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1.
Anticancer Drugs ; 33(2): 220-224, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34845161

RESUMO

The authors present the case of a 94-year-old woman suffering from a right arm angiosarcoma developed after primary breast cancer and treated with success by oral metronomic chemotherapy based on daily low doses of cyclophosphamide and prednisone. The case description is followed by a short review of actual knowledge on the subject.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Braço/patologia , Hemangiossarcoma/tratamento farmacológico , Linfangiossarcoma/tratamento farmacológico , Administração Metronômica , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/complicações , Feminino , Hemangiossarcoma/etiologia , Humanos , Linfangiossarcoma/etiologia
2.
J Geriatr Oncol ; 12(3): 368-374, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33223483

RESUMO

BACKGROUND: This study aims to investigate the occurrence of unplanned hospitalizations in older patients with cancer and to determine predictive factors. METHODS: A prospective Belgian multicentre (n = 22), observational cohort study was performed. Patients ≥70 years with a malignant tumor were included. Patients underwent G8 screening followed by geriatric assessment (GA) if abnormal at baseline and were followed for unplanned hospitalizations at approximately three months. Uni- and multivariable regression models were performed to determine predictive factors associated with unplanned hospitalizations in older patients with an abnormal G8. RESULTS: In total, 7763 patients were included in the current analysis of which 2409 (31%) patients with a normal G8 score and 5354 (69%) with an abnormal G8 score. Patients with an abnormal G8 were hospitalized more frequently than patients with a normal G8 (22.9% versus 12.4%; p < 0.0001). Reasons for unplanned hospitalizations were most frequently cancer related (25.7%) or cancer therapy related (28%). In multivariable analysis, predictive factors for unplanned hospitalizations in older patients with cancer and an abnormal G8 were female gender, absence of surgery, chemotherapy, ADL dependency, malnutrition and presence of comorbidities. CONCLUSION: Older patients with cancer and an abnormal G8 screening present a higher risk (23%) for unplanned hospitalizations. Predictive factors for these patients were identified and include not only patient and treatment related factors but also GA related factors.


Assuntos
Avaliação Geriátrica , Neoplasias , Idoso , Bélgica/epidemiologia , Feminino , Hospitalização , Humanos , Neoplasias/epidemiologia , Neoplasias/terapia , Estudos Prospectivos
3.
Int J Cancer ; 2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33270911

RESUMO

The triplet combination of irinotecan, oxaliplatin and fluorouracil is an active frontline regimen in metastatic colorectal cancer, but scarce data exist on its use as salvage treatment. We aimed at assessing its safety and efficacy profiles with its circadian-based administration (chronoIFLO5) as either first- or second-line treatment, within the time-finding EORTC 05011 trial. Five-day chronoIFLO5 was administered every 3 weeks in patients with PS 0, 1 or 2. It consisted of chronomodulated irinotecan (180 mg/sqm), oxaliplatin (80 mg/sqm) and fluorouracil-leucovorin (2800 and 1200 mg/sqm, respectively). For our study, toxicity and antitumour activity were evaluated separately in first- and second-line settings. Primary endpoints included Grade 3-4 toxicity rates, best objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). One-hundred forty-nine and 44 patients were treated in first-line and second-line settings, respectively, with a total of 1138 cycles with median relative dose intensities of about 90%. Demographics were comparable in the two groups. Thirty-six (24.7%) and 10 (22.2%) patients experienced at least one episode of severe toxicity in first line and second line, respectively. Frontline chronoIFLO5 yielded an ORR of 62.3% [95% CI: 54.2-70.4] and resulted in median PFS and OS of 8.7 months [7.5-9.9] and 19.9 months [15.4-24.5]. Corresponding figures in second line were 37.5% [22.5-52.5], 6.7 months [4.8-8.9] and 16.3 months [11.8-20.8]. International and prospective evaluation revealed the favourable safety and efficacy profiles of chronoIFLO5, both as frontline and as salvage treatment against metastatic colorectal cancer. In particular, encouraging activity in second line was observed, with limited haematological toxicity.

4.
Anticancer Res ; 40(8): 4253-4261, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32727752

RESUMO

BACKGROUND/AIM: A prospective non-randomized study was performed on 68 women who had recently undergone curative treatment (surgery +/- adjuvant radio/chemotherapy) for breast cancer. PATIENTS AND METHODS: Patients were distributed into 2 subgroups, control (C) group (n=21) and experimental (E) group (n=47). The last group participated in a 12-week rehabilitation program associating physical activity and psychoeducational workshops, including management of stress, diet, and sleep disorders. RESULTS: Despite the initial imbalance between the groups (patients from C group were older and had received less chemotherapy than those from the E group), at the end of the rehabilitation program, we observed a significant improvement in global health feeling and in objective physical tests (distance covered in 6 min and objective measures of ergospirometry), and a decrease in pathological fatigue, while these different items remained quite stable over time in the control group. CONCLUSION: It is suggested to recommend structured rehabilitation to any patient who does not have a contraindication to it. In addition, the scientific literature encourages us to extend the spectrum of oncological rehabilitation to pathologies other than breast cancer.


Assuntos
Neoplasias da Mama/reabilitação , Exercício Físico , Estilo de Vida , Adulto , Idoso , Bélgica , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/psicologia , Neoplasias da Mama/terapia , Estudos de Casos e Controles , Detecção Precoce de Câncer , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos
5.
J Geriatr Oncol ; 11(6): 926-936, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32305251

RESUMO

OBJECTIVES: We aimed to determine the prognostic value of baseline Health-Related Quality Of Life (HRQOL) and geriatric assessment (GA) to predict three-month mortality in older patients with cancer undergoing treatment. METHODS: Logistic regressions analysed HRQOL, as measured with the EORTC Global Health Status (GHS) scale, and geriatric information prognostic for early mortality controlling for oncology variables. The assessment was established with the odds ratio (OR), 95% confidence interval (CI) and level of significance set at p < 0.05. Discriminative power was evaluated with area under the curve (AUC). RESULTS: In total, 6769 patients were included in the study, of whom 1259 (18.60%) died at three months. Our model showed higher odds of early death for patients with lower HRQOL (GHS, OR 0.98, 95% CI 0.98-0.99; p < 0.001), a geriatric risk profile (G8 Screening Tool, 1.94, 1.14-3.29; p = 0.014), cognitive decline (Mini Mental State Examination, 1.41, 1.15-1.72; p = 0.001), being at risk for malnutrition (Mini Nutritional Assessment-Short Form, 1.54, 1.21-1.98; p = 0.001), fatigue (Visual Analogue Scale for Fatigue, 1.45, 1.16-1.82; p = 0.012) and comorbidities (Charlson Comorbidity index, 1.23, 1.02-1.49; p = 0.033). Additionally, older age, poor ECOG PS and being male increased the odds of early death, although the magnitude differed depending on tumor site and stage, and treatment (all p < 0.05). Predictive accuracy increased with 3.7% when including HRQOL and GA in the model. CONCLUSION: The results suggest that, in addition to traditional clinical measures, HRQOL and GA provide additional prognostic information for early death, but the odds differ by patient and tumor characteristics.


Assuntos
Avaliação Geriátrica , Neoplasias , Medidas de Resultados Relatados pelo Paciente , Idoso , Feminino , Humanos , Masculino , Neoplasias/terapia , Prognóstico , Qualidade de Vida
6.
Cancer Med ; 9(12): 4148-4159, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32319740

RESUMO

The least toxic time (LTT) of irinotecan varied by up to 8 hours according to sex and genetic background in mice. The translational relevance was investigated within a randomized trial dataset, where no LTT stood out significantly in the whole population. 130 male and 63 female eligible patients with metastatic colorectal cancer were randomized to receive chronomodulated Irinotecan with peak delivery rate at 1 of 6 clock hours staggered by 4 hours on day 1, then fixed-time chronomodulated Fluorouracil-Leucovorin-Oxaliplatin for 4 days, q3 weeks. The sex-specific circadian characteristics of grade (G) 3-4 toxicities were mapped with cosinor and time*sex interactions confirmed with Fisher's exact test. Baseline characteristics of male or female patients were similar in the six treatment groups. Main grade 3-4 toxicities over six courses were diarrhea (males vs females, 39.2%; vs 46.0%), neutropenia (15.6% vs 15.0%), fatigue (11.5% vs 15.9%), and anorexia (10.0% vs 7.8%). They were reduced following irinotecan peak delivery in the morning for males, but in the afternoon for females, with statistically significant rhythms (P < .05 from cosinor) and sex*timing interactions (Fisher's exact test, diarrhea, P = .023; neutropenia, P = .015; fatigue, P = .062; anorexia, P = .032). Irinotecan timing was most critical for females, with grades 3-4 ranging from 55.2% of the patients (morning) to 29.4% (afternoon) for diarrhea, and from 25.9% (morning) to 0% (afternoon) for neutropenia. The study results support irinotecan administration in the morning for males and in the afternoon for females, in order to minimize adverse events without impairing efficacy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Colorretais/patologia , Relação Dose-Resposta a Droga , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Europa (Continente)/epidemiologia , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Irinotecano/administração & dosagem , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Oxaliplatina/administração & dosagem , Prognóstico , Caracteres Sexuais , Taxa de Sobrevida
7.
J Geriatr Oncol ; 10(6): 895-903, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31005649

RESUMO

OBJECTIVES: This study aims to investigate health-related quality of life (HRQOL) at baseline and at follow-up in older patients with cancer and to determine prognostic factors for HRQOL decline. METHODS: A prospective Belgian multicentre (n = 22) study was performed. Patients ≥70 years with a malignant tumor and abnormal G8 (≤14/17) screening tool were included. Patients underwent geriatric assessment (GA) and HRQOL evaluation with follow up at three months. Uni- and multivariate regression models were performed to determine factors associated (p < .05) with baseline HRQOL and HRQOL decline at follow-up. RESULTS: Results reflect data collected from 3673 patients. A multivariate analysis showed that younger patients, and those with poor Eastern Cooperative Oncology Group - Performance Status (ECOG-PS), specific tumor types (gastrointestinal, gynaecological and thorax) and higher stage had lower baseline HRQOL. In addition worse functional status and presence of pain, fatigue, depression and malnutrition were associated with lower baseline HRQOL. During treatment (n = 2972), improvement in HRQOL was observed in 1037 patients (35%) and a decline in 838 patients (28.2%). In multivariate analysis, stage and presence of baseline comorbidities, pain, fatigue or malnutrition were associated with HRQOL evolution. CONCLUSION: Baseline HRQOL in older patients with cancer and an abnormal G8 depends on tumor and age related parameters. During follow-up, HRQOL improved in one third of patients, indicating that they may benefit from cancer treatment while one quarter demonstrated a HRQOL decline for which prognostic factors were identified.


Assuntos
Atividades Cotidianas , Avaliação Geriátrica/métodos , Neoplasias/psicologia , Qualidade de Vida , Idoso , Idoso de 80 Anos ou mais , Dor do Câncer/epidemiologia , Comorbidade , Fadiga/epidemiologia , Feminino , Humanos , Masculino , Neoplasias/epidemiologia , Neoplasias/terapia , Estudos Prospectivos
8.
Eur J Cancer ; 87: 10-20, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29096156

RESUMO

BACKGROUND: In cancer follow-up, in addition to the evaluation of survival probabilities, there is a fundamental need of assessing recurrence dynamics for optimal disease management. Although the time-dependent effect of the oestrogen receptor (ER) status of the tumour has already been described, so far no factor has proven to disentangle the multi-peak behaviour observed for breast cancer recurrences. Here, we aimed at investigating whether adiposity at diagnosis, reflected by increased patient's body mass index (BMI), could be associated with breast cancer recurrence patterns over time after primary cancer therapy. METHODS: We retrieved BMI from 734 of 777 patients with node-positive breast cancer from a phase III randomised clinical trial, which compared different chemotherapy regimens and had a median follow-up of 15.4 years. Cumulative incidence estimation as well as piecewise exponential models were carried out to estimate the distant recurrence dynamics, in all patients, as well as in subgroups based on the ER status, with the ER-positive group being further split according to the menopausal status. RESULTS: In patients with ER-negative breast cancer, time-dependent analyses revealed that the hazard of late relapses could mainly be attributed to the overweight and obese patients. Within the subgroup of premenopausal patients with ER-positive tumours, obesity was associated with an early high narrow peak of distant recurrences followed by another main peak after 5 years of follow-up. The risk for overweight patients was intermediate between obese and normal-weight patients. In the postmenopausal subgroup of patients with ER-positive tumours, the distant recurrence rate was significantly more elevated in the overweight patients compared to the other BMI categories, and a second late peak of recurrences was also observed for the obese patients. CONCLUSION: These results demonstrate that the patient's BMI at diagnosis is associated with cancer recurrence dynamics. Patient adiposity should therefore be central to the exploration of late adjuvant treatment modalities.


Assuntos
Adiposidade , Índice de Massa Corporal , Neoplasias da Mama/terapia , Recidiva Local de Neoplasia , Obesidade/epidemiologia , Biomarcadores Tumorais/análise , Neoplasias da Mama/química , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Feminino , Humanos , Incidência , Estimativa de Kaplan-Meier , Metástase Linfática , Pessoa de Meia-Idade , Análise Multivariada , Obesidade/diagnóstico , Obesidade/fisiopatologia , Modelos de Riscos Proporcionais , Receptores de Estrogênio/análise , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
9.
Br J Cancer ; 117(7): 965-973, 2017 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-28817838

RESUMO

BACKGROUND: The hepatic artery infusion (HAI) of irinotecan, oxaliplatin and 5-fluorouracil with intravenous cetuximab achieved outstanding efficacy in previously treated patients with initially unresectable liver metastases from colorectal cancer. This planned study aimed at the identification of pharmacogenetic predictors of outcomes. METHODS: Circulating mononuclear cells were analysed for 207 single-nucleotide polymorphisms (SNPs) from 34 pharmacology genes. Single-nucleotide polymorphisms passing stringent Hardy-Weinberg equilibrium test were tested for their association with outcomes in 52 patients (male/female, 36/16; WHO PS, 0-1). RESULTS: VKORC1 SNPs (rs9923231 and rs9934438) were associated with early and objective responses, and survival. For rs9923231, T/T achieved more early responses than C/T (50% vs 5%, P=0.029) and greatest 4-year survival (46% vs 0%, P=0.006). N-acetyltransferase-2 (rs1041983 and rs1801280) were associated with up to seven-fold more macroscopically complete hepatectomies. Progression-free survival was largest in ABCB1 rs1045642 T/T (P=0.026) and rs2032582 T/T (P=0.035). Associations were found between toxicities and gene variants (P<0.05), including neutropenia with ABCB1 (rs1045642) and SLC0B3 (rs4149117 and rs7311358); and diarrhoea with CYP2C9 (rs1057910), CYP2C19 (rs3758581), UGT1A6 (rs4124874) and SLC22A1 (rs72552763). CONCLUSION: VKORC1, NAT2 and ABCB1 variants predicted for HAI efficacy. Pharmacogenetics could guide the personalisation of liver-targeted medico-surgical therapies.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Arilamina N-Acetiltransferase/genética , Neoplasias Colorretais/genética , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Vitamina K Epóxido Redutases/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Administração Intravenosa , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Proteínas da Membrana Plasmática de Transporte de Catecolaminas/genética , Cetuximab/administração & dosagem , Neoplasias Colorretais/patologia , Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP2C9/genética , Diarreia/induzido quimicamente , Diarreia/genética , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Glucuronosiltransferase/genética , Hepatectomia , Artéria Hepática , Humanos , Infusões Intra-Arteriais , Irinotecano , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Neutropenia/genética , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Farmacogenética , Polimorfismo de Nucleotídeo Único , Taxa de Sobrevida , Resultado do Tratamento
10.
Clin Pharmacokinet ; 56(2): 165-177, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27393140

RESUMO

The combination of hepatic artery infusion (HAI) of irinotecan, 5-fluorouracil and oxaliplatin with intravenous cetuximab has safely achieved prolonged survival in colorectal cancer patients with extensive liver metastases and prior treatment. Systemic exposure to the drugs or their main metabolites was determined during the first course of chronomodulated triplet HAI in 11 patients and related to toxicities after one or three courses. Consistent trends were found between the area under the plasma concentration-time curve (AUC) values of irinotecan, 7-ethyl-10-hydroxycamptothecin (SN38; a bioactive metabolite), total oxaliplatin and platinum ultrafiltrate (P-UF), on the one hand, and subsequent leukopenia severity, on the other hand. Moreover, the maximum plasma concentration (C max) and the AUC of P-UF significantly predicted grades of diarrhoea (p = 0.004 and 0.017, respectively) and anaemia (p = 0.001 and 0.008, respectively) after the first course. Systemic drug exposure helps explain both the adverse events and the low rate of extrahepatic progression-a usual drawback of HAI chemotherapy-thus supporting upfront testing of the regimen. Systems optimization of chronomodulated HAI delivery could further reduce adverse events.


Assuntos
Camptotecina/análogos & derivados , Cronoterapia Farmacológica , Fluoruracila/farmacocinética , Artéria Hepática/metabolismo , Neoplasias Hepáticas/sangue , Compostos Organoplatínicos/farmacocinética , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Camptotecina/administração & dosagem , Camptotecina/farmacocinética , Neoplasias Colorretais/sangue , Neoplasias Colorretais/tratamento farmacológico , Europa (Continente)/epidemiologia , Feminino , Fluoruracila/administração & dosagem , Artéria Hepática/efeitos dos fármacos , Humanos , Infusões Intra-Arteriais/métodos , Irinotecano , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina
11.
Eur J Cancer ; 68: 163-172, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27768923

RESUMO

BACKGROUND: Early tumour shrinkage has been associated with improved survival in patients receiving cetuximab-based systemic chemotherapy for liver metastases from colorectal cancer (LM-CRC). We tested this hypothesis for previously treated LM-CRC patients receiving cetuximab (500 mg/m2) and triplet hepatic artery infusion (HAI) within European trial OPTILIV. METHODS: Irinotecan (180 mg/m2), 5-fluorouracil (2800 mg/m2) and oxaliplatin (85 mg/m2) were given as chronomodulated or conventional delivery. Patients were retrospectively categorised as early responders (complete or partial RECIST response after three courses) or non-early responders (late or no response). Prognostic factors were determined using multivariate logistic or Cox regression models. RESULTS: Response was assessed in 57 of 64 registered patients (89%), who had previously received one to three prior systemic chemotherapy protocols. An early response occurred at 6 weeks in 16 patients (28%; 9 men, 7 women), aged 33-76 years, with a median of 12 liver metastases (LMs) (2-50), involving five segments (1-8). Ten patients had a late response, and 31 patients had no response. Grade 3-4 fatigue selectively occurred in the non-early responders (0% versus 26%; p = 0.024). Early tumour response was jointly predicted by chronomodulation-odds ratio (OR): 6.0 (1.2-29.8; p = 0.029)-and LM diameter ≤57 mm-OR: 5.3 (1.1-25.0; p = 0.033). Early tumour response predicted for both R0-R1 liver resection-OR: 11.8 (1.4-100.2; p = 0.024) and overall survival-hazard ratio: 0.39 (0.17-0.88; p = 0.023) in multivariate analyses. CONCLUSIONS: Early tumour response on triplet HAI and systemic cetuximab predicted for complete macroscopic liver resection and prolonged survival for LM-CRC patients within a multicenter conversion-to-resection medicosurgical strategy. Confirmation is warranted for early response on HAI to guide decision making. Protocol numbers: EUDRACT 2007-004632-24 NCT00852228.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Adenocarcinoma/secundário , Adulto , Idoso , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Cetuximab/administração & dosagem , Neoplasias Colorretais/patologia , Fadiga/induzido quimicamente , Feminino , Fluoruracila/administração & dosagem , Artéria Hepática , Humanos , Infusões Intra-Arteriais , Infusões Intravenosas , Irinotecano , Neoplasias Hepáticas/secundário , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento
12.
PLoS One ; 11(3): e0147599, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27032107

RESUMO

INTRODUCTION: Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibition is the preferred first-line treatment of advanced adenocarcinoma of the lung that harbors EGFR activating tyrosine kinase domain mutations. Most data available pertain to Asian populations in which such mutations are more prevalent. We report on the long-term results of first-line treatment with erlotinib in Caucasian patients with advanced adenocarcinoma of the lung that have a somatic EGFR mutation in their tumor. METHODS: Multicenter academic prospective phase II study with erlotinib in patients with an activating EGFR tyrosine kinase (TK) domain somatic mutation (any exon encoding the kinase domain) in the tumor and no prior treatment for their advanced disease. RESULTS: Phenotypic preselecting of 229 patients led to a high EGFR mutation detection rate of 24% of which 46 patients were included in the phase II study. With a progression free survival (PFS) of 81% at three months the study met its primary endpoint for presumed superiority over chemotherapy. With an overall median PFS of 11 months and a median overall survival (OS) of 23 months, the results compare favorably with results obtained in randomized studies using TKI in first line in EGFR mutation positive adenocarcinoma of the lung. CONCLUSION: The present study reinforces the use of EGFR tyrosine kinase inhibition (TKI) as a first line treatment of choice for advanced adenocarcinoma of the lung carrying an activating EGFR mutation. The mutation rate in preselected Caucasian patients is higher than previously reported. Issues relevant for clinical practice are discussed. TRIAL REGISTRATION: ClinicalTrials.gov NCT00339586.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Cloridrato de Erlotinib/uso terapêutico , Mutação/genética , /genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise Mutacional de DNA , Cloridrato de Erlotinib/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Análise de Sobrevida , Resultado do Tratamento
13.
Anticancer Res ; 35(11): 6311-5, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26504068

RESUMO

AIM: To determine if actively-treated cancer patients developing cachexia could benefit from participation to mindfulness workshops. PATIENTS AND METHODS: Subjects developing cachexia signs while treated for cancer were randomized in a trial aiming to compare an experimental group that would participate to specific workshops based on mindfulness alternating dietetic and psychological approaches, and a control group managed in accordance to usual practice. RESULTS: The recruitment was difficult (12% of the approached population). Finally 53 patients accepted to participate. Despite an unpredictable compliance of workshop participants, the final satisfaction score attained 75%. In comparison with the control group, patients randomized to the experimental group showed a significant benefit with an increase of their body weight and an improvement of their WHO status score. They also experienced an improvement of emotional function and observation faculty as well as a relief of fatigue and some digestive disorders. CONCLUSION: Selected cachectic cancer patients may benefit from this experimental approach. This approach may, however, be difficult to implement on a large scale.


Assuntos
Adaptação Psicológica , Caquexia/prevenção & controle , Caquexia/psicologia , Dietética , Atenção Plena , Neoplasias/complicações , Qualidade de Vida , Adulto , Idoso , Caquexia/etiologia , Estudos de Casos e Controles , Gerenciamento Clínico , Emoções , Fadiga/etiologia , Fadiga/prevenção & controle , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias/patologia , Prognóstico , Estresse Psicológico/prevenção & controle , Inquéritos e Questionários
14.
Eur J Cancer ; 51(17): 2517-24, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26321502

RESUMO

BACKGROUND: Epirubicin-based chemotherapy improves the outcome of early breast cancer (BC) patients. However, cardiotoxicity remains an important side effect. METHODS: We re-consented node-positive BC patients enrolled in a phase III trial between 1988 and 1996 which compared six cycles of oral cyclophosphamide, methotrexate, fluorouracil (CMF) versus two epirubicin-cyclophosphamide regimens differing by the anthracycline cumulative dose [standard-dose epirubicin and cyclophosphamide (SDE) (8 × 60 mg/m(2)) and higher-dose epirubicin and cyclophosphamide (HDE) (8 × 100 mg/m(2))]. Eligible patients were those who were alive and free of disease and had no contra-indications to the proposed tests (cardiac evaluation). Cardiotoxicity was defined as asymptomatic systolic dysfunction (left ventricular ejection fraction (LVEF)< 50%, New York Heart Association (NYHA) Class I) or symptomatic heart failure (NYHA Class II-IV). Differences in cardiotoxicity between CMF and SDE/HDE were assessed using chi-square and Fisher Exact tests for binary variables and t-test and Wilcoxon test for continuous variables. RESULTS: Among the 777 patients, 20 cases of CHF were reported (CMF = 1, SDE = 5, HDE = 14; p < 0.001). Between September 2010 and June 2013, 82 patients (30%) out of 269 eligible patients accepted to participate in this substudy. Median follow-up was 18 years (range 15-24). Epirubicin-treated patients had significantly higher heart rate, more abnormal echocardiograms and LVEF by magnetic resonance imaging (MRI) compared to CMF-treated ones. A trend towards higher BNP was also observed in the SDE/HDE group (P = 0.08). No differences were observed in LVEF assessed by echocardiogram or troponin T levels. CONCLUSIONS: Participation rate in this substudy was lower than expected highlighting the complexity of re-calling patients several years after the initial BC diagnosis. After 18 years, epirubicin-treated patients had a lower LVEF by MRI, more abnormal echocardiograms, higher heart rates compared to patients treated with CMF. However, no major delayed cardiotoxicity was observed.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/mortalidade , Quimioterapia Adjuvante/métodos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Ecocardiografia , Epirubicina/administração & dosagem , Epirubicina/efeitos adversos , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Seguimentos , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/fisiopatologia , Humanos , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Prognóstico , Modelos de Riscos Proporcionais , Taxa de Sobrevida , Disfunção Ventricular Esquerda/induzido quimicamente , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/fisiopatologia
15.
Chronobiol Int ; 31(8): 891-900, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24927369

RESUMO

The disruption of the circadian timing system (CTS), which rhythmically controls cellular metabolism and proliferation, accelerated experimental cancer progression. A measure of CTS function in cancer patients could thus provide novel prediction information for outcomes, and help to identify novel specific therapies. The rest-activity circadian rhythm is a reliable and non-invasive CTS biomarker, which was monitored using a wrist watch accelerometer for 2 days in 436 patients with metastatic colorectal cancer. The relative percentage of activity in-bed versus out-of-bed (I < O) constituted the tested CTS measure, whose prognostic value for overall survival (OS) and progression-free survival (PFS) was determined in a pooled analysis of three patient cohorts with different treatment exposures. Median OS was 21.6 months [17.8-25.5] for patients with I < O above the median value of 97.5% as compared to 11.9 months [10.4-13.3] for those with a lower I < O (Log-rank p < 0.001). Multivariate analyses retained continuous I < O as a joint predictor of both OS and PFS, with respective hazard ratios (HR) of 0.954 (p < 0.001) and 0.970 (p < 0.001) for each 1% increase in I < O. HRs had similar values in all the patient subgroups tested. The circadian physiology biomarker I < O constitutes a robust and independent quantitative predictor of cancer patient outcomes, that can be easily and cost-effectively measured during daily living. Interventional studies involving 24-h schedules of clock-targeted drugs, light intensity, exercise and/or meals are needed for testing the relevance of circadian synchronization for the survival of patients with disrupted rhythms.


Assuntos
Actigrafia/métodos , Ritmo Circadiano , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/mortalidade , Monitorização Ambulatorial/métodos , Punho/fisiopatologia , Aceleração , Adulto , Idoso , Antineoplásicos/uso terapêutico , Biomarcadores/metabolismo , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Metástase Neoplásica , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
16.
Cancer ; 119(14): 2564-73, 2013 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-23633399

RESUMO

BACKGROUND: Chemotherapy-induced neutropenia has been associated with prolonged survival selectively in patients on a conventional schedule (combined 5-fluorouracil, leucovorin, and oxaliplatin [FOLFOX2]) but not on a chronomodulated schedule of the same drugs administered at specific circadian times (chronoFLO4). The authors hypothesized that the early occurrence of chemotherapy-induced symptoms correlated with circadian disruption would selectively hinder the efficacy of chronotherapy. METHODS: Fatigue and weight loss (FWL) were considered to be associated with circadian disruption based on previous data. Patients with metastatic colorectal cancer (n = 543) from an international phase 3 trial comparing FOLFOX2 with chronoFLO4 were categorized into 4 subgroups according to the occurrence of FWL or other clinically relevant toxicities during the initial 2 courses of chemotherapy. Multivariate Cox models were used to assess the role of toxicity on the time to progression (TTP) and overall survival (OS). RESULTS: The proportions of patients in the 4 subgroups were comparable in both treatment arms (P = .77). No toxicity was associated with TTP or OS on FOLFOX2. The median OS on FOLFOX2 ranged from 16.4 (95% confidence limits [CL], 7.2-25.6 months) to 19.8 months (95% CL, 17.7-22.0 months) according to toxicity subgroup (P = .45). Conversely, FWL, but no other toxicity, independently predicted for significantly shorter TTP (P < .0001) and OS (P = .001) on chronoFLO4. The median OS on chronoFLO4 was 13.8 months (95% CL, 10.4-17.2 months) or 21.1 months (95% CL, 19.0-23.1 months) according to presence or absence of chemotherapy-induced FWL, respectively. CONCLUSIONS: Early onset chemotherapy-induced FWL was an independent predictor of poor TTP and OS only on chronotherapy. Dynamic monitoring to detect early chemotherapy-induced circadian disruption could allow the optimization of rapid chronotherapy and concomitant improvements in safety and efficacy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/mortalidade , Cronoterapia Farmacológica , Fadiga , Redução de Peso , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Colorretais/patologia , Progressão da Doença , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Humanos , Estimativa de Kaplan-Meier , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Compostos Organoplatínicos/administração & dosagem , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Resultado do Tratamento
18.
Chronobiol Int ; 28(7): 586-600, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21859417

RESUMO

Circadian clocks control cellular proliferation and drug metabolism over the 24 h. However, circadian chronomodulated chemotherapy with 5-fluorouracil, leucovorin, and oxaliplatin (chronoFLO4) offered no survival benefit as compared with the non-time-stipulated FOLFOX2, in an international randomized trial involving patients with previously untreated metastatic colorectal cancer (EORTC 05963). The authors hypothesized that treatment near maximum tolerated dose could disrupt circadian clocks thus impairing the efficacy of chronoFLO4 but not of FOLFOX2. Patients with available data (N = 556) were categorized into three subgroups according to the worst grade (G) of neutropenia experienced during treatment. Distinct multivariate models with time-dependent covariates were constructed for each treatment schedule. Neutropenia incidence (all grades) was 33% on chronoFLO4 and 61% on FOLFOX2 (p < .0001), and G3-4 were 7% and 25%, respectively (p < .0001). Neutropenia was significantly more frequent in women than men on either schedule (FOLFOX2, p = .003; chronoFLO4, p = .04). Median survival was 20.7 mo in patients with G3-4 neutropenia versus 12.5 mo in neutropenia-free patients on FOLFOX2 (p < .0001). Corresponding figures were 13.7 and 19.4 mo, respectively, on chronoFLO4 (p = .36). Multivariate analysis confirmed occurrence of severe neutropenia independently predicted for better overall survival on FOLFOX2 (HR = 0.56; p = .015), and worse survival on chronoFLO4 (HR = 1.77, p = .06), with a significant interaction test (p < .0001). Prediction of better survival in neutropenic patients on FOLFOX2 supports the administration of conventional chemotherapy near maximum tolerated dose. The opposite trend shown here for chronoFLO4 supports the novel concept of jointly optimized hematologic tolerability and efficacy through personalized circadian-timed therapy.


Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Fluoruracila/uso terapêutico , Leucovorina/uso terapêutico , Neutropenia/induzido quimicamente , Compostos Organoplatínicos/uso terapêutico , Adulto , Idoso , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Relógios Biológicos/fisiologia , Ritmo Circadiano/fisiologia , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Metástase Neoplásica , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Prognóstico , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
19.
Anticancer Res ; 31(4): 1407-9, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21508393

RESUMO

AIM: To determine imatinib nonadherence rates in patients with gastrointestinal tumors (GIST) over 90 days. PATIENTS AND METHODS: A prospective 90-day observational, open-label, multicenter study was carried out of 28 evaluable GIST patients on imatinib. Nonadherence behavior was measured using a 4-item patient interview. Clinicians, patients, and collaterals rated perceived patient adherence on a 0-100 VAS scale. RESULTS: Nonadherence rates in the 4 weeks prior to baseline and follow-up were 29% (95% CI=26-32) and 24% (95% CI=21-27, p>0.05). Mean VAS ratings of perceived adherence ranged from 95.2 ± 10.2 to 97.3 ± 4.8 (p>0.05 for time and source of rating). Correlations between perceptions of and actual adherence behavior were negative. CONCLUSION: In this first study on imatinib nonadherence in GIST patients, rates were similar to those observed in patients with chronic myeloid leukemia, higher than clinically expected and exceeding meta-analytic estimates for cancer. Nonadherence rates were consistent across the 90-day period. Nonadherence behavior should be assessed by clinicians.


Assuntos
Tumores do Estroma Gastrointestinal/tratamento farmacológico , Adesão à Medicação , Recidiva Local de Neoplasia/tratamento farmacológico , Piperazinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Adolescente , Adulto , Benzamidas , Feminino , Seguimentos , Humanos , Mesilato de Imatinib , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Estudos Prospectivos , Proteínas Tirosina Quinases/antagonistas & inibidores , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
20.
BMC Cancer ; 10: 642, 2010 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-21092320

RESUMO

BACKGROUND: The use of chemotherapy regimens with moderate or high risk of febrile neutropenia (defined as having a FN incidence of 10% or more) and the respective incidence and clinical management of FN in breast cancer and NHL has not been studied in Belgium. The existence of a medical need for G-CSF primary and secondary prophylaxis with these regimens was investigated in a real-life setting. METHODS: Nine oncologists and six hematologists from different Belgian general hospitals and university centers were surveyed to collect expert opinion and real-life data (year 2007) on the use of chemotherapy regimens with moderate or high risk of febrile neutropenia and the clinical management of FN in patients aged <65 years with breast cancer or NHL. Data were retrospectively obtained, over a 6-month observation period. RESULTS: The most frequently used regimens in breast cancer patients (n = 161) were FEC (45%), FEC-T (37%) and docetaxel alone (6%). In NHL patients (n = 39), R-CHOP-21 (33%) and R-ACVBP-14 (15%) were mainly used. Without G-CSF primary prophylaxis (PP), FN occurred in 31% of breast cancer patients, and 13% had PSN. After G-CSF secondary prophylaxis (SP), 4% experienced further FN events. Only 1 breast cancer patient received PP, and did not experience a severe neutropenic event. Overall, 30% of chemotherapy cycles observed in breast cancer patients were protected by PP/SP. In 10 NHL patients receiving PP, 2 (20%) developed FN, whereas 13 (45%) of the 29 patients without PP developed FN and 3 (10%) PSN. Overall, 55% of chemotherapy cycles observed in NHL patients were protected by PP/SP. Impaired chemotherapy delivery (timing and/or dose) was reported in 40% (breast cancer) and 38% (NHL) of patients developing FN. Based on oncologist expert opinion, hospitalization rates for FN (average length of stay) without and with PP were, respectively, 48% (4.2 days) and 19% (1.5 days). Similar rates were obtained from hematologists. CONCLUSIONS: Despite the studied chemotherapy regimens being known to be associated with a moderate or high risk of FN, upfront G-CSF prophylaxis was rarely used. The observed incidence of severe neutropenic events without G-CSF prophylaxis was higher than generally reported in the literature. The impact on medical resources used is sizeable.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Febre/induzido quimicamente , Linfoma não Hodgkin/tratamento farmacológico , Neutropenia/induzido quimicamente , Centros Médicos Acadêmicos , Adulto , Idoso , Bélgica/epidemiologia , Neoplasias da Mama/epidemiologia , Feminino , Febre/epidemiologia , Febre/prevenção & controle , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Fidelidade a Diretrizes , Pesquisas sobre Atenção à Saúde , Hospitalização , Hospitais Gerais , Humanos , Incidência , Linfoma não Hodgkin/epidemiologia , Masculino , Pessoa de Meia-Idade , Neutropenia/epidemiologia , Neutropenia/prevenção & controle , Guias de Prática Clínica como Assunto , Padrões de Prática Médica , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
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