.8). Limits of agreement were between - 43.1 and 76.4 m. In cancer patients the 6MWT seems to be as valid and reliable as in healthy elderly, cardiac and pulmonary patients. Thus, it can be recommended for use in cancer patients.
Assuntos
Ciclismo/fisiologia , Teste de Esforço/métodos , Neoplasias/patologia , Caminhada/fisiologia , Adulto , Idoso , Tolerância ao Exercício/fisiologia , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/terapia , Oxigênio/metabolismo , Reprodutibilidade dos TestesRESUMO
BACKGROUND: This study was designed to compare cisplatin/docetaxel with oxaliplatin/docetaxel in patients with advanced and metastatic non-small lung cancer as a first-line treatment. METHODS: Patients were randomly assigned to receive either cisplatin 75 mg m(-2) and docetaxel 75 mg m(-2) every 3 weeks or oxaliplatin 85 mg m(-2) and docetaxel 50 mg m(-2) every 2 weeks. The primary end point was response rate, and secondary end points were toxicity, time to progression and overall survival. RESULTS: A total of 88 patients (median age: 65 (39-86) years; stage IV: 93%) were randomly assigned. Response rate (complete and partial response) was 47% (95% CI: 33-61%) in the cisplatin/docetaxel arm and 28% (95% CI: 17-43%) in the oxaliplatin/docetaxel arm (P=0.118). There was no significant difference in time to progression (6.3 vs 4.9 months, P=0.111) and median overall survival (11.6 vs 7.0 months, P=0.102) with cisplatin/docetaxel vs oxaliplatin/docetaxel, although slight trends favouring cisplatin were seen. Oxaliplatin/docetaxel was associated with significantly less (any grade) renal toxicity (56% vs 11%), any grade fatigue (81% vs 59%), complete alopecia (76% vs 27%), any grade leukopenia (84% vs 61%) and grade 3/4 leukopenia (44% vs 14%) and neutropenia (56% vs 27%). CONCLUSION: Oxaliplatin/docetaxel has activity in metastatic non-small cell lung cancer, but it seems to be inferior to cisplatin/docetaxel.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cisplatino/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Compostos Organoplatínicos/administração & dosagem , Taxoides/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Cisplatino/efeitos adversos , Docetaxel , Esquema de Medicação , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina , Taxoides/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: The aim of this exploratory subgroup analysis of the fluorouracil, oxaliplatin, docetaxel (FLOT)65+ trial was to determine tolerability and feasibility of perioperative chemotherapy in elderly, potentially operable esophagogastric cancer patients. METHODS: Patients aged ≥65 with locally advanced esophagogastric adenocarcinoma were randomized to perioperative chemotherapy consisting of four pre- and four postoperative cycles of infusional 5-FU, leucovorin, and oxaliplatin (FLO) without or with docetaxel 50 mg m(-)(2) (FLOT), every 2 weeks. RESULTS: Forty-four patients with a median age of 70 years were randomized and 43 patients started preoperative chemotherapy (FLO, 22; FLOT, 21). Thirty-eight (86.4%) patients completed four cycles of preoperative chemotherapy and 32 (74.4%) proceeded to surgery, with 67.4% R0 resections on intent-to-treat analysis (90.1% of the 32 patients who underwent resection). Median overall survival was not reached and median progression-free survival (PFS) was 17.3 months. Compared with the FLO group, the FLOT group showed a trend towards an improved median PFS (21.1 vs 12.0 months; P=0.09), however, associated with increased chemotherapy related toxicity. No perioperative mortality was observed. Postoperative morbidity was observed in 46.9% of patients (FLO, 35.3%; FLOT, 60%). CONCLUSION: Neoadjuvant FLO or FLOT may offer a reasonable chance of curative surgery in elderly patients with locally advanced resectable gastroesophageal cancer. However, the increase in side effects with the FLOT regimen and postoperative morbidity should be carefully considered when an intensive chemotherapy regimen is planned.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Idoso , Docetaxel , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Estudos de Viabilidade , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Leucovorina/administração & dosagem , Masculino , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Assistência Perioperatória , Prognóstico , Estudos Prospectivos , Qualidade de Vida , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Taxoides/administração & dosagemRESUMO
The present study evaluated the effects of physical exercise on heart rate variability (HRV) in cancer patients. 3 matched groups of each 15 tumour patients (60.4±8.9 years, 27 male, 18 female) were recruited: Physical exercise group 1 (acute treatment), Physical exercise group 2 (post treatment) and non-intervention group (acute treatment, no exercise). Exercise group patients received counselling for exercise and participated in a Nordic-Walking program. Short-term HRV-recordings, assessments of fatigue and quality of life (QoL) were performed prior to and 16 weeks after the exercise program initiation. MANCOVA revealed group × time differences in total power frequency domain of HRV and QoL (p<0.05). TP follow-up scores [logms(2)] differed significantly between non-intervention and intervention post treatment (2.0±0.5 vs. 2.6±0.5), but not between non-intervention and intervention during acute treatment. QoL follow-up scores differed significantly between non-intervention and intervention during acute treatment (47±15 vs. 64±18) and post treatment (47±15 vs. 69±19). Exercise enhances cardiac autonomic regulation of tumour patients during and after acute treatment. Because of the association of higher HRV-parameters and prolonged survival in cancer patients, improvement in autonomic control may be an important goal of exercise.
Assuntos
Terapia por Exercício/métodos , Frequência Cardíaca/fisiologia , Neoplasias/terapia , Qualidade de Vida , Idoso , Aconselhamento , Fadiga/etiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/psicologia , Estudos Prospectivos , Fatores de Tempo , Caminhada/fisiologiaRESUMO
UNLABELLED: : The German Commission on Hospital Hygiene and Infection Prevention has published several recommendations regarding hygiene in the intensive care unit. Compliance with these recommendations was surveyed. METHODS: In 2005 and 2011, the intensive care units of all hospitals in Frankfurt am Main, Germany, were examined by members of the public health department, using a checklist based on the respective recommendations. RESULTS: Recommendations on the architecture and function of intensive care wards were almost fully complied with, except for the stipulated amount of space and nursing personnel. Compliance with recommendations for prevention of ventilator-associated pneumonia and for prevention of catheter-related bloodstream infections was excellent, with only some minor exceptions. Regarding hand hygiene, in 2011 fewer faults were documented than in 2005. All hospitals took part in the German project of the world-wide campaign "clean care is safer care." In 2005, device-associated infections were surveyed in 92% intensive care units, and in 2011 in all of them. By 2011, screening of methicillin-resistant Staphylococcus aureus had been established in all intensive care units. CONCLUSION: Most problems that were observed regarded a scarcity of space and of facilities for isolation of patients and of nursing personnel. Improvements were seen in hand hygiene and in screening for multidrug resistant organisms (MDRO).
Assuntos
Controle de Doenças Transmissíveis/métodos , Infecção Hospitalar/prevenção & controle , Higiene/normas , Unidades de Terapia Intensiva Neonatal/normas , Unidades de Terapia Intensiva/normas , Bacteriemia/prevenção & controle , Infecções Relacionadas a Cateter/prevenção & controle , Lista de Checagem , Controle de Doenças Transmissíveis/organização & administração , Infecção Hospitalar/transmissão , Alemanha , Fidelidade a Diretrizes/organização & administração , Desinfecção das Mãos/normas , Humanos , Recém-Nascido , Unidades de Terapia Intensiva/organização & administração , Unidades de Terapia Intensiva Neonatal/organização & administração , Programas de Rastreamento/organização & administração , Staphylococcus aureus Resistente à Meticilina , Pneumonia Associada à Ventilação Mecânica/prevenção & controle , Infecções Estafilocócicas/prevenção & controle , Infecções Estafilocócicas/transmissãoRESUMO
BACKGROUND: To determine whether human epidermal growth factor receptor 2 (HER2) status is an independent prognostic factor in metastatic gastric and gastroesophageal junction (GEJ) adenocarcinoma. PATIENTS AND METHODS: Formalin-fixed paraffin-embedded tumor samples from 381 metastatic gastric/GEJ cancer patients enrolled at Krankenhaus Nordwest and Memorial Sloan-Kettering Cancer Centers on six first-line trials of chemotherapy without trastuzumab were examined for HER2 by immunohistochemistry (IHC) and in situ hybridization (ISH). IHC 3+ or ISH-positive tumors were considered HER2 positive. RESULTS: Seventy-eight of 381 patients (20%) had HER2-positive disease. In the multivariate logistic model, there were significantly higher rates of HER2 positivity in patients with liver metastasis (liver metastasis 31%; no liver metastasis 11%; P = 0.025) and intestinal histology (intestinal 33%; diffuse/mixed 8%; P = 0.001). No significant differences in HER2 positivity were found between resections and biopsies or primaries and metastases. Patients with HER2-positive gastric cancer had longer median overall survival compared with HER2-negative gastric cancer patients (13.9 versus 11.4 months, P = 0.047), but multivariate analysis indicated that HER2 status was not an independent prognostic factor (hazard ratio 0.79; 0.44-1.14; P = 0.194). CONCLUSIONS: Approximately 20% of Western patients with metastatic gastric cancer are HER2 positive. Unlike breast cancer, HER2 positivity is not independently prognostic of patient outcome in metastatic gastric or GEJ.
Assuntos
Neoplasias Esofágicas/patologia , Junção Esofagogástrica/patologia , Metástase Neoplásica , Neoplasias Gástricas/patologia , Neoplasias Esofágicas/metabolismo , Europa (Continente) , Humanos , Imuno-Histoquímica , Hibridização In Situ , Prognóstico , Neoplasias Gástricas/metabolismo , Estados UnidosRESUMO
BACKGROUND: The AIO KRK-0306 trial compares the efficacy of infusional 5-fluorouracil, folinic acid, irinotecan (FOLFIRI) plus cetuximab with FOLFIRI plus bevacizumab in first-line treatment of metastatic colorectal cancer (mCRC). In October 2008, an amendment terminated the inclusion of patients with KRAS-mutated tumours. This subgroup of patients is evaluated in the present analysis, while the study is ongoing for patients with KRAS wild-type tumours. METHODS: Patients were randomly assigned to FOLFIRI (Tournigand regimen) every 2 weeks plus cetuximab (400 mg/m2 day 1, followed by 250 mg/m2 weekly=arm A) or bevacizumab (5 mg/kg every 2 weeks=arm B). Among 336 randomised patients, KRAS mutation was demonstrated in 100 assessable patients. The primary study end point was objective response rate (ORR). RESULTS: ORR was 44% [95% confidence interval (CI) 29% to 59%] in arm A versus 48% (95% CI, 33% to 62%) in arm B. Progression-free survival was 7.5 versus 8.9 months (hazard ratio: 1.0) and overall survival was 22.7 versus 18.7 months (hazard ratio: 0.86) in arms A versus B, respectively. CONCLUSIONS: This is the first head to head comparison of cetuximab versus bevacizumab in first-line treatment of mCRC. In the present evaluation of patients with KRAS-mutated tumours, neither strategy demonstrated a clearly superior outcome.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Proteínas Proto-Oncogênicas/genética , Proteínas ras/genética , Adenocarcinoma/genética , Adenocarcinoma/mortalidade , Adenocarcinoma/secundário , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Cetuximab , Códon , Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Alemanha , Humanos , Irinotecano , Estimativa de Kaplan-Meier , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Mutação , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Proteínas Proto-Oncogênicas p21(ras) , Resultado do Tratamento , Suspensão de TratamentoRESUMO
BACKGROUND: The prognostic role of matrix metalloproteinase-9 (MMP-9) in metastatic gastric cancer has not been validated. PATIENTS AND METHODS: We carried out a molecular analysis in 222 metastatic gastric cancer patients obtained from clinical trials. We assessed the messenger RNA (mRNA) expression of MMP-9, vascular endothelial growth factor receptor-A, and epidermal growth factor receptor in a training cohort of 130 patients and conducted an independent validation in 92 patients. Automated RNA extraction from paraffin and RT-quantitative PCR was used. Immunohistochemistry for MMP-9 and diverse immune cell infiltrates was conducted. RESULTS: In the training cohort, only MMP-9 significantly correlated with patient's survival. At the cut-off with the highest predictive value, 19% of patients had MMP-9 expression above this cut-off and these showed a median survival of 3.6 months compared with 10.5 months (P=1.7e(-6)) in patients with lower expression. Corresponding 1- and 2-year survivals were 9% and 44% and 0 and 21%, respectively. The application of this cut-off to the validation cohort revealed similar distributions of overall survival according to MMP-9 expression on uni- (P<0.001) and multivariate analyses (P<0.001). No differences in survival according to MMP-9 below best cut-off were found. MMP-9 protein assessed by immunohistochemistry was not prognostic. CONCLUSION: MMP-9 mRNA expression above a certain cut-off level is associated with dismal survival.
Assuntos
Adenocarcinoma/enzimologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Expressão Gênica , Metaloproteinase 9 da Matriz/genética , Neoplasias Gástricas/enzimologia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/mortalidade , Adenocarcinoma/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Cisplatino/administração & dosagem , Ensaios Clínicos Fase III como Assunto , Docetaxel , Receptores ErbB/genética , Receptores ErbB/metabolismo , Feminino , Fluoruracila/administração & dosagem , Humanos , Estimativa de Kaplan-Meier , Leucovorina/administração & dosagem , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Pessoa de Meia-Idade , Análise Multivariada , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Taxoides/administração & dosagem , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
BACKGROUND: Rituximab plus combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is widely recommended for the treatment of aggressive B-cell lymphomas. However, there is very little information regarding the management of elderly patients. PATIENTS AND METHODS: We initiated a phase II study of first-line treatment with rituximab and bendamustine in elderly patients (≥80 years) with aggressive B-cell lymphomas who were not eligible for R-CHOP or who did not agree to aggressive treatment. The treatment decision on eligibility for R-CHOP was left to discretion of the physicians. RESULTS: Fourteen patients with a median age of 85 years (range 80-95 years) were included. The age-adjusted international prognostic index was zero in five patients, one in three patients, and two in six patients. Thirteen patients were assessable for response. Seven patients (54%) had a complete response, two (15%) a partial response, and four (31%) progressive disease. The median overall survival was 7.7 months, and the median progression-free survival 7.7 months; however, six patients (43%) were alive without disease at 20-72 months from the start of treatment. Major toxicity was neutropenia (17% grade 3 and 6% grade 4). All other grade 3 and 4 hematotoxicities and non-hematological toxic effects ranged between 2% and 11% CONCLUSIONS: Because of its efficacy and low toxicity, bendamustine in combination with rituximab may be an alternative treatment for aggressive lymphomas in old patients not eligible for R-CHOP. These results, however, need to be confirmed in larger studies.
Assuntos
Anticorpos Monoclonais Murinos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma de Células B/tratamento farmacológico , Compostos de Mostarda Nitrogenada/administração & dosagem , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/efeitos adversos , Cloridrato de Bendamustina , Intervalo Livre de Doença , Feminino , Humanos , Linfoma de Células B/patologia , Masculino , Estadiamento de Neoplasias , Neutropenia/etiologia , Compostos de Mostarda Nitrogenada/efeitos adversos , RituximabRESUMO
BACKGROUND: The aim of this study was to determine the activity of anthracycline rechallenge using pegylated liposomal doxorubicin (PLD) in patients with metastatic breast cancer (MBC) previously treated with conventional anthracyclines. METHODS: Pooled individual data from four prospective trials were used, and the primary end point of the pooled analysis was clinical benefit rate (CBR). The studies comprised 935 patients, of whom 274 had received PLD in the metastatic setting after prior exposure to conventional anthracyclines (rechallenge population). RESULTS: The majority of patients were heavily pretreated. Previous anthracycline therapy was administered in the adjuvant (14%) or metastatic setting (46%), or both (40%). The overall CBR from rechallenge with PLD was 37.2% (95% CI, 32.4-42.0). In univariate analyses, the CBR was significantly higher in patients with less exposure to prior chemotherapy, in taxane-naive patients, and in patients with a favourable Eastern Cooperative Group performance status of 0 vs 1 vs 2 (53.3 vs 35.5 vs 18.2%; P<0.001). In multivariate analyses, performance status proved to be the only independent predictor of the CBR achieved with PLD rechallenge (P=0.038). There was no statistically significant difference in CBR regarding the setting, cumulative dose of and/or resistance to prior anthracyclines, or time since prior anthracycline administration. CONCLUSION: Anthracycline rechallenge using PLD is effective in patients with MBC who have a favourable performance status, regardless of setting, resistance, cumulative dose or time since prior conventional anthracycline therapy.