RESUMO
BACKGROUND: Concurrent chemotherapy and thoracic radiotherapy followed by prophylactic cranial irradiation (PCI) is the standard treatment in limited-disease small-cell lung cancer (LD-SCLC), with 5-year overall survival (OS) of only 25% to 33%. PATIENTS AND METHODS: STIMULI is a 1:1 randomised phase II trial aiming to demonstrate superiority of consolidation combination immunotherapy versus observation after chemo-radiotherapy plus PCI (protocol amendment-1). Consolidation immunotherapy consisted of four cycles of nivolumab [1 mg/kg, every three weeks (Q3W)] plus ipilimumab (3 mg/kg, Q3W), followed by nivolumab monotherapy (240 mg, Q2W) for up to 12 months. Patient recruitment closed prematurely due to slow accrual and the statistical analyses plan was updated to address progression-free survival (PFS) as the only primary endpoint. RESULTS: Of the 222 patients enrolled, 153 were randomised (78: experimental; 75: observation). Among the randomised patients, median age was 62 years, 60% males, 34%/65% current/former smokers, 31%/66% performance status (PS) 0/1. Up to 25 May 2020 (median follow-up 22.4 months), 40 PFS events were observed in the experimental arm, with median PFS 10.7 months [95% confidence interval (CI) 7.0-not estimable (NE)] versus 42 events and median 14.5 months (8.2-NE) in the observation, hazard ratio (HR) = 1.02 (0.66-1.58), two-sided P = 0.93. With updated follow-up (03 June 2021; median: 35 months), median OS was not reached in the experimental arm, while it was 32.1 months (26.1-NE) in observation, with HR = 0.95 (0.59-1.52), P = 0.82. In the experimental arm, median time-to-treatment-discontinuation was only 1.7 months. CTCAE v4 grade ≥3 adverse events were experienced by 62% of patients in the experimental and 25% in the observation arm, with 4 and 1 fatal, respectively. CONCLUSIONS: The STIMULI trial did not meet its primary endpoint of improving PFS with nivolumab-ipilimumab consolidation after chemo-radiotherapy in LD-SCLC. A short period on active treatment related to toxicity and treatment discontinuation likely affected the efficacy results.
Assuntos
Neoplasias Pulmonares , Nivolumabe , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimiorradioterapia/efeitos adversos , Feminino , Humanos , Ipilimumab/efeitos adversos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: In a Spanish Lung Cancer Group (SLCG) phase II trial, the combination of BRCA1 and receptor-associated protein 80 (RAP80) expression was significantly associated with outcome in Caucasian patients with nonsmall-cell lung cancer (NSCLC). The SLCG therefore undertook an industry-independent collaborative randomized phase III trial comparing nonselected cisplatin-based chemotherapy with therapy customized according to BRCA1/RAP80 expression. An analogous randomized phase II trial was carried out in China under the auspices of the SLCG to evaluate the effect of BRCA1/RAP80 expression in Asian patients. PATIENTS AND METHODS: Eligibility criteria included stage IIIB-IV NSCLC and sufficient tumor specimen for molecular analysis. Randomization to the control or experimental arm was 1 : 1 in the SLCG trial and 1 : 3 in the Chinese trial. In both trials, patients in the control arm received docetaxel/cisplatin; in the experimental arm, patients with low RAP80 expression received gemcitabine/cisplatin, those with intermediate/high RAP80 expression and low/intermediate BRCA1 expression received docetaxel/cisplatin, and those with intermediate/high RAP80 expression and high BRCA1 expression received docetaxel alone. The primary end point was progression-free survival (PFS). RESULTS: Two hundred and seventy-nine patients in the SLCG trial and 124 in the Chinese trial were assessable for PFS. PFS in the control and experimental arms in the SLCG trial was 5.49 and 4.38 months, respectively [log rank P = 0.07; hazard ratio (HR) 1.28; P = 0.03]. In the Chinese trial, PFS was 4.74 and 3.78 months, respectively (log rank P = 0.82; HR 0.95; P = 0.82). CONCLUSION: Accrual was prematurely closed on the SLCG trial due to the absence of clinical benefit in the experimental over the control arm. However, the BREC studies provide proof of concept that an international, nonindustry, biomarker-directed trial is feasible. Thanks to the groundwork laid by these studies, we expect that ongoing further research on alternative biomarkers to elucidate DNA repair mechanisms will help define novel therapeutic approaches. TRIAL REGISTRATION: NCT00617656/GECP-BREC and ChiCTR-TRC-12001860/BREC-CHINA.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Proteína BRCA1/biossíntese , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Proteínas de Transporte/biossíntese , Proteínas Nucleares/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , China , Cisplatino/administração & dosagem , Proteínas de Ligação a DNA , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Docetaxel , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Chaperonas de Histonas , Humanos , Masculino , Pessoa de Meia-Idade , Taxoides/administração & dosagem , Resultado do Tratamento , População Branca , GencitabinaRESUMO
BACKGROUND: Docetaxel and irinotecan chemotherapy have shown good efficacy in the treatment of advanced oesophago-gastric cancer. This randomised phase II study evaluated the efficacy and toxicity profile of two non-platinum docetaxel-based doublet regimens in advanced oesophago-gastric cancer. METHODS: Chemotherapy-naïve patients with advanced oesophago-gastric cancer were randomised to receive either 3-weekly DI (docetaxel 60 mg m(-2) plus irinotecan 250 mg m(-2) (Day 1)) or 3-weekly DF (docetaxel 85 mg m(-2) (Day 1) followed by 5-fluorouracil 750 mg m(-2) per day as a continuous infusion (Days 1-5)). RESULTS: A total of 85 patients received DI (n=42) or DF (n=43). The primary endpoint was overall response rate (ORR). The ORR and time to progression (TTP) in the evaluable population (n=65) were 37.5% (DI) vs 33.3% (DF), and 4.2 months vs 4.4 months, respectively. In the intent-to-treat population, the observed ORR, TTP and median overall survival were similar between the two groups. Grade 3-4 neutropenia, febrile neutropenia and diarrhoea were more frequent in the DI arm as compared with the DF arm (83.3% vs 69.8%, 40.5% vs 18.6%, and 42.9% vs 16.3%, respectively). CONCLUSION: Both docetaxel-based doublet regimens show comparable efficacy; however, the DF regimen was associated with a better toxicity profile and is an alternative treatment option for patients in whom platinum-based regimens are unsuitable.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Progressão da Doença , Docetaxel , Feminino , Fluoruracila/administração & dosagem , Humanos , Irinotecano , Masculino , Pessoa de Meia-Idade , Taxoides/administração & dosagemRESUMO
PURPOSE: The analysis of epidermal growth factor receptor (EGFR) mutations in many patients with advanced non-small-cell lung cancer (aNSCLC) has provided the opportunity for successful treatment with specific, targeted EGFR tyrosine kinase inhibitors. However, this therapeutic decision may be challenging when insufficient tumor tissue is available for EGFR mutation testing. Therefore, blood surrogate samples for EGFR mutation analysis have been suggested. METHODS: Data were collected from the Spanish cohort of patients in the large, non-interventional, diagnostic ASSESS study (NCT01785888) evaluating the utility of circulating free tumor-derived DNA from plasma for EGFR mutation testing. The incidence of EGFR mutation in Spain and the level of concordance between matched tissue/cytology and plasma samples were evaluated. RESULTS: In a cohort of 154 eligible patients, EGFR mutations were identified in 15.1 and 11.0% of tumor and plasma samples, respectively. The most commonly used EGFR mutation testing method for the tumor tissue samples was the QIAGEN Therascreen® EGFR RGQ PCR kit (52.1%). Fragment Length Analysis + PNA LNA Clamp was used for the plasma samples. The concordance rate for EGFR mutation status between the tissue/cytology and plasma samples was 88.8%; the sensitivity was 45.5%, and the specificity was 96.7%. CONCLUSIONS: The high concordance between the different DNA sources for EGFR mutation testing supports the use of plasma samples when tumor tissue is unavailable.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , DNA Tumoral Circulante/análise , Análise Mutacional de DNA/métodos , Neoplasias Pulmonares/genética , Adulto , Idoso , DNA Tumoral Circulante/genética , Receptores ErbB/sangue , Receptores ErbB/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Reação em Cadeia da Polimerase/métodos , Sensibilidade e Especificidade , EspanhaRESUMO
INTRODUCTION: Sorafenib improves progression-free survival in advanced clear-cell renal-cell carcinoma patients progressing to first-line therapy, as has been shown in the placebo-controlled international TARGET trial. The aim of this study is to report the results of the patients included in the Spanish centres in this trial. PATIENTS AND METHODS: The records of the patients in the database of the TARGET trial have been reviewed. Data about progression-free survival, overall survival and toxicity have been collected in order to do this subpopulation analysis. RESULTS: A total of 15 patients have been included (sorafenib arm 7, placebo arm 8). A trend to an improved progression-free survival in the sorafenib arm has been observed period Toxicity in the sorafenib arm has been manageable. CONCLUSION: The analysis of these 15 patients has shown efficacy and toxicity results that follow the trend observed for the overall international population.
Assuntos
Antineoplásicos/uso terapêutico , Benzenossulfonatos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Piridinas/uso terapêutico , Idoso , Antineoplásicos/efeitos adversos , Benzenossulfonatos/efeitos adversos , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Niacinamida/análogos & derivados , Compostos de Fenilureia , Piridinas/efeitos adversos , Sorafenibe , Espanha , Resultado do TratamentoRESUMO
PURPOSE: To describe healthcare professional (HCP) and patient time and related costs associated with trastuzumab intravenous infusion (IV) and trastuzumab subcutaneous (SC) formulations in patients with HER2-positive early breast cancer. METHODS: This prospective, observational time, and motion study in three Spanish centers was run as a substudy of the PrefHer trial. We recorded active HCP time for trastuzumab SC and IV-related tasks and calculated HCP time as the mean sum of task times over 154 administrations (80 IV, 74 SC). We calculated mean patient infusion chair time and treatment room time. Staff costs were calculated using fully loaded salary costs based on Spanish salaries ( 2012). RESULTS: The transition from trastuzumab IV to SC led to a 50% reduction in active HCP time [27.2 min (95% CI 21.8-32.6) vs. 13.2 min (95% CI 8.9-17.5) per cycle]. Time savings resulted from avoiding IV catheter installation and removal, line flushing, and drug reconstitution. SC administration led to a fivefold reduction (78-85%) in chair time and a fourfold reduction (59-81%) in patient treatment room time, resulting in 24 h free-up time in the total treatment course (18 cycles). Total estimated direct costs were 29,431.75 and 28,452.12 for IV and SC, respectively, a saving of 979.60 over a full treatment course. CONCLUSIONS: Trastuzumab SC provided substantial time savings for HCP and patients, and reduced staff costs vs. trastuzumab IV. Reducing the use of hospital facilities may result in further savings and improved quality of medical care.
Assuntos
Administração Intravenosa/economia , Antineoplásicos/economia , Neoplasias da Mama/economia , Custos e Análise de Custo , Injeções Subcutâneas/economia , Receptor ErbB-2/metabolismo , Trastuzumab/economia , Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Espanha , Trastuzumab/administração & dosagemRESUMO
This review highlights the numerous molecular biology findings in the field of lung cancer with potential therapeutic impact in both the near and distant future. Abundant pre-clinical and clinical data indicate that BRCA1 mRNA expression is a differential modulator of chemotherapy sensitivity. Low levels predict cisplatin sensitivity and antimicrotubule drug resistance, and the opposite occurs with high levels. The main core of recent research has centered on epidermal growth factor receptor (EGFR) mutations and gene copy numbers. For the first time, EGFR mutations have been shown to predict dramatic responses in metastatic lung adenocarcinomas, with a threefold increase in time to progression and survival in patients receiving EGFR tyrosine-kinase inhibitors. Evidence has also been accumulated on the crosstalk between estrogen and EGFR receptor pathways, paving the way for clinical trials of EGFR tyrosine-kinase inhibitors plus aromatase inhibitors. Understanding the relevance of these findings can help to change the clinical practice in oncology towards customizing chemotherapy and targeted therapies, leading to improvement both in survival and in cost-effectiveness.
Assuntos
Carcinoma Broncogênico/tratamento farmacológico , Carcinoma Broncogênico/mortalidade , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Biomarcadores , Carcinoma Broncogênico/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Humanos , Neoplasias Pulmonares/genética , Mutação , Prognóstico , Taxa de SobrevidaRESUMO
PURPOSE: To compare the survival benefit obtained with cisplatin plus gemcitabine, a cisplatin-based triplet, and nonplatinum sequential doublets in advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Stage IIIB to IV NSCLC patients were randomly assigned to receive cisplatin 100 mg/m2 day 1 plus gemcitabine 1,250 mg/m2 days 1 and 8, every 3 weeks for six cycles (CG); cisplatin 100 mg/m2 day 1 plus gemcitabine 1,000 mg/m2 and vinorelbine 25 mg/m2 days 1 and 8, every 3 weeks for six cycles (CGV); or gemcitabine 1,000 mg/m2 plus vinorelbine 30 mg/m2 days 1 and 8, every 3 weeks for three cycles, followed by vinorelbine 30 mg/m2 days 1 and 8 plus ifosfamide 3 g/m2 day 1, every 3 weeks for three cycles (GV-VI). RESULTS: Five hundred fifty-seven patients were assigned to treatment (182 CG, 188 CGV, 187 GV-VI). Response rates were significantly inferior for the nonplatinum sequential doublet (CG, 42%; CGV, 41%; GV-VI, 27%; CG v GV-VI, P =.003). No differences in median survival or time to progression were observed. Toxicity was higher for the triplet: grade 3 to 4 neutropenia (GC, 32%; CGV, 57%; GV-VI, 27%; P <.05); neutropenic fever (CG, 4%; CGV, 19%; GV-VI, 5%; P <.0001); grade 3 to 4 thrombocytopenia (CG, 19%; CGV, 23%; GV-VI, 3%; P =.0001); and grade 3 to 4 emesis (GC, 22%; GCV, 32%; GV-VI, 6%; P <.0001). CONCLUSION: On the basis of these results, CG remains a standard regimen for first-line treatment of advanced NSCLC.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cisplatino/administração & dosagem , Desoxicitidina/análogos & derivados , Desoxicitidina/administração & dosagem , Ifosfamida/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Vimblastina/análogos & derivados , Vimblastina/administração & dosagem , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Progressão da Doença , Relação Dose-Resposta a Droga , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Espanha , Análise de Sobrevida , Resultado do Tratamento , Vinorelbina , GencitabinaRESUMO
A phase II multicentre study of a 3-week schedule of irinotecan (CPT-11) and cisplatin providing the highest recommended dose intensity of both agents in combination, was conducted in patients with advanced non-small cell lung cancer (NSCLC). Seventy-four stage IIIB (not suitable for radiotherapy) or stage IV NSCLC patients were enrolled to receive CPT-11 200 mg/m(2) i.v. and cisplatin 80 mg/m(2) i.v. on day 1 every 3 weeks. Relative dose-intensities for CPT-11 and cisplatin were 92 and 95%, respectively. No complete responses were observed. Twenty-five patients out of 73 obtained a partial response (34.2%). Partial responses were confirmed in 18 patients (24.7%: 95% CI, 15.3-36.1%). Median survival overall was 8.2 months, 9.7 months for patients with baseline performance status (PS) 0 and 1, and 4 months for patients with PS 2. The 1-year survival rate was 31%. Major clinical toxicities were grade 3 and 4 delayed diarrhoea (29% of patients) and febrile neutropenia (14% of patients). In conclusion, the present once-every-3-week schedule of CPT-11 and cisplatin is feasible and active in PS 0-1 advanced NSCLC patients, but results do not seem superior to those reported with other schedules.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camptotecina/análogos & derivados , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/secundário , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/administração & dosagem , Carcinoma de Células Grandes/tratamento farmacológico , Carcinoma de Células Grandes/patologia , Carcinoma de Células Grandes/secundário , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/secundário , Cisplatino/administração & dosagem , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Irinotecano , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Taxa de Sobrevida , Resultado do TratamentoRESUMO
A new schedule with cisplatin and gemcitabine administered biweekly was prospectively evaluated in stage IIIB or IV non-small cell lung cancer. We report the interim analysis of the safety and efficacy with the first 23 patients included. The mean age was 60. Thirteen patients (56.5%) were stage IIIB and 10 (43.5%) were stage IV The overall response rate was 47.8%: 69.2% for stage IIIB and 20% for stage IV The median survival among the 23 patients was 33 weeks and 1-year survival was 39%: 53.8% for stage IIIB and 20% for stage IV Seventy-seven cycles (154 administrations) were given. The mean number of cycles/patient was 3.3 (range: 1 to 6). Of the 154 administrations, 26 were delayed 1 week for recovery from toxicity. The dose intensity (Hryniuk criteria) was 94% of the planned dose. There was one toxic death with grade 4 thrombocytopenia and grade 4 esophagitis. In two patients, grade 3-4 vascular toxicity was observed, with distal arterial ischemic changes in the lower extremities. There were three (3.9%) episodes of grade 2 neutropenia, one (1.7%) of grade 3 and another one of grade 4. No cases of febrile neutropenia were seen. Predominant nonhematologic toxicities were asthenia and nausea/vomiting. This schedule of cisplatin and gemcitabine has a good therapeutic index and, as it is active, enrollment is ongoing to complete the second part of the study.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Desoxicitidina/análogos & derivados , Neoplasias Pulmonares/tratamento farmacológico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/mortalidade , Adulto , Idoso , Carcinoma/tratamento farmacológico , Carcinoma/mortalidade , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/mortalidade , Cisplatino/administração & dosagem , Intervalos de Confiança , Desoxicitidina/administração & dosagem , Esquema de Medicação , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Taxa de Sobrevida , GencitabinaRESUMO
Some proteolytic enzymes, trypsin, cathepsin B, cathepsin D, collagenase, elastase and their inhibitors, API and AMG, in serum of patients with colorectal carcinoma have been evaluated. Twenty patients belonged to stage B of colorectal carcinoma, twenty two patients to stage D (Astler and Coller classification) and a control group of thirty healthy volunteers were evaluated. Except in cathepsin D, patients exhibit higher enzymatic activities than healthy subjects, and both groups have all the proteolytic activities assayed in serum. Patients with disseminated disease have increased cathepsin B and collagenase levels, with a decrease of trypsin activity, showing an increment in API and AMG in sera. However, only the API values were significantly higher in patients with metastases. The coexistence of proteolytic activities in human sera together with their inhibitors is considered as well as the origin of these, tumoral and/or reactive, increments. Cathepsin B levels are raised in colorectal neoplasms and contribute to the destruction of the extracellular matrix and the proliferation of tumoral cells. There is evidence that a relation between collagenase like activity and tumor invasiveness exists. Cathepsin B and collagenase increases agree with the tumoral mass. On the other hand, trypsin decrease in metastatic carcinoma is probably related to the increment of their inhibitors, API and AMG, acute phase reactant proteins.
Assuntos
Neoplasias Colorretais/enzimologia , Endopeptidases/sangue , alfa 1-Antitripsina/análise , alfa-Macroglobulinas/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Catepsinas/sangue , Colagenases/sangue , Neoplasias Colorretais/sangue , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Elastase Pancreática/sangue , Tripsina/sangueRESUMO
OBJECTIVE: To analyze the diagnostic accuracy of the following parameters in the diagnosis of pancreatic cancer: carcinoembryonic antigen (CEA), tissue plasminogen activator (TPA), carbohydrate antigen 19-9 (CA 19-9), carbohydrate antigen 50 (CA 50), alpha-1-antitrypsin (AAT), alpha-2 macroglobulin (AMG), and ceruloplasmin (CP). PATIENTS AND MENTOD: We prospectively studied 58 patients with pancreatic cancer, 40 with alcoholic pancreatitis and 40 healthy controls, in whom the above-mentioned parameters were analyzed. Receiver operating characteristic curves (ROC curves) were analyzed. RESULTS: The specificity of TPA, CA 19-9 and CA 50 in the differential diagnosis between pancreatic cancer and chronic pancreatitis was 87.5%, 90% and 95% respectively, with a sensitivity of nearly 90%. Although levels of AAT, AMG and CP were higher in patients with cancer than in those with pancreatitis, their specificity was lower, approximately 65%. CEA and TPA showed a positive association with the presence of metastases. CONCLUSION: TPA, CA 19-9 and CA 50 were useful in the differential diagnosis between pancreatic cancer and chronic pancreatitis.
Assuntos
Proteínas de Fase Aguda , Biomarcadores Tumorais , Neoplasias Pancreáticas/diagnóstico , Proteínas de Fase Aguda/análise , Idoso , Biomarcadores Tumorais/sangue , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/sangue , Estudos Prospectivos , Curva ROC , Sensibilidade e EspecificidadeRESUMO
Adrenal insufficiency or Addison's disease is actually a rare illness associated with numerous pathologies. We describe the case of a fifty years old male with lung adenocarcinoma and metastasis in both adrenal glands, who was receiving chemotherapy with mytomicin, ifosfamide and cisplatin (MIC), and was diagnosed of adrenal insufficiency as a result of acute episode addisonian crisis. Many times, the clinic symptoms of adrenal insufficiency can go unnoticed due to its low specifity and to mixing up with other syndromes. Hypoadrenalism has been described in association with many tumours, specially with non-Hodgkin's lymphoma. It seems that there is a discordance between the number of patients with bilateral metastatic adrenal destruction and the documented cases of clinic insufficiency. Once the adrenal failure is suspected, the diagnosis and hormone replacement treatment are really easy. Addison's disease ethiologies are revised putting special emphasis on those related with cancer patients.
Assuntos
Doença de Addison/etiologia , Adenocarcinoma/complicações , Neoplasias das Glândulas Suprarrenais/complicações , Neoplasias Pulmonares/complicações , Adenocarcinoma/secundário , Neoplasias das Glândulas Suprarrenais/secundário , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-IdadeAssuntos
Neoplasias Colorretais/complicações , Endocardite Bacteriana/complicações , Endocardite Bacteriana/tratamento farmacológico , Infecções Estreptocócicas/complicações , Infecções Estreptocócicas/tratamento farmacológico , Streptococcus gordonii , Antibacterianos/uso terapêutico , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/microbiologia , Ecocardiografia Transesofagiana , Endocardite Bacteriana/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência da Valva Mitral/complicações , Metástase Neoplásica , Infecções Estreptocócicas/diagnóstico por imagemRESUMO
INTRODUCTION: The haemostatic system plays an important role in the process of cancer development and spread. Anticoagulants, mainly low molecular weight heparins, could prolong survival in cancer patients, particularly in patients with lung cancer, beyond prevention of thromboembolic events. METHODS: In a multicenter, investigator-initiated, open-label, randomized, sequential study, 38 patients with newly-diagnosed, limited-stage small-cell lung cancer were randomized to receive standard chemoradiotherapy or the same therapy plus 3,500 IU daily of bemiparin for a maximum of 26 weeks. The primary outcome was progression-free survival. RESULTS: The study was terminated early due to slow recruitment. Median progression-free survival was 272 days with chemoradiotherapy alone and 410 days in the bemiparin group; hazard ratio, 2.58 (95% confidence interval [CI], 1.15-5.80); p=0.022. Median overall survival was 345 days with chemoradiotherapy alone and 1133 days in the bemiparin group; hazard ratio, 2.96 (95% CI, 1.22-7.21); p=0.017. The rate of tumor response was similar in both study arms. There was no significant between-group difference in the rates of major bleeding. Toxicity related with the experimental treatment was minimal. CONCLUSION: The addition of bemiparin to first line therapy with chemoradiotherapy significantly increases survival in patients with newly-diagnosed, limited-stage small-cell lung cancer. (Funded by the Instituto Científico y Tecnológico, University of Navarra. ClinicalTrials.gov identifier: NCT00324558).