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INTRODUCTION: Amivantamab-vmjw (amivantamab) is a bispecific EGFR/MET antibody approved for patients with advanced NSCLC with EGFR exon 20 insertion mutations, after prior therapy. Nevertheless, the benefits and safety of amivantamab in other EGFR-mutant lung cancer, with or without osimertinib, and with concurrent radiation therapy, are less known. METHODS: We queried the MD Anderson Lung Cancer GEMINI, Fred Hutchinson Cancer Research Center, University of California Davis Comprehensive Cancer Center, and Stanford Cancer Center's database for patients with EGFR-mutant NSCLC treated with amivantamab, not on a clinical trial. The data analyzed included initial response, duration of treatment, and concomitant radiation safety in overall population and prespecified subgroups. RESULTS: A total of 61 patients received amivantamab. Median age was 65 (31-81) years old; 72.1% were female; and 77% were patients with never smoking history. Median number of prior lines of therapies was four. On the basis of tumor's EGFR mutation, 39 patients were in the classical mutation cohort, 15 patients in the exon 20 cohort, and seven patients in the atypical cohort. There were 37 patients (58.7%) who received amivantamab concomitantly with osimertinib and 25 patients (39.1%) who received concomitant radiation. Furthermore, 54 patients were assessable for response in the overall population; 19 patients (45.2%) had clinical response and disease control rate (DCR) was 64.3%. In the classical mutation cohort of the 33 assessable patients, 12 (36.4%) had clinical response and DCR was 48.5%. In the atypical mutation cohort, six of the seven patients (85.7%) had clinical response and DCR was 100%. Of the 13 assessable patients in the exon 20 cohort, five patients (35.7%) had clinical response and DCR was 64.3%. Adverse events reported with amivantamab use were similar as previously described in product labeling. No additional toxicities were noted when amivantamab was given with radiation with or without osimertinib. CONCLUSIONS: Our real-world multicenter analysis revealed that amivantamab is a potentially effective treatment option for patients with EGFR mutations outside of exon 20 insertion mutations. The combination of osimertinib with amivantamab is safe and feasible. Radiation therapy also seems safe when administered sequentially or concurrently with amivantamab.
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Acrilamidas , Anticorpos Biespecíficos , Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Indóis , Neoplasias Pulmonares , Pirimidinas , Humanos , Feminino , Idoso , Adulto , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Masculino , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/induzido quimicamente , Antineoplásicos/uso terapêutico , Receptores ErbB/genética , Receptores ErbB/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/induzido quimicamente , Compostos de Anilina/farmacologia , Compostos de Anilina/uso terapêutico , Mutação , Inibidores de Proteínas Quinases/uso terapêuticoRESUMO
PURPOSE: Targeted Agent and Profiling Utilization Registry (TAPUR) is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and genomic alterations known to be drug targets. Results of a cohort of patients with soft tissue sarcoma with cyclin-dependent kinase 4 (CDK4) amplification treated with palbociclib are reported. METHODS: Eligible patients had measurable disease, Eastern Cooperative Oncology Group performance status 0 to 2, adequate organ function, and no standard treatment options. The primary end point was disease control (DC), defined as objective response (OR) or stable disease (SD) of at least 16+ weeks duration (SD16+) according to RECIST v1.1. The DC rate was estimated with a 90% CI. Secondary end points included OR, progression-free survival (PFS), overall survival (OS), duration of response, duration of SD, and safety. RESULTS: Forty-two patients with CDK4 amplification were enrolled. One patient was not evaluable for efficacy. One patient with partial response and 18 with SD16+ were observed for DC and OR rates of 46% (90% CI, 36 to 100) and 2% (95% CI, <1 to 13), respectively. Median PFS was 16 weeks (95% CI, 9 to 28) and median OS was 69 weeks (95% CI, 31 to 111) for evaluable patients. Twenty patients had at least one grade 3 to 4 adverse event (AE) at least possibly related to palbociclib, including alanine aminotransferase increase, anemia, fatigue, hypophosphatemia, leukopenia, neutropenia, and thrombocytopenia. No serious AEs were reported. CONCLUSION: Palbociclib met prespecified criteria to declare a signal of antitumor activity in patients with sarcoma and CDK4 amplification.
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Quinase 4 Dependente de Ciclina , Piperazinas , Piridinas , Sistema de Registros , Sarcoma , Humanos , Quinase 4 Dependente de Ciclina/genética , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Piridinas/uso terapêutico , Feminino , Masculino , Pessoa de Meia-Idade , Piperazinas/uso terapêutico , Adulto , Idoso , Sarcoma/tratamento farmacológico , Sarcoma/genética , Amplificação de Genes , Adulto Jovem , Idoso de 80 Anos ou maisRESUMO
PURPOSE: Targeted Agent and Profiling Utilization Registry is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and genomic alterations known to be drug targets. Results of a cohort of patients with biliary tract cancer (BTC) with ERBB2/3 amplification, overexpression, or mutation treated with pertuzumab plus trastuzumab are reported. METHODS: Eligible patients had advanced BTC, measurable disease (RECIST v1.1), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, tumors with ERBB2/3 alterations, and a lack of standard treatment options. Simon's two-stage design was used with a primary end point of disease control (DC), defined as objective response (OR) or stable disease of at least 16+ weeks duration (SD16+) according to RECIST v1.1. Secondary end points included OR, progression-free survival, overall survival, duration of response, duration of stable disease, and safety. RESULTS: Twenty-nine patients were enrolled from February 2017 to January 2022, and all had advanced BTC with an ERBB2/3 alteration. One patient was not evaluable for efficacy. One complete response, eight partial responses, and two SD16+ were observed for DC and OR rates of 40% (90% CI, 27 to 100) and 32% (95% CI, 16 to 52), respectively. The null hypothesis of 15% DC rate was rejected (P = .0015). Four patients had at least one grade 3 adverse event (AE) or serious AE at least possibly related to treatment: anemia, diarrhea, infusion-related reaction, and fatigue. CONCLUSION: Pertuzumab plus trastuzumab met prespecified criteria to declare a signal of activity in patients with BTC and ERBB2/3 amplification, overexpression, or mutation.
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(1) Background: The objective of this analysis was to evaluate the device usage rates and patterns of use regarding Tumor-Treating Fields (TTFields) for patients with malignant pleural mesothelioma (MPM) throughout the US. (2) Methods: We evaluated de-identified data from 33 patients with MPM enrolled in FDA-required HDE protocols at 14 institutions across the US from September 2019 to March 2022. (3) Results: The median number of total TTFields usage days was 72 (range: 6-649 days), and the total treatment duration was 160 months for all patients. A low usage rate (defined as less than 6 h per day, 25%) was observed in 34 (21.2%) months. The median TTFields usage in the first 3 months was 12 h per day (range: 1.9-21.6 h), representing 50% (range: 8-90%) of the potential daily duration. The median TTFields usage after 3 months decreased to 9.1 h per day (range: 3.1-17 h), representing 38% (range: 13-71%) of the daily duration, and was lower than usage in the first 3 months (p = 0.01). (4) Conclusions: This study represents the first multicenter analysis of real-world TTFields usage based on usage patterns for MPM patients in clinical practice. The real-world usage level was lower than the suggested daily usage. Further initiatives and guidelines should be developed to evaluate the impact of this finding on tumor control.
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Mesotelioma Maligno , Neoplasias , HumanosRESUMO
PURPOSE: The Targeted Agent and Profiling Utilization Registry Study is a pragmatic basket trial evaluating antitumor activity of commercially available targeted agents in patients with advanced cancers harboring potentially actionable genomic alterations. Data from a cohort of patients with lung cancer and ERBB2 mutation or amplification treated with pertuzumab plus trastuzumab (P + T) are reported. METHODS: Eligible patients had advanced lung cancer of any histology, no standard treatment options, measurable disease (RECIST v1.1), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and tumors with ERBB2 mutation or amplification. Simon's two-stage design was used with a primary end point of disease control (DC), defined as objective response (OR) per RECIST v. 1.1 or stable disease (SD) of at least 16 weeks duration (SD16+). Secondary end points included safety, duration of response, duration of SD, progression-free survival, and overall survival. RESULTS: Twenty-eight patients with lung cancer (27 non-small-cell, 1 small-cell) and ERBB2 mutation (n = 15), ERBB2 amplification (n = 12), or both (n = 1) were enrolled from November 2016 to July 2020. All patients were evaluable for efficacy and toxicity. Three patients with partial response (two ERBB2 mutation; one both mutation and amplification) and seven patients with SD16+ (five ERBB2 mutation; two amplification) were observed for a DC rate of 37% (95% CI, 21 to 50; P = .005) and OR rate of 11% (95% CI, 2 to 28). Five patients had one or more grade 3 or 4 adverse or serious adverse events at least possibly related to P + T. CONCLUSION: Combination P + T showed evidence of antitumor activity in heavily pretreated patients with non-small-cell lung cancer and ERBB2 mutation or amplification, particularly those with ERBB2 exon 20 insertion mutations.
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Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação , Receptor ErbB-2/genética , Trastuzumab/uso terapêuticoRESUMO
PURPOSE: The Targeted Agent and Profiling Utilization Registry (TAPUR) Study is a pragmatic basket trial evaluating antitumor activity of approved targeted agents in patients with advanced cancers harboring potentially actionable genomic alterations. Data from cohorts of patients with high tumor mutational burden (HTMB, defined as ≥9 mutations per megabase) with advanced colorectal cancer (CRC) and other advanced cancers treated with pembrolizumab are reported. METHODS: Eligible patients were 18 years and older with measurable tumors and a lack of standard treatment options, an Eastern Cooperative Oncology Group performance status of 0-1, and adequate organ function. The primary end point was disease control (DC), defined as complete or partial response or stable disease (SD) of at least 16-weeks duration. For the CRC cohort, Simon's two-stage design with a null DC rate of 15% versus 35% (power = 0.85; α = .10) was used. Low accruing histology-specific cohorts were collapsed into one histology-pooled (HP) cohort. For the HP cohort, the null hypothesis of a DC rate of 15% was rejected if the lower limit of a one-sided 90% CI was >15%. Secondary end points included objective response (OR), safety, progression-free survival, overall survival, duration of response, and duration of SD. RESULTS: Seventy-seven patients with HTMB with CRC (n = 28) or advanced cancers (n = 49) were treated with pembrolizumab. For the CRC cohort, the DC rate was 31% (P = .04) and the OR rate was 11%. For the HP cohort, the DC rate was 45% (one-sided 90% CI, 35 to 100) and the OR rate was 26%. The null hypothesis of a 15% DC rate was rejected for both cohorts. Twelve of 77 patients experienced treatment-related grade 3 adverse events (AEs) or serious AEs, including two deaths. CONCLUSION: Pembrolizumab demonstrated antitumor activity in pretreated patients with advanced cancers and HTMB.
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Antineoplásicos , Neoplasias Colorretais , Humanos , Antineoplásicos/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genéticaRESUMO
PURPOSE: The Targeted Agent and Profiling Utilization Registry Study is a phase II basket study evaluating antitumor activity of commercially available targeted agents in patients with advanced cancers with genomic alterations known to be drug targets. The results in a cohort of patients with solid tumors with BRAF mutations treated with cobimetinib plus vemurafenib are reported. METHODS: Eligible patients had measurable disease (RECIST v.1.1), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and no standard treatment options. The primary end point was disease control (DC), defined as complete response (CR) or partial response (PR) or stable disease of at least 16-weeks duration (SD16+). Low-accruing histology-specific cohorts with BRAF mutations treated with cobimetinib plus vemurafenib were collapsed into a single histology-pooled cohort for this analysis. The results were evaluated on the basis of a one-sided exact binomial test with a null DC rate of 15% versus 35% (power, .82; α, .10). The secondary end points were objective response (OR), progression-free survival, overall survival, duration of response, duration of stable disease, and safety. RESULTS: Thirty-one patients with solid tumors with BRAF mutations were enrolled. Twenty-eight patients were evaluable for efficacy. Patients had tumors with BRAF V600E (n = 26), K601E (n = 2), or other (n = 3) mutations. Two patients with CR (breast and ovarian cancers; V600E), 14 with PR (13 V600E, one N581I), and three with SD16+ (two V600E, one T599_V600insT) were observed with a DC rate of 68% (P < .0001; one-sided 90% CI, 54 to 100) and an OR rate of 57% (95% CI, 37 to 76). Nineteen patients experienced ≥one drug-related grade 3-5 adverse event or serious adverse event including one death attributed to treatment-related kidney injury. CONCLUSION: Cobimetinib plus vemurafenib showed antitumor activity in patients with advanced solid tumors with BRAF V600E mutations; additional study is warranted to confirm the antitumor activity in tumors with non-V600E BRAF mutations.
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Antineoplásicos , Melanoma , Humanos , Vemurafenib/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/genética , Melanoma/tratamento farmacológico , Melanoma/genética , Antineoplásicos/efeitos adversos , MutaçãoRESUMO
BACKGROUND: Most patients with advanced melanomas relapse after checkpoint blockade therapy. Thus, immunotherapies are needed that can be applied safely early, in the adjuvant setting. Seviprotimut-L is a vaccine containing human melanoma antigens, plus alum. To assess the efficacy of seviprotimut-L, the Melanoma Antigen Vaccine Immunotherapy Study (MAVIS) was initiated as a three-part multicenter, double-blind, placebo-controlled phase III trial. Results from part B1 are reported here. METHODS: Patients with AJCC V.7 stage IIB-III cutaneous melanoma after resection were randomized 2:1, with stage stratification (IIB/C, IIIA, IIIB/C), to seviprotimut-L 40 mcg or placebo. Recurrence-free survival (RFS) was the primary endpoint. For an hypothesized HR of 0.625, one-sided alpha of 0.10, and power 80%, target enrollment was 325 patients. RESULTS: For randomized patients (n=347), arms were well-balanced, and treatment-emergent adverse events were similar for seviprotimut-L and placebo. For the primary intent-to-treat endpoint of RFS, the estimated HR was 0.881 (95% CI: 0.629 to 1.233), with stratified logrank p=0.46. However, estimated HRs were not uniform over the stage randomized strata, with HRs (95% CIs) for stages IIB/IIC, IIIA, IIIB/IIIC of 0.67 (95% CI: 0.37 to 1.19), 0.72 (95% CI: 0.35 to 1.50), and 1.19 (95% CI: 0.72 to 1.97), respectively. In the stage IIB/IIC stratum, the effect on RFS was greatest for patients <60 years old (HR=0.324 (95% CI: 0.121 to 0.864)) and those with ulcerated primary melanomas (HR=0.493 (95% CI: 0.255 to 0.952)). CONCLUSIONS: Seviprotimut-L is very well tolerated. Exploratory efficacy model estimation supports further study in stage IIB/IIC patients, especially younger patients and those with ulcerated melanomas. TRIAL REGISTRATION NUMBER: NCT01546571.
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Vacinas Anticâncer/uso terapêutico , Melanoma/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Vacinas Combinadas/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Vacinas Anticâncer/farmacologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vacinas Combinadas/farmacologia , Adulto JovemRESUMO
PURPOSE: Pegylated recombinant human hyaluronidase (PEGPH20) degrades hyaluronan (HA) and, in combination with chemotherapy, prolongs survival in preclinical models. The activity of PEGPH20 with modified fluorouracil, leucovorin, irinotecan, and oxaliplatin (mFOLFIRINOX) was evaluated in patients with metastatic pancreatic cancer (mPC). MATERIALS AND METHODS: Patients had untreated mPC, a performance status of 0 to 1, and adequate organ function. Tumor HA status was not required for eligibility. After a phase Ib dose-finding study of mFOLFIRINOX plus PEGPH20, the phase II open-label study randomly assigned patients (1:1) to the combination arm or to mFOLFIRINOX alone (n = 138). The primary end point was overall survival (OS). RESULTS: PEGPH20 dosages of 3 µg/kg every 2 weeks were more tolerable than twice-weekly dosages used in the phase I study, so 3 µg/kg every 2 weeks was the phase II dosage. An amendment instituted enoxaparin prophylaxis in the PEGPH20 combination arm as a result of increased thromboembolic (TE) events. The planned interim futility analysis when 35 deaths (of 103 analyzable patients) occurred resulted in an OS hazard ratio (HR) of 2.07 that favored the control arm, and the study was closed to accrual. The treatment-related grade 3 to 4 toxicity was significantly increased in the PEGPH20 combination arm relative to control (odds ratio, 2.7; 95% CI, 1.1 to 7.1). The median OS in the mFOLFIRINOX arm was 14.4 months (95% CI, 10.1 to 15.7 months) versus 7.7 months (95% CI, 4.6 to 9.3 months) in the PEGPH20 combination arm. CONCLUSION: Addition of PEGPH20 to mFOLFIRINOX seems to be detrimental in patients unselected for tumor HA status. This combination caused increased toxicity (mostly GI and TE events) and resulted in decreased treatment duration compared with mFOLFIRINOX alone. The median OS in the mFOLFIRINOX control arm (14.4 months) is, to our knowledge, the longest yet reported and can be considered for patients with good PS.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Adenocarcinoma/sangue , Adenocarcinoma/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Relação Dose-Resposta a Droga , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Ácido Hialurônico/sangue , Hialuronoglucosaminidase/administração & dosagem , Hialuronoglucosaminidase/efeitos adversos , Imuno-Histoquímica , Irinotecano/administração & dosagem , Irinotecano/efeitos adversos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Oxaliplatina/administração & dosagem , Oxaliplatina/efeitos adversos , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/patologia , Taxa de SobrevidaRESUMO
PURPOSES: This study aims to describe the clinical course and prognostic factors of patients with small-vessel vasculitis admitted to a medical ICU. METHODS: We reviewed the clinical records of 38 patients with small-vessel vasculitis admitted consecutively to the ICU between January 1997 and May 2004. The APACHE (acute physiology and chronic health evaluation) III prognostic system was used to determine the severity of illness on the first ICU day; the sequential organ failure assessment (SOFA) score was used to measure organ dysfunction, and the Birmingham vasculitis activity score for Wegener granulomatosis (BVAS/WG) was used to assess vasculitis activity. Outcome measures were the 28-day mortality and ICU length of stay. RESULTS: Nineteen patients (50%) had Wegener granulomatosis, 16 patients (42%) had microscopic polyangiitis, 2 patients had CNS vasculitis, and 1 patient had Churg-Strauss syndrome. Reasons for ICU admission included alveolar hemorrhage in 14 patients (37%), sepsis in 5 patients (13%), seizures in 3 patients (8%), and pneumonia in 2 patients (5%). The median ICU length of stay was 4.0 days (interquartile range, 2.0 to 6.0 days). The APACHE III score was lower in survivors than nonsurvivors (p = 0.010). The predicted hospital mortality was 54% for nonsurvivors and 21% for survivors (p = 0.0038). The mean SOFA score was 11.6 (SD, 2.6) in nonsurvivors, compared to 6.9 (SD, 2.4) in survivors (p = 0.0004). Mean BVAS/WG scores were 8.6 (SD, 3.6) in nonsurvivors and 4.7 (SD, 4.6) in survivors (p = 0.0889). Twenty-six percent of the patients received invasive mechanical ventilation, and 33% underwent dialysis. The 28-day and 1-year mortality rates were 11% and 29%, respectively. CONCLUSIONS: The mortality of patients with small-vessel vasculitis admitted to the ICU is lower than predicted, and alveolar hemorrhage is the most common reason for ICU admission.
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Síndrome de Churg-Strauss/diagnóstico , Granulomatose com Poliangiite/diagnóstico , Hemoptise/etiologia , Poliarterite Nodosa/diagnóstico , Vasculite do Sistema Nervoso Central/diagnóstico , Idoso , Biópsia , Síndrome de Churg-Strauss/complicações , Síndrome de Churg-Strauss/mortalidade , Feminino , Seguimentos , Granulomatose com Poliangiite/complicações , Granulomatose com Poliangiite/mortalidade , Hemoptise/diagnóstico , Hemoptise/mortalidade , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva , Tempo de Internação , Masculino , Minnesota/epidemiologia , Poliarterite Nodosa/complicações , Poliarterite Nodosa/mortalidade , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença , Vasculite do Sistema Nervoso Central/complicações , Vasculite do Sistema Nervoso Central/mortalidadeRESUMO
Severe sepsis may be associated with depression of myocardial function, attributed to various inflammatory mediators. Myocardial dysfunction in sepsis is characterized by biventricular failure and complicates usual therapy with high-volume fluid resuscitation and vasopressors. However, in patients who survive septic shock, myocardial dysfunction can improve rapidly. We describe a young woman with septic shock due to Streptococcus pneumoniae, complicated by severe but reversible biventricular dysfunction.
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Cardiomiopatia Dilatada/complicações , Infecções Pneumocócicas/complicações , Sepse/complicações , Adulto , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/fisiopatologia , Diagnóstico Diferencial , Ecocardiografia , Feminino , Seguimentos , Ventrículos do Coração/fisiopatologia , Humanos , Infecções Pneumocócicas/diagnóstico , Infecções Pneumocócicas/microbiologia , Radiografia Torácica , Sepse/diagnóstico , Sepse/microbiologia , Streptococcus pneumoniae/isolamento & purificação , Volume SistólicoRESUMO
AIM: This study elicited oncologists' insights into published statistics that 20% of cancer patients receive chemotherapy within 2 weeks of death and that the median survival between chemotherapy administration and death is 37 days. SUBJECTS AND METHODS: A semiqualitative survey was developed to enable respondents to provide anonymous, write-in comments on the statistics above. This survey was sent electronically on two separate occasions to oncologists in the upper midwestern United States. Qualitative methods were used to analyze data. RESULTS: A total of 422 oncology health-care providers were sent the survey, and 61 responded. Nine themes emerged: 1) these decisions are strongly patient-driven; 2) newer agents are driving the decision to continue with cancer treatment; 3) financial incentives on the part of the medical community explain these high rates; 4) health-care reform is necessary; 5) even a small chance of patient benefit justifies this practice; 6) this practice is detrimental to patients because it precludes the initiation of hospice services; 7) others may be prescribing in this manner, but "not us"; 8) these issues are complicated, revolve around society values, and the oncologist alone cannot claim responsibility for such high rates of chemotherapy administration; and 9) there exist barriers to end-of-life discussions. CONCLUSION: Many oncologists are in fact reluctant to prescribe chemotherapy at the end of life, and the complexity of this topic underscores the potential for oncologists and palliative care providers to collaborate in an effort to provide cancer patients the best care at the very end of life.
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Antineoplásicos/administração & dosagem , Atitude do Pessoal de Saúde , Oncologia/métodos , Neoplasias/tratamento farmacológico , Cuidados Paliativos/métodos , Assistência Terminal/métodos , Adulto , Antineoplásicos/economia , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Masculino , Futilidade Médica , Oncologia/economia , Oncologia/normas , Pessoa de Meia-Idade , Meio-Oeste dos Estados Unidos , Neoplasias/economia , Cuidados Paliativos/normas , Preferência do Paciente , Pesquisa Qualitativa , Assistência Terminal/economia , Assistência Terminal/normasRESUMO
Oncologic emergencies represent a wide variety of conditions that can occur at any time during the course of a malignancy, from an initial presenting manifestation in someone with an undiagnosed cancer, to end-stage incurable metastatic disease. Emergent conditions can also arise after a malignancy has been in remission for many years, even decades, so clinicians must be aware of any prior history of cancer in patients. Oncologic emergencies include conditions caused by the cancer itself or side effects of therapy. Emergent conditions include metabolic, cardiac, neurologic, or infectious disorders. Many of these emergencies are imminently life-threatening, and can occur in patients with curable disease (such as lymphomas or leukemias); however, many also present in patients with incurable advanced disease. Prompt recognition and treatment of these conditions can lead to markedly improved quality and quantity of life.
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Emergências , Neoplasias/complicações , Tratamento de Emergência , Humanos , Metástase Neoplásica , Neoplasias/fisiopatologiaRESUMO
OBJECTIVES: This study was performed to evaluate the addition of temozolomide (TMZ) to whole brain radiotherapy (WBRT) for brain metastases from melanoma. METHODS: Seven patients with brain metastases from melanoma were treated on a North Central Cancer Treatment Group (NCCTG) trial (N0274) of TMZ plus WBRT. TMZ was given orally in doses of 200 mg/m² for 5 days every 4 weeks for up to 8 cycles. WBRT was started on the first day of TMZ and included the delivery of 3750 cGy in 15 fractions. In addition, separately analyzed was a cohort of 53 patients treated at the Mayo Clinic who received WBRT alone (39 patients) or WBRT plus TMZ (14 patients). RESULTS: The median survival of the 7 patients treated on N0274 was 3.6 months with 2 of 7 (29%) failing in brain and 5 of 7 (71%) failing elsewhere. For the other cohort of 53 patients, the median survival was 3.8 months with WBRT alone compared 4.3 months for WBRT plus TMZ (P = 0.5). CONCLUSIONS: Patients did not appear to benefit from the addition of TMZ to WBRT for the treatment of their brain metastases. Further improvements in outcome will require research to discover more effective systemic therapy and RT techniques.
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Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/terapia , Irradiação Craniana/métodos , Dacarbazina/análogos & derivados , Melanoma/secundário , Melanoma/terapia , Neoplasias Cutâneas/patologia , Administração Oral , Idoso , Antineoplásicos/administração & dosagem , Neoplasias Encefálicas/mortalidade , Estudos de Coortes , Terapia Combinada , Dacarbazina/administração & dosagem , Esquema de Medicação , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Melanoma/mortalidade , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Estudos Retrospectivos , Medição de Risco , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/terapia , Análise de Sobrevida , Temozolomida , Resultado do TratamentoAssuntos
Adenoma/complicações , Hiperparatireoidismo/diagnóstico , Pancreatite Necrosante Aguda/etiologia , Neoplasias das Paratireoides/complicações , Adenoma/diagnóstico por imagem , Adenoma/cirurgia , Idoso , Drenagem/métodos , Febre/etiologia , Humanos , Hiperparatireoidismo/diagnóstico por imagem , Hiperparatireoidismo/etiologia , Hiperparatireoidismo/cirurgia , Masculino , Pancreatite Necrosante Aguda/diagnóstico por imagem , Pancreatite Necrosante Aguda/terapia , Neoplasias das Paratireoides/diagnóstico por imagem , Neoplasias das Paratireoides/cirurgia , Paratireoidectomia , Cintilografia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Vômito/etiologiaRESUMO
The majority of patients with advanced cancer suffers from loss of appetite and loss of weight at some point during their disease course. This sign and this symptom herald an early demise. However, no therapeutic intervention, apart from effective antineoplastic therapy, has been able to reverse this syndrome totally, and, in turn, to reverse this prognostic effect. Most clinical trials have focused largely on palliating symptoms, and, to this end, progestational agents and corticosteroids have proven to be the most effective in terms of improving appetite. This article reviews data to support the use of these agents, discusses the findings of other more recent studies in this field and provides an overview of promising strategies that merit further investigation.
Assuntos
Anorexia/tratamento farmacológico , Estimulantes do Apetite/uso terapêutico , Glucocorticoides/uso terapêutico , Progestinas/uso terapêutico , Anorexia/etiologia , Antineoplásicos/uso terapêutico , Apetite/efeitos dos fármacos , Estimulantes do Apetite/efeitos adversos , Estimulantes do Apetite/farmacologia , Glucocorticoides/efeitos adversos , Glucocorticoides/farmacologia , Humanos , Neoplasias/complicações , Progestinas/efeitos adversos , Progestinas/farmacologia , Prognóstico , Redução de Peso/efeitos dos fármacosRESUMO
The immunologic mechanisms of action of rituximab include complement mediated lysis and antibody-dependent cellular cytotoxicity. We hypothesised that a stronger host immune system prior to rituximab therapy for follicular (grades 1and 2) lymphomas (FL) would result in better response rates and longer time to progression (TTP). Thus, we studied the role of absolute lymphocyte count (ALC) prior to rituximab therapy on treatment efficacy and TTP in FL patients. Between 1996 and 2002, 79 FL patients were treated with single agent rituximab during their lymphoma treatment at the Mayo Clinic. The median age of the cohort was 56.6 years (range: 25-98 years). The median TTP was 12.5 months (range: 1-76 months). Superior TTP was observed with an ALC > or =0.89 x 10(9)/l (n = 40) compared with an ALC <0.89 x 10(9)/l (n = 39) at the time of rituximab therapy (median: 36.5 vs. 8.1 months, respectively, P < 0.0009). Higher complete response rates were observed in the ALC > or =0.89 x 10(9)/l (23/40, 58%) compared with the ALC <0.89 x 10(9)/l (5/39, 13%) (P < 0.0001). Multivariate analysis showed ALC to be an independent predictor for TTP. This study supports our hypothesis that a higher ALC predicts longer TTP following rituximab therapy.