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1.
J Chemother ; : 1-7, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38303601

RESUMO

Anti-PD-1/PD-L1 plus chemotherapy (CT) is considered the standard of care in first line treatment of metastatic NSCLC. However, the clinical benefit of this combination in older patients is controversial. We performed a meta-analysis of phase III randomized trials that compared PD-1/PD-L1 inhibitor plus CT with CT alone in first line of treatment for older patients with advanced NSCLC. Subgroups of patients over 65 and over 75 were analyzed. The outcomes included overall survival (OS) and progression-free survival (PFS). A fixedeffect model was used. We analyzed ten trials with an anti-PD-1 (camrelizumab, cemiplimab, nivolumab, pembrolizumab, tislelizumab or toripalimab) and six trials with an anti-PD-L1 (atezolizumab, durvalumab or sugemalimab), including 3666 patients over the age of 65 (41%) and 282 patients over the age of 75 (<10%). For patients over 65 years of age, anti-PD- 1/PD-L1 + CT was significantly associated (hazard ratio [95% confidence interval]) with prolonged OS (0.79 [0.72-0.86]; p < 0.00001) and P FS (0.63 [0.58-0.68]; p < 0.00001) compared to CT alone. Survival benefits occurred in both anti-PD-1 and anti-PD-L1 trials. For patients over 75 years of age, OS benefit was not statistically significant (0.88 [0.67-1.16]; p = 0.37). For patients over the age of 65 with untreated NSCLC, the anti-PD-1/PD-L1 combination with CT, compared with CT alone, is associated with significantly improved OS and PFS. Due to the low number of patients, it is difficult to conclude for those over 75.

2.
Nutrients ; 15(6)2023 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-36986238

RESUMO

Older cancer patients have an elevated risk of sarcopenia. The aim was to estimate the prevalence of four criteria for sarcopenia case finding, assessment, diagnosis, and severity determination: abnormal strength, assistance with walking, rising from a chair, climbing stairs, and falls (SARC-F), low hand-grip strength (HGS), low arm circumference (AC, a muscle mass proxy), and low physical performance (PP). Sarcopenia (low HGS and AC) and severe sarcopenia (low HGS, AC, and PP) and their predictive values for 6-month mortality were estimated in the whole population and by metastatic status. We analyzed data from the NutriAgeCancer French nationwide study of cancer patients aged ≥70 referred for geriatric assessment before anti-cancer treatment. We performed Cox proportional hazards analysis for each criterion separately and all criteria combined. Overall, 781 patients from 41 geriatric oncology clinics were included (mean age: 83.1; females: 53%; main cancer types: digestive (29%) and breast (17%); metastases: 42%). The prevalence of abnormal SARC-F, low HGS, a low AC, low PP, sarcopenia, and severe sarcopenia were, respectively, 35.5%, 44.6%, 44.7%, 35.2%, 24.5%, and 11.7%. An abnormal SARC-F and/or low HGS, sarcopenia, and severe sarcopenia were associated with 6-month mortality in patients with metastases (adjusted hazard ratios [95% confidence interval]: 2.72 [1.34-5.49], 3.16 [1.48-6.75] and 6.41 [2.5-16.5], respectively). Sarcopenia was strongly predictive of 6-month mortality in patients with metastatic cancer.


Assuntos
Neoplasias , Sarcopenia , Idoso , Feminino , Humanos , Idoso de 80 Anos ou mais , Sarcopenia/epidemiologia , Sarcopenia/diagnóstico , Estudos Prospectivos , Prevalência , Inquéritos e Questionários , Força da Mão/fisiologia , Avaliação Geriátrica , Neoplasias/complicações
3.
Cancer Immunol Immunother ; 71(3): 719-726, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34378081

RESUMO

PURPOSE: The most frequent mutation in advanced non-small-cell lung cancer (NSCLC), Kirsten rat-sarcoma viral oncogene (KRAS) is found in 20-25% of these patients' tumors. While phase III trials on therapies targeting KRAS, especially KRASG12C, are ongoing, the clinical efficacy of anti-programmed death protein-1 (PD-1) or its ligand (PD-L1) against KRAS-mutant NSCLCs remains a topic of debate. METHODS: This meta-analysis examined randomized-trial data comparing first- or second-line anti-PD-(L)1 with or without chemotherapy vs. chemotherapy alone for advanced KRAS-mutant NSCLCs. Outcome measures included overall survival (OS) and progression-free survival (PFS). Analyses were computed using the Cochrane method of collaboration for meta-analyses, with Review Manager software (RevMan version 5.3; Oxford, UK). RESULTS: We analyzed 3 first-line trials (IMpower-150, Keynote-189 and Keynote-042) and 3 second-line trials (Oak, Poplar and CheckMate-057) that included 1313 NSCLCs (386 KRAS-mutant and 927 KRAS wild-type tumors). For KRAS-mutant NSCLCs, anti-PD-(L)1 with or without chemotherapy was significantly associated (hazard ratio [95% confidence interval]) with prolonged OS (0.59 [0.49-0.72]; p < 0.00001) and PFS (0.58 [0.43-0.78]; p = 0.0003) compared to chemotherapy alone. OS benefited in both first- and second-line trials. OS for patients with KRAS-mutant NSCLCs was significantly longer than that for those with KRAS wild-type tumors (p = 0.001). CONCLUSIONS: Anti-PD-(L)1 with or without chemotherapy seemed to achieve longer OS and PFS than chemotherapy alone for patients with KRAS-mutant and wild-type KRAS advanced NSCLCs, with an even greater OS benefit for the former.


Assuntos
Antígeno B7-H1/antagonistas & inibidores , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Gerenciamento Clínico , Humanos , Inibidores de Checkpoint Imunológico/administração & dosagem , Inibidores de Checkpoint Imunológico/efeitos adversos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidade , Terapia de Alvo Molecular , Mutação , Modelos de Riscos Proporcionais , Ensaios Clínicos Controlados Aleatórios como Assunto , Retratamento , Resultado do Tratamento
4.
Cancers (Basel) ; 13(7)2021 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-33800614

RESUMO

Although organized, low-dose, computed-tomography (CT) scan lung-cancer screening has been shown to lower all-cause and lung-cancer-specific mortality, the primary cause of death for subjects eligible for such screening remains cardiovascular (CV) mortality. This meta-analysis study was undertaken to evaluate the impact of screening-scan-detected coronary artery calcifications (CACs) on CV and all-cause mortality. We conducted a systematic review and meta-analysis of studies reporting CV mortality according to the Agatson CAC score for participants in a lung-cancer screening program of randomized clinical or cohort studies. PubMed, Embase, and Cochrane databases were screened in June 2020. Two authors independently selected articles and extracted data. Six studies, including 20,175 subjects, were retained. CV and all-cause mortality rates were higher for subjects with CAC scores >0, with respective relative risks of 2.02 [95% CI 1.23-3.32] and 2.29 [95% CI 1.00-5.21]. Both mortality rates were even higher for those with high CAC scores (>400 or >1000). CACs are more common in men than in women, with an odds ratio of 1.49 [95% CI 1.40-1.59]. The presence of CAC is associated with CV mortality with an RR of 2.05 [95% CI 1.20-3.57] in men and 2.37 [CI 95% 1.29-5.09] in women, respectively. Analysis of lung-cancer-screening scans for CACs is a tool able to predict CV mortality. Prospective studies within those programs are needed to assess the benefit of primary CV prevention based on CAC detection.

5.
J Cancer Res Clin Oncol ; 146(2): 441-448, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31686247

RESUMO

AIMS: Single-agent anti-PD-1/PD-L1 clinical efficacy against < 1% PD-L1-expressing non-small-cell lung cancers (NSCLCs) is controversial. METHODS: This meta-analysis examined randomized-trial data comparing first-line PD-1/PD-L1-inhibitor + chemotherapy (CT) vs CT alone for advanced < 1% PD-L1 NSCLCs. Outcome measures included overall survival (OS), progression-free survival (PFS) and objective response rate (ORR). RESULTS: IMpower (atezolizumab + CT), Keynote (pembrolizumab + CT) and CheckMate (nivolumab + CT) trials included 2037 NSCLCs (1246 PD-L1-negative; 791 < 1% PD-L1 expression). Anti-PD-1/PD-L1 + CT was significantly associated (hazard ratio [95% confidence interval]) with prolonged OS (0.75 [0.63-0.89]; p = 0.0008) and PFS (0.72 [0.65-0.80]; p < 0.0001), and higher ORR (odds ratio 2.06 [1.50-2.83]; p < 0.0001). CONCLUSIONS: First-line anti-PD-1/PD-L1 + CT combination appears superior to CT alone for advanced, < 1% PD-L1-expressing NSCLCs for OS, PFS and ORR.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Humanos , Neoplasias Pulmonares/imunologia , Nivolumabe/administração & dosagem , Receptor de Morte Celular Programada 1/imunologia , Ensaios Clínicos Controlados Aleatórios como Assunto
6.
Clin Genitourin Cancer ; 17(4): e806-e813, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31227430

RESUMO

BACKGROUND: Results from large randomized controlled trials combining docetaxel, abiraterone, celecoxib, or bisphosphonates with androgen deprivation therapy (ADT) in hormone-sensitive prostate cancer have emerged. However, in our knowledge, few data are available in patients older than 70 years. Therefore, we undertook a meta-analysis of all published phase III studies. MATERIALS AND METHODS: We performed a PubMed search using the keywords: "hormone sensitive prostate cancer," "phase III studies," "docetaxel," "abiraterone," "celecoxib," and "bisphosphonates." We also screened American Society of Clinical Oncology and European Society for Medical Oncology proceedings. Combination therapies were compared with ADT alone. The efficacy outcomes were overall survival (OS) and progression-free survival (PFS). Hazard ratios (HRs) with their 95% confidence intervals (CIs) were collected from the studies and pooled. A hazard ratio of less than 1.00 favored the combination group. RESULTS: This meta-analysis included 8 studies: 3 assessed docetaxel (CHAARTED, STAMPEDE arm E and C), 2 others assessed abiraterone (LATITUDE and STAMPEDE arm G); 2 others assessed celecoxib (STAMPEDE arm D and F), and the last one assessed zoledronic acid alone (STAMPEDE arm B). Our meta-analysis included 2264 patients (86% with metastases). Concerning age, we chose a cutoff of 70 years, corresponding to the available data for each study. The performance index was 0 to 1 for about 90% of patients. Overall, in patients > 70 years old, the addition of docetaxel statistically improved PFS (HR, 0.51; 95% CI, 0.42-0.61) but not OS (HR, 0.86; 95% CI, 0.69-1.07). The addition of abiraterone to ADT also statistically improved PFS (HR, 0.49; 95% CI, 0.37-0.64) but not OS (HR, 0.85; 95% CI, 0.67-1.08), as well as the addition of celecoxib (HR, 0.67; 95% CI, 0.53-0.85 and HR, 0.95; 95% CI, 0.73-1.25, respectively). The addition of zoledronic acid did not improve PFS or OS (HR, 0.78; 95% CI, 0.61-1.00 and HR, 0.99; 95% CI, 0.71-1.38, respectively). CONCLUSIONS: The addition of docetaxel, abiraterone, or celecoxib to ADT significantly increased PFS in older men with hormone-sensitive advanced prostate cancer. However, the benefit in OS is not statistically significant. Further studies are needed to define the best first-line strategy in this subgroup.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Androstenos/uso terapêutico , Celecoxib/uso terapêutico , Ensaios Clínicos Fase III como Assunto , Intervalo Livre de Doença , Docetaxel/uso terapêutico , Humanos , Masculino , Análise de Sobrevida , Resultado do Tratamento , Ácido Zoledrônico/uso terapêutico
7.
Int J Colorectal Dis ; 33(8): 1125-1130, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29680896

RESUMO

INTRODUCTION: The clinical benefit of double-front-line therapy (including oxaliplatin or irinotecan or bevacizumab plus 5-fluorouracil (5FU) or capecitabine) compared to monotherapy (5FU or capecitabine) in elderly (> 70 years) patients with metastatic colorectal cancer (MCRC) is controversial. We performed a meta-analysis of published randomized studies. MATERIALS AND METHODS: The selection of the studies was carried out using PubMed with the following keywords: "metastatic colorectal cancer," "elderly," "oxaliplatin," "irinotecan," "bevacizumab," "survival." The efficacy endpoints were overall survival (OS) and progression-free survival (PFS). Hazard ratios (HRs) with their 95% confidence intervals (CIs) were collected from the studies and pooled. By convention, an HR < 1 was a result in favor of biotherapy. RESULTS: This meta-analysis (MA) included ten studies: three assessing irinotecan (FFCD 2001-02, CAIRO, and an already published MA by Folprecht), three assessing oxaliplatin (FOCUS2, FFCD 2000-05, and a published study by De Gramont), and four assessing bevacizumab (PRODIGE-20, AVEX, AGITG-MAX, and "AVF2192g" by Kabbinavar). Our MA included 1652 patients (62% of men). Concerning age, we chose a cut-off of 70 years or a cut-off of 75 years, corresponding to the available data for each study. The performance index (PS) was 0-1 for about 90% of patients, with the exception of FFCD 2001-02 and FOCUS2 which included 30% of patients with PS2. Overall, the addition of bevacizumab to fluoropyrimidin statistically improves both OS and PFS (HR = 0.78; CI 0.63-0.96 and HR = 0.55; CI 0.44-0.67, respectively). The addition of oxaliplatin did not statistically improve OS (= 0.99; CI 0.85-1.17) but improves PFS (HR = 0.81; CI 0.67-0.97) as well as the addition of irinotecan (HR = 1.01; CI 0.84-1.22 and HR = 0.82; CI 0.68-1.00, respectively). CONCLUSION: In previously untreated elderly patients with MCRC, the addition of bevacizumab to fluoropyrimidin appears more effective in terms of OS or PFS than the addition of oxaliplatin or irinotecan.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Idoso , Bevacizumab/administração & dosagem , Camptotecina/administração & dosagem , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Humanos , Irinotecano/administração & dosagem , Leucovorina , Masculino , Compostos Organoplatínicos , Oxaliplatina/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto
8.
Soins Gerontol ; 22(127): 30-33, 2017.
Artigo em Francês | MEDLINE | ID: mdl-28917334

RESUMO

The arrival of new immunotherapies, called checkpoint inhibitors, is radically changing the world of oncology. Currently, there are some twenty different cancers which may respond to this type of therapy. It is therefore important that professionals involved in the care of elderly people with cancer are already made aware of these new treatments. This article explains how these checkpoint inhibitors work and describes their efficacy and their toxicity for elderly patients.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/efeitos adversos , França , Humanos , Tolerância Imunológica/efeitos dos fármacos , Neoplasias/enfermagem , Resultado do Tratamento
9.
Int J Colorectal Dis ; 30(10): 1305-10, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26099322

RESUMO

BACKGROUND: The clinical benefit of first-line doublet chemotherapy (including oxaliplatin or irinotecan) compared to single-drug therapy (5FU) in elderly patients (>70 or >75 years old) with metastatic colorectal cancer (MCRC) is controversial. Therefore, we undertook a meta-analysis of all published phase III studies. MATERIAL AND METHODS: We performed a PubMed search using keywords metastatic colorectal cancer, phase III studies, oxaliplatin, irinotecan, survival. We also screened Society of Clinical Oncology (ASCO) and European Society of Medical Oncology (ESMO) proceedings. Few studies have been published corresponding to our inclusion criteria. The efficacy outcomes were overall survival (OS) and progression-free survival (PFS). Toxicity was also examined when available. Hazard ratios (HRs) with their 95 % confidence intervals (CI) were collected from the studies and pooled. By convention, HRs <1 corresponded to a better outcome for doublets. p values <0.05 were considered statistically significant. A fixed-effect model was used. We used Comprehensive Meta-Analysis Software (Biostat, Englewood, NJ, USA). RESULTS: This meta-analysis (MA) included five original studies (Mitry and Venderbosch for CAIRO both assessing irinotecan, De Gramont and Seymour for FOCUS2 and Ducreux assessing oxaliplatin) and an already published MA (Folprecht) of four trials comparing FOLFIRI with 5FU (Saltz, Douillard, Köhne and Seymour). Our MA included 1225 patients (70 % men). For age, we chose a cut-off of 70 years for oxaliplatin and a cut-off of 75 years for irinotecan. The performance status (PS) score was 0-1 in about 90 % of patients except for the studies by Mitry and Seymour FOCUS2 which both included 30 % of PS2 patients. Overall, doublet chemotherapy, compared to 5FU alone, did not improve OS (HR = 1.00; CI: 0.89-1.13) but significantly improved PFS (HR = 0.82; CI: 0.72-0.93). When assessed separately, FOLFIRI and FOLFOX both significantly improved PFS (HR = 0.83; 0.68-1.00 and HR = 0.81; 0.68-0.97, respectively). The main grade 3-4 toxicities for FOLFIRI were diarrhoea, nausea, vomiting and neutropenia, which occurred significantly more often than with 5FU alone. CONCLUSION: Addition of oxaliplatin or irinotecan to 5FU in metastatic CRC significantly improved PFS in elderly patients more than 70 years old but was associated with an increased risk of toxicity as shown for irinotecan.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Fluoruracila/uso terapêutico , Idoso , Antineoplásicos Fitogênicos/efeitos adversos , Antineoplásicos Fitogênicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/efeitos adversos , Camptotecina/análogos & derivados , Camptotecina/uso terapêutico , Ensaios Clínicos Fase III como Assunto , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/secundário , Progressão da Doença , Humanos , Irinotecano , Compostos Organoplatínicos/efeitos adversos , Compostos Organoplatínicos/uso terapêutico , Oxaliplatina
10.
Soins Gerontol ; (99): 35-9, 2013.
Artigo em Francês | MEDLINE | ID: mdl-23409678

RESUMO

In France, the incidence and rate of mortality of cancer increase with age. For elderly patients suffering from cancer, the standard geriatric assessment, together with an oncological assessment aims to optimise the treatment. This geriatric oncology assessment enables the priorities to be identified and the cancer treatment to be adapted by anticipating the risks and organising the support care.


Assuntos
Avaliação Geriátrica , Neoplasias/terapia , Avaliação em Enfermagem , Gestão de Riscos , Idoso , Idoso de 80 Anos ou mais , Humanos
11.
Eur J Intern Med ; 14(7): 419-425, 2003 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-14614974

RESUMO

BACKGROUND: In recent years, cases of scurvy have mainly been described in populations at risk. The prevalence and risk factors for hypovitaminosis C among hospitalized patients in a department of internal medicine are largely unknown. METHODS: We determined serum ascorbic acid level (SAAL) and searched for clinical and biological signs of scurvy in 184 patients hospitalized during a 2-month period. RESULTS: The prevalence of hypovitaminosis C (depletion: SAAL<5 mg/l or deficiency: SAAL<2 mg/l ) was 47.3%. Some 16.9% of the patients had vitamin C deficiency. There was a strong association between hypovitaminosis C and the presence of an acute phase response (p=0.002). Other univariate risk factors for vitamin C depletion were male sex (p=0.02), being retired (p=0.037), and infectious diseases (p=0.002). For vitamin C deficiency, the significant univariate risk factors included the same ones found for vitamin C depletion, plus being unemployed (p=0.003) and concomitant excessive alcohol and tobacco consumption (p<0.0001). Logistic regression showed that being retired (p=0.015) and concomitant excessive alcohol and tobacco consumption (p=0.0003) were significant independent risk factors. Hemorrhagic syndrome and edema were described more often in patients with vitamin C deficiency than in those with vitamin C depletion or without hypovitaminosis. Clinical signs were more frequent for an ascorbic acid level below 2.5 mg/l. CONCLUSION: Hypovitaminosis C is frequent in hospitalized patients but should be interpreted according to the presence or absence of an acute phase response. The main risk factors are living conditions and excessive alcohol and tobacco consumption.

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