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1.
Anticancer Res ; 39(11): 6347-6353, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704866

RESUMO

BACKGROUND/AIM: The aim of this study was to determine the significance of immunonutritional and physical index in the assessment of risk associated with pancreaticoduodenectomy (PD) in the elderly. PATIENTS AND METHODS: This study enrolled 92 patients who underwent PD. They were divided into 2 groups: Group A included patients 79 years and younger (n=79) and Group B patients 80 years and older (n=13). Among 37 patients, physical function and body composition were also evaluated. RESULTS: Significantly higher neutrophil-lymphocyte ratio, lower prognostic nutritional index (PNI), and controlling nutritional score were observed in Group B. Muscle strength and walking ability were significantly impaired in Group B, although there was no significant difference in body composition. Age was not correlated with the incidence of postoperative complications, overall survival or recurrence-free survival by univariate and multivariate analysis. CONCLUSION: PD is justified for the elderly, with acceptable morbidity and prognosis. However, immunonutritional status and physical function are significantly impaired; thus, appropriate case selection and active nutritional support are required for the elderly.


Assuntos
Limitação da Mobilidade , Força Muscular , Estado Nutricional , Pancreaticoduodenectomia/efeitos adversos , Complicações Pós-Operatórias , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Neoplasias dos Ductos Biliares/cirurgia , Composição Corporal , Comorbidade , Neoplasias Duodenais/cirurgia , Feminino , Humanos , Contagem de Leucócitos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos/citologia , Avaliação Nutricional , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/mortalidade , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Medição de Risco , Albumina Sérica/análise
2.
Jpn J Clin Oncol ; 49(12): 1114-1119, 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31723978

RESUMO

OBJECTIVE: The aim of this survey was to describe how geriatric oncology is integrated in undergraduate teaching and graduate training as well as in daily clinical oncology practice in Japan. METHODS: All schools of medicine in Japan are allied with graduate schools of medicine. We conducted a survey of all Japanese medical and graduate schools (n = 81), and designated cancer hospitals (n = 437) from July 2018 to August 2018. The survey of the schools asked about existence of geriatrics division and geriatric oncology service and if an education curriculum in geriatrics and geriatric oncology was used. The survey of designated cancer hospitals requested general hospital information and the current practice patterns of general geriatric and cancer patients. RESULTS: Forty-eight medical schools (59%) participated in this survey, and teaching in geriatrics and geriatric oncology was implemented in 23 schools and 1 school, respectively. Forty-two graduate schools of medicine (52%) responded; five had an education curriculum in geriatrics, but none provided geriatric oncology training. Among 151 participating hospitals (35%), 5 had a geriatrics division and 20 hospitals employed geriatricians. There was no geriatric oncology service or geriatric oncology specialists in any of the 151 hospitals. Seventy percent of the hospitals reported performing a geriatric assessment for at least some older adults with cancer. CONCLUSIONS: This survey provides information on the current state of Japanese education and clinical practice in geriatric oncology. In Japan, a nation with among the largest population of older citizens in the world, education and training greatly need to be promoted to disseminate a core set of geriatrics knowledge and skills to students, trainees and healthcare professionals.

3.
Oncologist ; 24(7): e565-e573, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30552160

RESUMO

BACKGROUND: The aim of this meta-analysis was to compare patient-reported outcomes (PROs) between programmed death receptor-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors and standard-of-care therapy in patients with advanced cancer. METHODS: We searched randomized controlled trials (RCTs) comparing single-agent PD-1/PD-L1 inhibitors (nivolumab, pembrolizumab, atezolizumab, avelumab, or durvalumab) with standard-of-care therapy in patients with advanced cancer reporting PROs with generic measures: the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 items (QLQ-C30) and the EuroQol Five Dimensions Questionnaire. The summary outcomes were changes in PROs from baseline to follow-up within and between treatment groups and time to deterioration (TTD) in PROs based on clinically meaningful change. RESULTS: A total of 6,334 patients from 13 RCTs were included: six nivolumab, five pembrolizumab, and two atezolizumab trials. For the QLQ-C30 global health status/quality of life, the pooled difference in mean change between treatment groups was 5.1 (95% confidence interval [CI], 3.3-6.9; p < .001) favoring PD-1/PD-L1 inhibitors. The pooled mean change from baseline in PD-1/PD-L1 inhibitors and controls was 0.1 (95% CI, -2.2, 2.5) and - 6.1 (95% CI, -8.4, -3.8), respectively. The TTD was significantly longer with PD-1/PD-L1 inhibitors, with a hazard ratio of 0.72 (95% CI, 0.55-0.93; p = .011). Similarly, significantly better outcomes were noted with PD-1/PD-L1 inhibitors on most of the other PRO measures. CONCLUSION: PD1/PD-L1 inhibitors maintained health-related quality of life to a greater degree and had less worsening in symptoms than standard-of-care therapy even though patients on these immune modulators were on treatment longer. The better PRO profile further supports the clinical benefit of this treatment strategy for advanced cancer. IMPLICATIONS FOR PRACTICE: We conducted a systematic review and meta-analysis to compare patient-reported outcomes (PROs) of programmed death receptor-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors and standard-of-care therapy in patients with advanced cancer. PD-1/PD-L1 inhibitors were associated with consistently smaller PRO score deterioration from baseline to follow-up for different health-related quality-of-life and symptoms scales. In addition, the time to deterioration in multiple PRO domains was significantly longer with PD-1/PD-L1 inhibitors. Taken together, these findings indicate that the patients treated with PD-1/PD-L1 inhibitors maintained health-related quality of life to a greater degree and had less symptom burden compared with those treated with standard-of-care therapy.

4.
J Geriatr Oncol ; 10(2): 279-284, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30131235

RESUMO

BACKGROUND: Our aim was to evaluate the prognostic impact of three inflammatory markers - neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR) and lymphocyte monocyte ratio (LMR) - on overall survival (OS) in older adults with cancer. MATERIALS AND METHODS: Our sample includes 144 patients age ≥ 65 years with solid tumor cancer who completed a cancer-specific Geriatric Assessment (GA) from 2010 to 2014 and had pretreatment CBC with differential. NLR was dichotomized a previously reported cut-off value of 3.5, while PLR and LMR were dichotomized at the median. Cox proportional hazards models evaluated whether NLR, PLR and LMR were predictive of OS independent of covariates including a recently developed 3-item GA-derived prognostic scale consisting of (1) "limitation in walking several blocks", (2) "limitation in shopping", and (3) "≥ 5% unintentional weight loss in 6 months". RESULTS: Median age was 72 years, 53% had breast cancer, 27% had stage 4 cancer, 14% had Karnofsky Performance Status (KPS) < 80, 11% received less intensive than standard treatment for stage, and 39% had NLR > 3.5. In univariable analysis, higher NLR and PLR and lower LMR were significantly associated with worse OS. NLR remained a significant predictor of OS (HR = 2.16, 95% CI; 1.10-4.25, p = .025) after adjusting for cancer type, stage, age, KPS, treatment intensity, and the GA-derived prognostic scale. CONCLUSION: NLR > 3.5 is predictive of poorer OS in older adults with cancer, independent of traditional prognostic factors and the GA-derived prognostic scale.

6.
J Geriatr Oncol ; 9(4): 329-336, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29426572

RESUMO

OBJECTIVE: A geriatric assessment (GA) assesses functional age of older patients with cancer and is a well-established tool predictive of toxicity and survival. The objective of this study was to investigate the prognostic value of individual GA items. MATERIALS AND METHODS: 546 patients with cancer ≥ 65 years completed GA from 2009 to 2014 and were followed for survival status for a median of 3.7 years. The GA consisted of function, nutrition, comorbidity, cognition, psychological state, and social activity/support domains. GA items with p < 0.05 in univariable analyses for overall survival (OS) were entered into multivariable stepwise selection procedure using a Cox proportional hazards model. A prognostic scale was constructed with significant GA items retained in the final model. RESULTS: Median age was 72 years, 49% had breast cancer, and 42% had stage 3-4 cancer. Three GA items were significant prognostic factors, independent of traditional factors (cancer type, stage, age, and Karnofsky Performance Status): (1) "limitation in walking several blocks", (2) "limitation in shopping", and (3) "≥ 5% unintentional weight loss in 6 months". A three-item prognostic scale was constructed with these items. In comparison with score 0 (no positive items), hazard ratios for OS were 1.85 for score 1, 2.97 for score 2, and 8.67 for score 3. This translated to 2-year estimated survivals of 85%, 67%, 51% and 17% for scores of 0, 1, 2 and 3, respectively. CONCLUSIONS: This three-item scale was a strong independent predictor of survival. If externally validated, this could be a streamlined tool with broader applicability.


Assuntos
Avaliação Geriátrica/métodos , Avaliação de Estado de Karnofsky , Neoplasias/mortalidade , Atividades Cotidianas/classificação , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Avaliação Geriátrica/estatística & dados numéricos , Humanos , Masculino , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Análise de Sobrevida
7.
Oncologist ; 23(5): 573-579, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29371477

RESUMO

BACKGROUND: The decision whether to treat older adults with advanced cancer with standard therapy (ST) or reduced therapy (RT) is complicated by heterogeneity in aging. We assessed the potential utility of the chemotherapy toxicity risk score (CTRS) [J Clin Oncol 2011;29:3457-3465] for treatment decisions in older adults. MATERIALS AND METHODS: This was a prospective observational study of patients aged ≥65 years receiving first-line chemotherapy for advanced cancer for which combination chemotherapy is the standard of care. Patients were categorized as high risk (CTRS ≥10), for whom RT (dose-reduced combination or single-agent chemotherapy) is deemed appropriate, or nonhigh risk (CTRS <10), for whom ST is deemed appropriate for toxicity. The primary objective was to estimate the agreement in chemotherapy choice (ST vs. RT) between the treating physician and the CTRS using a κ statistic. RESULTS: Fifty-eight patients (median age, 71 years) were enrolled. Thirty-eight patients received ST (21 had CTRS <10, and 17 had CTRS ≥10), and 20 patients received RT (12 had CTRS ≥10, and 8 had CTRS <10), with minimal agreement in chemotherapy choice (κ = 0.14; 95% CI, -0.10 to 0.38). Grade 3-4 toxicity and hospitalization occurred in 60% and 27% of 55 patients with follow-up data, respectively. Among patients receiving ST, patients with CTRS ≥10 had a higher incidence of toxicity (88% vs. 40%, p = .006) and hospitalization (50% vs. 15%, p = .03) than those with CTRS <10. CONCLUSION: Older patients with cancer with a high CTRS who receive combination chemotherapy have an exceedingly high rate of severe toxicity and hospitalization. IMPLICATIONS FOR PRACTICE: The potential utility of the chemotherapy toxicity risk score (CTRS) in old adults with advanced solid tumors receiving first-line chemotherapy was assessed. Little agreement was found between chemotherapy treatment decisions based on the clinical impression versus what was recommended based on the CTRS. Among patients treated with standard-dose combination chemotherapy, patients with CTRS ≥10 had a very high incidence of grade 3-4 toxicities and hospitalization, which was significantly greater than that of patients with a low CTRS (<10). These findings suggest that the addition of CTRS to the clinical impression has a potential to improve treatment decisions.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Masculino , Neoplasias/patologia , Estudos Prospectivos
8.
Oncologist ; 22(5): 609-619, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28438887

RESUMO

INTRODUCTION: Cisplatin, a platinum-based antineoplastic agent, is the cornerstone for the treatment of many malignancies. Nephrotoxicity is the primary dose-limiting toxicity, and various hydration regimens and supplementation strategies are used to prevent cisplatin-induced kidney injury. However, evidence-based recommendations on specific hydration regimens are limited. A systematic review was performed to evaluate clinical studies that have examined hydration and supplementation strategies to prevent cisplatin-induced nephrotoxicity. MATERIALS AND METHODS: PubMed and Excerpta Medica databases were searched from 1966 through October 2015 for clinical trials and other studies focused on hydration regimens to prevent nephrotoxicity in cancer patients treated with cisplatin. The University of Oxford Centre for Evidence-Based Medicine criteria were used to grade level of evidence. RESULTS: Among the 1,407 identified studies, 24 were included in this systematic review. All studies differed on type, volume, and duration of hydration. Among the 24 studies, 5 evaluated short-duration hydration, 4 evaluated low-volume hydration, 4 investigated magnesium supplementation, and 7 reviewed forced diuresis with hydration. Short-duration and lower-volume hydration regimens are effective in preventing cisplatin-induced nephrotoxicity. Magnesium supplementation may have a role as a nephroprotectant, and forced diuresis may be appropriate in some patients receiving cisplatin. CONCLUSION: Hydration is essential for all patients to prevent cisplatin-induced nephrotoxicity. Specifically, short-duration, low-volume, outpatient hydration with magnesium supplementation and mannitol forced diuresis (in select patients) represent best practice principles for the safe use of cisplatin. The Oncologist 2017;22:609-619 IMPLICATIONS FOR PRACTICE: The findings contained within this systematic review show that (a) hydration is essential for all patients to prevent cisplatin-induced nephrotoxicity, (b) short-duration, low-volume, outpatient hydration regimens appear to be safe and feasible, even in patients receiving intermediate- to high-dose cisplatin, (c) magnesium supplementation (8-16 milliequivalents) may limit cisplatin-induced nephrotoxicity, and (d) mannitol may be considered for high-dose cisplatin and/or patients with preexisting hypertension. These findings have broad implications for clinical practice and represent best practice principles for the prevention of cisplatin-induced nephrotoxicity.


Assuntos
Antineoplásicos/uso terapêutico , Cisplatino/uso terapêutico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Neoplasias/tratamento farmacológico , Antineoplásicos/efeitos adversos , Cisplatino/efeitos adversos , Relação Dose-Resposta a Droga , Medicina Baseada em Evidências , Feminino , Humanos , Rim/efeitos dos fármacos , Masculino , Neoplasias/complicações , Neoplasias/patologia
9.
Oncologist ; 22(4): 470-479, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28275115

RESUMO

BACKGROUND: Compared with chemotherapy, significant improvement in survival outcomes with the programmed death receptor-1 (PD-1) inhibitors nivolumab and pembrolizumab and the programmed death-ligand 1 (PD-L1) inhibitor atezolizumab has been shown in several types of advanced solid tumors. We conducted a systematic review and meta-analysis to compare safety and tolerability between PD-1/PD-L1 inhibitors and chemotherapy. METHODS: PubMed and American Society of Clinical Oncology (ASCO) databases were searched 1966 to September 2016. Eligible studies included randomized controlled trials (RCTs) comparing single-agent U.S. Food and Drug Administration-approved PD-1/PD-L1 inhibitors (nivolumab, pembrolizumab, or atezolizumab) with chemotherapy in cancer patients reporting any all-grade (1-4) or high-grade (3-4) adverse events (AEs), all- or high-grade treatment-related symptoms, hematologic toxicities and immune-related AEs, treatment discontinuation due to toxicities, or treatment-related deaths. The summary incidence, relative risk, and 95% confidence intervals were calculated. RESULTS: A total of 3,450 patients from 7 RCTs were included in the meta-analysis: 4 nivolumab, 2 pembrolizumab, and 1 atezolizumab trials. The underlying malignancies included were non-small cell lung cancer (4 trials) and melanoma (3 trials). Compared with chemotherapy, the PD-1/PD-L1 inhibitors had a significantly lower risk of all- and high-grade fatigue, sensory neuropathy, diarrhea and hematologic toxicities, all-grade anorexia, nausea, and constipation, any all- and high-grade AEs, and treatment discontinuation. There was an increased risk of all-grade rash, pruritus, colitis, aminotransferase elevations, hypothyroidism, and hyperthyroidism, and all- and high-grade pneumonitis with PD1/PD-L1 inhibitors. CONCLUSION: PD-1/PD-L1 inhibitors are overall better tolerated than chemotherapy. Our results provide further evidence supporting the favorable risk/benefit ratio for PD-1/PD-L1 inhibitors. The Oncologist 2017;22:470-479 IMPLICATIONS FOR PRACTICE: We conducted a systematic review and meta-analysis to compare summary toxicity endpoints and clinically relevant adverse events between programmed death receptor-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors and chemotherapy. PD1/PD-L1 inhibitors were associated with a lower risk of treatment-related symptoms (fatigue, anorexia, nausea, diarrhea, constipation, and sensory neuropathy) but a higher risk of immune-related adverse events (AEs). Summary toxicity endpoints favor PD1/PD-L1 inhibitors (any all- and high-grade AEs and treatment discontinuation). PD1/PD-L1 inhibitors are overall better tolerated than chemotherapy. In addition to efficacy data from trials, our findings provide useful information for clinicians for well-balanced discussions with their patients on the risks and benefits of treatment options for advanced cancer.


Assuntos
Antígeno B7-H1/antagonistas & inibidores , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Melanoma/tratamento farmacológico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Antígeno B7-H1/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Intervalo Livre de Doença , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/classificação , Humanos , Melanoma/genética , Melanoma/patologia , Nivolumabe , Receptor de Morte Celular Programada 1/genética
10.
Aging (Albany NY) ; 9(3): 650-664, 2017 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-28273043

RESUMO

We examined the associations between frailty and inflammatory markers, in particular neutrophil lymphocyte ratio (NLR), in elderly cancer patients. We conducted cross-sectional analyses of data derived from the Carolina Seniors Registry (CSR), a database of geriatric assessments (GA) in older adults (≧65 years) with cancer. We included patients in the CSR who had a GA and complete blood count test before initiation of therapy. The primary outcome was frailty, determined using the 36-item Carolina Frailty Index (CFI). In our sample of 133 patients, the median age was 74, and 54% were robust, 22% were pre-frail, and 24% were frail. There was a significant positive correlation between CFI and NLR (r = 0.22, p = 0.025). In multivariable analysis, patients in the top tertile of NLR had an odds ratio of 3.8 (95% CI = 1.1-12.8) for frail/pre-frail status, adjusting for age, sex, race, education level, marital status, cancer type and stage. In bivariable analyses, higher NLR was associated with lower instrumental activity of daily living (IADL) score (p = 0.040) and prolonged timed up and go (p = 0.016). This study suggests an association between frailty and inflammation in older adults with cancer.


Assuntos
Biomarcadores Tumorais/sangue , Idoso Fragilizado , Inflamação , Neoplasias , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Avaliação Geriátrica/métodos , Humanos , Contagem de Linfócitos , Masculino , Neutrófilos
11.
Clin Cancer Res ; 23(3): 658-665, 2017 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-27489287

RESUMO

PURPOSE: Severe skeletal muscle (SM) loss (sarcopenia) is associated with poor cancer outcomes, including reduced survival and increased toxicity. This study investigates SM measures in metastatic breast cancer (MBC) patients receiving first-line taxane-based chemotherapy and evaluates associations with treatment toxicity and other outcomes. EXPERIMENTAL DESIGN: Using computerized tomography (CT) images taken for the evaluation of disease burden, skeletal muscle area (SMA), and density (SMD) were measured at the third lumbar vertebrae. Sarcopenia was defined as skeletal muscle index (SMI = SMA/height2) ≤ 41. Skeletal muscle gauge (SMG) was created by multiplying SMI × SMD. Fisher exact tests, t tests, the Kaplan-Meier method, and Cox regression modeling were used. RESULTS: MBC patients (N = 40), median age 55 (range, 34-80), 58% sarcopenic, median SMG 1296 AU (SD, 522). Grade 3-4 toxicity was found in 57% of sarcopenic versus 18% of non-sarcopenic patients (P = 0.02). Toxicity-related hospitalizations were also higher in sarcopenic patients (39% vs. 0%, P = 0.005) as were any adverse events-defined as any grade 3-4 toxicities, hospitalizations, dose reductions, or dose delay-(74% vs. 35%, P = 0.02). Low SMG was associated with grade 3-4 toxicity (P = 0.04), hospitalization (P = 0.01), and time to treatment failure (for progression or toxicity; P = 0.03). Low SMG had a borderline significant association with any adverse event (P = 0.06) and overall survival (P = 0.07). CONCLUSIONS: SM measures are associated with toxicity outcomes and survival in MBC patients receiving first-line taxane-based chemotherapy. Further studies are needed to explore how routinely obtained CT scans can be used to individualize dosing and improve treatment planning. Clin Cancer Res; 23(3); 658-65. ©2016 AACR.


Assuntos
Adenocarcinoma/secundário , Antineoplásicos Fitogênicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Composição Corporal , Neoplasias da Mama/tratamento farmacológico , Hospitalização/estatística & dados numéricos , Músculo Esquelético/diagnóstico por imagem , Sarcopenia/diagnóstico por imagem , Taxoides/efeitos adversos , Tomografia Computadorizada por Raios X , Adenocarcinoma/complicações , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Fitogênicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Índice de Massa Corporal , Superfície Corporal , Neoplasias da Mama/complicações , Neoplasias da Mama/mortalidade , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Músculo Esquelético/patologia , Tamanho do Órgão , Prognóstico , Modelos de Riscos Proporcionais , Sarcopenia/induzido quimicamente , Sarcopenia/etiologia , Gravidade Específica , Taxoides/administração & dosagem
12.
Cancer Treat Rev ; 45: 30-7, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26946217

RESUMO

BACKGROUND: Immune checkpoint inhibitors (ICIs) rely on the presence of ongoing immune response to exert their antitumor effect. Little is known whether an age-related decline in immune function negatively influences antitumor response and in so doing diminishes the efficacy of ICIs in elderly subjects. We performed a meta-analysis to compare the efficacy of ICIs between younger and older patients. PATIENTS AND METHODS: PubMed and the ASCO databases were searched up to September 2015. We included randomized controlled trials (RCTs) of ICIs (ipilimumab, tremelimumab, nivolumab and pembrolizumab) reporting subgroup comparison of overall survival (OS) and/or progression-free survival (PFS) based on age cutoffs. The summary hazard ratio (HR) and 95% confidence interval (CI) were calculated. RESULTS: A total of 5265 patients from nine RCTs of ICI were included. When patients are dichotomized into younger and older groups with an age cut-off of 65-70 years, ICIs improved OS in both younger (HR, 0.75; 95% CI, 0.68-0.82) and older (HR, 0.73; 95% CI, 0.62-0.87) groups. An improvement in PFS was observed in younger (HR, 0.58; 95% CI, 0.40-0.84) and older (HR, 0.77; 95% CI, 0.58-1.01) patients. Subgroup analyses according to ICI and tumor type showed a consistent survival benefit in both younger and older groups except for the subgroup of older patients treated in 4 trials of anti-programmed cell death protein-1 (PD-1) monoclonal antibody (HR, 0.86; 95% CI, 0.41-1.83). CONCLUSIONS: A benefit in OS with ICIs was significant in both younger and older patients with a cut-off age of 65-70 years.


Assuntos
Envelhecimento/imunologia , Anticorpos Monoclonais , Neoplasias , Fatores Etários , Anticorpos Monoclonais/classificação , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/farmacologia , Antineoplásicos/classificação , Antineoplásicos/imunologia , Antineoplásicos/farmacologia , Intervalo Livre de Doença , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
13.
Breast Cancer Res Treat ; 156(2): 227-36, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26988358

RESUMO

Capecitabine 1000 mg/m(2) bid × 14 days every 21 days (14/21) has been reported to have similar efficacy but more favorable toxicity profile than the approved dosage of 1250 mg/m(2). However, a dose-toxicity relationship of capecitabine in breast cancer patients has not been fully elucidated. We performed a systematic review and meta-analysis to compare a safety profile between capecitabine starting dose of 1000 and 1250 mg/m(2) bid. Studies were identified using PubMed, ASCO, and San Antonio Breast Cancer Symposium abstract databases through December 2015. Eligible trials included phase II/III trials of capecitabine monotherapy at 1000 or 1250 mg/m(2) bid (14/21) for breast cancer patients that reported adequate safety data for all (grade 1-4) or high (grade 3-4) grade hand foot syndrome (HFS), diarrhea, fatigue, nausea, vomiting, stomatitis, neutropenia, thrombocytopenia, or anemia, as well as dose reductions, treatment discontinuation or treatment-related deaths. The summary incidence was calculated using random-effects models. A total of 4833 patients from 34 trials were included. 1218 and 3615 patients were treated with capecitabine 1000 and 1250 mg/m(2) bid, respectively. A significantly lower incidence of dose reduction (15.9 vs. 39.0 %; P = 0.007), high-grade HFS (12.0 vs. 19.0 %; P = 0.01), diarrhea (5.3 vs. 9.1 %; P = 0.01), and neutropenia (1.8 vs. 7.3 %; P < 0.01), and all-grade neutropenia (5.8 vs. 25.4 %; P = 0.01) was seen in capecitabine 1000 mg/m(2) compared to 1250 mg/m(2). Capecitabine monotherapy at 1000 mg/m(2) bid (14/21) has a clinically meaningful and significantly better toxicity profile compared to 1250 mg/m(2) bid (14/21).


Assuntos
Antimetabólitos Antineoplásicos/toxicidade , Neoplasias da Mama/tratamento farmacológico , Capecitabina/toxicidade , Síndrome Mão-Pé/etiologia , Estomatite/induzido quimicamente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/administração & dosagem , Capecitabina/administração & dosagem , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Relação Dose-Resposta a Droga , Feminino , Humanos , Distribuição Aleatória , Resultado do Tratamento
14.
Eur J Cancer ; 57: 58-67, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26882087

RESUMO

BACKGROUND: Body composition plays an important role in predicting treatment outcomes in adults with cancer. Using existing computed tomographic (CT) cross-sectional imaging and readily available software, the assessment of skeletal muscle mass to evaluate sarcopenia has become simplified. We performed a systematic review and meta-analysis to quantify the prognostic value of skeletal muscle index (SMI) obtained from cross-sectional CT imaging on clinical outcomes in non-haematologic solid tumours. METHODS: We searched PubMed and the American Society Clinical Oncology online database of meeting abstracts up to October 2015 for relevant studies. We included studies assessing the prognostic impact of pre-treatment SMI on clinical outcomes in patients with non-haematologic solid tumours. The primary outcome was overall survival (OS) and the secondary outcomes included cancer-specific survival (CSS), disease-free survival (DFS), and progression-free survival (PFS). The summary hazard ratio (HR) and 95% confidence interval (CI) were calculated. RESULTS: A total of 7843 patients from 38 studies were included. SMI lower than the cut-off was associated with poor OS (HR = 1.44, 95% CI = 1.32-1.56, p < 0.001). The effect of SMI on OS was observed among various tumour types and across disease stages. Worse CSS was also associated with low SMI (HR = 1.93, 95% CI = 1.38-2.70, p < 0.001) as well as DFS (HR = 1.16, 95% CI = 1.00-1.30, p = 0.014), but not PFS (HR = 1.54, 95% CI = 0.90-2.64, p = 0.117). CONCLUSIONS: This meta-analysis demonstrates that low SMI at cancer diagnosis is associated with worse survival in patients with solid tumours. Further research into understanding and mitigating the negative effects of sarcopenia in adults with cancer is needed.


Assuntos
Neoplasias/mortalidade , Sarcopenia/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Sarcopenia/etiologia , Adulto Jovem
16.
Cancer Treat Rev ; 41(10): 971-8, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26481060

RESUMO

BACKGROUND: The immune system plays an important role in cancer pathogenesis. A low lymphocyte-to-monocyte ratio (LMR), as a simple biomarker of host immune system, has been suggested to be related to poor prognosis in various cancers. We performed a systematic review and meta-analysis to quantify the prognostic value of LMR on clinical outcomes in non-hematologic solid tumors. PATIENTS AND METHODS: We searched PubMed and the ASCO online database of meeting abstracts up to July 2015 for relevant studies. We included studies assessing the prognostic impact of pre-treatment LMR on clinical outcomes in patients with non-hematologic solid tumors. The primary outcome was overall survival (OS) and the secondary outcomes were cancer-specific survival (CSS) and disease-free survival (DFS). The summary hazard ratio (HR) and 95% confidence interval (CI) were calculated. RESULTS: A total of 11,197 patients from 29 studies were included. LMR lower than the cut-off was associated with poor OS (HR, 1.73; 95% CI, 1.55-1.93; P<0.001), CCS (HR, 1.56; 95% CI, 1.27-1.91; P<0.001) and DFS (HR, 1.56; 95% CI, 1.31-1.86; P<0.001). The effect of LMR on OS was observed in among various tumor types and across disease stages. The median cut-off value for LMR was 3.0 (range=2.0-5.3). Subgroup analysis according to cut-off value (<3.0, 3.0 to <4.0, 4.0 to <5.0, and ≧5.0) showed a significant prognostic value of LMR on OS in all subgroups. CONCLUSIONS: A low pre-treatment LMR seems to represent an unfavorable and robust prognostic factor for clinical outcomes in patients with non-hematologic malignancies. FUNDING: None.


Assuntos
Linfócitos/citologia , Monócitos/citologia , Neoplasias/sangue , Progressão da Doença , Intervalo Livre de Doença , Humanos , Contagem de Linfócitos , Neoplasias/mortalidade , Prognóstico , Modelos de Riscos Proporcionais
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