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1.
Breast Cancer Res Treat ; 153(3): 583-90, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26369533

RESUMO

Breast cancer patients with absent or reduced CYP2D6 activity and consequently low endoxifen levels may benefit less from tamoxifen treatment. CYP2D6 poor and intermediate metabolizers may need a personalized increased tamoxifen dose to achieve effective endoxifen serum concentrations, without increasing toxicity. From a prospective study population of early breast cancer patients using tamoxifen (CYPTAM: NTR1509), 12 CYP2D6 poor and 12 intermediate metabolizers were selected and included in a one-step tamoxifen dose escalation study during 2 months. The escalated dose was calculated by multiplying the individual's endoxifen level at baseline relative to the average endoxifen concentration observed in CYP2D6 extensive metabolizers by 20 mg (120 mg maximum). Endoxifen levels and tamoxifen toxicity were determined at baseline and after 2 months, just before patients returned to the standard dose of 20 mg. Tamoxifen dose escalation in CYP2D6 poor and intermediate metabolizers significantly increased endoxifen concentrations (p < 0.001; p = 0.002, respectively) without increasing side effects. In intermediate metabolizers, dose escalation increased endoxifen to levels comparable with those observed in extensive metabolizers. In poor metabolizers, the mean endoxifen level increased from 24 to 81 % of the mean concentration in extensive metabolizers. In all patients, the endoxifen threshold of 5.97 ng/ml (=16.0 nM) reported by Madlensky et al. was reached following dose escalation. CYP2D6 genotype- and endoxifen-guided tamoxifen dose escalation increased endoxifen concentrations without increasing short-term side effects. Whether such tamoxifen dose escalation is effective and safe in view of long-term toxic effects is uncertain and needs to be explored.


Assuntos
Antineoplásicos Hormonais/farmacologia , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Citocromo P-450 CYP2D6/genética , Genótipo , Tamoxifeno/análogos & derivados , Adulto , Idoso , Monitoramento de Medicamentos , Feminino , Humanos , Pessoa de Meia-Idade , Farmacogenética , Fenótipo , Estudos Prospectivos , Fatores de Risco , Tamoxifeno/farmacologia , Tamoxifeno/uso terapêutico , Resultado do Tratamento
2.
Ann Hematol ; 94(8): 1373-9, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25869027

RESUMO

Elderly patients with diffuse large B-cell lymphoma (DLBCL) are frequently not treated with standard immunochemotherapy, and this influences survival negatively. The purpose of this study was to gain more insight into treatment decision-making by hematologists. Case vignettes concerning patients with DLBCL were presented to hematologists in the Netherlands. Patient characteristics (age, comorbidity) differed per case. Respondents were asked in each case if they would treat the patient with curative intent by means of full-dose chemotherapy or chemotherapy with dose reduction or if they would not treat the patient with curative intent. The vast majority of respondents would treat an elderly patient diagnosed with DLBCL without a relevant medical history with full-dose chemotherapy irrespective of age. In the presence of comorbidity, lack of social support, cognitive disorders, and untreated depression dose reductions in advance are frequently applied or patients are not treated with curative intent. This is most pronounced for patients aged older than 80 years. Respondents working in a university hospital more frequently refrain form full-dose chemotherapy with curative intent compared to respondents working in tertiary medical teaching hospitals or general hospitals. Patients without a relevant medical history are generally treated with curative intent irrespective of age. Cognitive disorders, comorbidity, and depression reduce the change of being treated with curative intent. This is most prominent in the eldest patient category.


Assuntos
Antineoplásicos/administração & dosagem , Tomada de Decisões , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Papel do Médico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Linfoma Difuso de Grandes Células B/epidemiologia , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Resultado do Tratamento
3.
Neth J Med ; 72(3): 165-9, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24846934

RESUMO

BACKGROUND: Elderly patients with non-Hodgkin's lymphoma (NHL) are often not treated with standard immunochemotherapy and this might have a negative impact on their survival. Little is known about the determinants that play a role in treatment decision-making of clinicians regarding elderly patients with NHL. The objective of this study was to gain more insight into these determinants. METHODS: A survey was conducted amongst haematologists in the Netherlands. The survey contained questions about comorbidity, polypharmacy, social setting, nutritional status, depression, mild cognitive impairment, dementia, activities of daily living (ADL) and instrumental activities of daily living (IADL) in relation to treatment decisions in elderly NHL patients. RESULTS: Of all comorbidities, respondents designated cognitive disorders and cardiovascular comorbidity as the most important factors when assessing whether an older patient with NHL is eligible for curative treatment. Also in decreasing degree of importance ADL, IADL and depressive disorder are frequently included in treatment decision-making. Almost half of the respondents feel that treatment of the elderly person is complicated as a result of a lack of scientific evidence. CONCLUSION: Haematologists are aware of coexisting problems in elderly patients and they frequently take comorbidities, cognitive disorders and functional status into consideration in treatment decision-making. Future studies are needed to determine the exact role that these factors should play in the treatment of elderly patients. Furthermore, haematologists feel that treatment of the elderly is complicated and there is a lack of scientific evidence, and therefore older adults should be better represented in clinical trials.


Assuntos
Antineoplásicos/administração & dosagem , Hematologia , Linfoma não Hodgkin/complicações , Linfoma não Hodgkin/tratamento farmacológico , Padrões de Prática Médica , Atividades Cotidianas , Idoso , Doenças Cardiovasculares/complicações , Transtornos Cognitivos/complicações , Tomada de Decisões , Depressão/complicações , Feminino , Humanos , Nefropatias/complicações , Hepatopatias/complicações , Pneumopatias/complicações , Masculino , Pessoa de Meia-Idade , Limitação da Mobilidade , Países Baixos , Estado Nutricional , Polimedicação
4.
Ann Oncol ; 25(5): 998-1004, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24585721

RESUMO

BACKGROUND: The role of zoledronic acid (ZA) when added to the neoadjuvant treatment of breast cancer (BC) in enhancing the clinical and pathological response of tumors is unclear. The effect of ZA on the antitumor effect of neoadjuvant chemotherapy has not prospectively been studied before. PATIENTS AND METHODS: NEOZOTAC is a national, multicenter, randomized study comparing the efficacy of TAC (docetaxel, adriamycin and cyclophosphamide i.v.) followed by granulocyte colony-stimulating factor on day 2 with or without ZA 4 mg i.v. q 3 weeks inpatients withstage II/III, HER2-negative BC. We present data on the pathological complete response (pCR in breast and axilla), on clinical response using MRI, and toxicity. Post hoc subgroup analyses were undertaken to address the predictive value of menopausal status. RESULTS: Addition of ZA to chemotherapy did not improve pCR rates (13.2% for TAC+ZA versus 13.3% for TAC). Postmenopausal women (N = 96) had a numerical benefit from ZA treatment (pCR 14.0% for TAC+ZA versus 8.7% for TAC, P = 0.42). Clinical objective response did not differ between treatment arms (72.9% versus 73.7%). There was no difference in grade III/IV toxicity between treatment arms. CONCLUSIONS: Addition of ZA to neoadjuvant chemotherapy did not improve pathological or clinical response to chemotherapy. Further investigations are warranted in postmenopausal women with BC, since this subgroup might benefit from ZA treatment.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Receptor ErbB-2/metabolismo , Adulto , Idoso , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Ciclofosfamida/administração & dosagem , Difosfonatos/administração & dosagem , Docetaxel , Doxorrubicina/administração & dosagem , Feminino , Humanos , Imidazóis/administração & dosagem , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Estudos Prospectivos , Taxoides/administração & dosagem , Resultado do Tratamento , Ácido Zoledrônico
5.
Ann Oncol ; 25(3): 599-605, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24504445

RESUMO

BACKGROUND: Prospective data on chemotherapy for elderly patients with metastatic breast cancer (MBC) remain scarce. We compared the efficacy and safety of first-line chemotherapy with pegylated liposomal doxorubicin (PLD) versus capecitabine in MBC patients aged ≥65 years in a multicentre, phase III trial. PATIENTS AND METHODS: Patients were randomized to six cycles of PLD (45 mg/m(2) every 4 weeks) or eight cycles of capecitabine (1000 mg/m(2) twice daily, day 1-14 every 3 weeks). RESULTS: The study enrolled 78 of the planned 154 patients and was closed prematurely due to slow accrual and supply problems of PLD. Many included patients were aged ≥75 years (54%) and vulnerable (≥1 geriatric condition: 71%). The median dose intensity was 85% for PLD and 84% for capecitabine, respectively. In both arms, the majority of patients completed at least 12 weeks of treatment (PLD 73%; capecitabine 74%). After a median follow-up of 39 months, 77 patients had progressed and 62 patients had died of MBC. Median progression-free survival was 5.6 versus 7.7 months (P = 0.11) for PLD and capecitabine, respectively. Median overall survival was 13.8 months for PLD and 16.8 months for capecitabine (P = 0.59). Both treatments were feasible, grade 3 toxicities consisting of fatigue (both arms: 13%), hand-foot syndrome (PLD: 10%; capecitabine: 16%), stomatitis (PLD: 10%; capecitabine: 3%), exanthema (PLD: 5%) and diarrhoea (PLD: 3%; capecitabine: 5%). Only 1 of 10 patients aged ≥80 years completed chemotherapy, while 3 and 6 patients discontinued treatment due to toxicity or progressive disease, respectively. CONCLUSION: Both PLD and capecitabine demonstrated comparable efficacy and acceptable tolerance as first-line single-agent chemotherapy in elderly patients with MBC, even in vulnerable patients or patients aged ≥75 years. However, patients aged ≥80 years were unlikely to complete chemotherapy successfully. CLINICAL TRIAL NUMBERS: EudraCT 2006-002046-10; ISRCTN 11114726; CKTO 2006-09; BOOG 2006-02.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Desoxicitidina/análogos & derivados , Doxorrubicina/análogos & derivados , Fluoruracila/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Antibióticos Antineoplásicos/efeitos adversos , Antibióticos Antineoplásicos/farmacologia , Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/mortalidade , Capecitabina , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Intervalo Livre de Doença , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Metástase Neoplásica/tratamento farmacológico , Países Baixos , Polietilenoglicóis/efeitos adversos , Polietilenoglicóis/uso terapêutico , Estudos Prospectivos , Resultado do Tratamento
6.
Breast ; 23(1): 81-7, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24314824

RESUMO

AIM: To evaluate the association between baseline comprehensive geriatric assessment (CGA) or the Groningen Frailty Indicator (GFI) and toxicity in elderly metastatic breast cancer (MBC) patients treated with first-line palliative chemotherapy. PATIENTS AND METHODS: MBC patients (≥65 years) were randomized between pegylated liposomal doxorubicine or capecitabine. CGA included instrumental activities of daily living (IADL), cognition using the mini-mental state examination (MMSE), mood using the geriatric depression scale (GDS), comorbidity using the Charlson index, polypharmacy and nutritional status using the body mass index. Frailty on CGA was defined as one or more of the following: IADL ≤ 13, MMSE ≤ 23, GDS ≥ 5, BMI ≤ 20, ≥5 medications or Charlson ≥2. The cut-off for frailty on the GFI was ≥4. RESULTS: Of the randomized 78 patients (median age 75.5 years, range 65.8-86.8 years), 73 were evaluable for CGA; 52 (71%) had one or more geriatric conditions. Grade 3-4 chemotherapy-related toxicity was experienced by 19% of patients without geriatric conditions compared to 56% of patients with two geriatric conditions and 80% of those with three or more (p = 0.002). Polypharmacy was the only individual factor significantly associated with toxicity (p = 0.001). GFI had a sensitivity of 69% and a specificity of 76% for frailty on CGA, and was not significantly associated with survival or toxicity. CONCLUSION: In this study of elderly patients with MBC, the number of geriatric conditions correlated with grade 3-4 chemotherapy-related toxicity. Therefore, in elderly patients for whom chemotherapy is being considered, a CGA could be a useful addition to the decision-making process.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Desoxicitidina/análogos & derivados , Doxorrubicina/análogos & derivados , Fluoruracila/análogos & derivados , Avaliação Geriátrica , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Índice de Massa Corporal , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Capecitabina , Transtornos Cognitivos/epidemiologia , Comorbidade , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Depressão/epidemiologia , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Fadiga/induzido quimicamente , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Idoso Fragilizado , Síndrome Mão-Pé/etiologia , Humanos , Entrevista Psiquiátrica Padronizada , Cuidados Paliativos , Polietilenoglicóis/efeitos adversos , Polietilenoglicóis/uso terapêutico , Polimedicação , Fatores de Risco , Estomatite/induzido quimicamente , Resultado do Tratamento
7.
Breast ; 22(5): 753-60, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23414850

RESUMO

INTRODUCTION: The prognostic value of geriatric assessment in older patients with breast cancer treated with chemotherapy is largely unknown. METHODS: Fifty-five patients with advanced breast cancer aged 70 years or older were assessed by Mini Nutritional Assessment (MNA), Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), Groningen Frailty Indicator (GFI) and Mini Mental State Examination (MMSE). Levels of albumin, hemoglobin, creatinine and lactate dehydrogenase were measured. Patients completing at least four cycles of chemotherapy were reassessed by GFI and MMSE and mortality was evaluated using Cox regression analysis. RESULTS: The mean age was 76 year (SD 4.8). Inferior MNA and GFI scores were associated with increased hazard ratios for mortality: 3.05 (95% confidence interval [CI]: 1.44-6.45; p = 0.004) and 3.40 (95% CI: 1.62-7.10; p = 0.001), respectively. Physical aspects of frailty worsened during the course of chemotherapy. Laboratory values were not associated with assessment scores nor were they predictive for mortality. CONCLUSIONS: Malnutrition and frailty, rather than cognitive impairment and laboratory values, were associated with an increased mortality risk in these elderly breast cancer patients with advanced breast cancer.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Avaliação Geriátrica , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Neoplasias da Mama/sangue , Neoplasias da Mama/complicações , Neoplasias da Mama Masculina/sangue , Neoplasias da Mama Masculina/tratamento farmacológico , Neoplasias da Mama Masculina/mortalidade , Transtornos Cognitivos/complicações , Creatinina/sangue , Feminino , Hemoglobinas/metabolismo , Humanos , Estimativa de Kaplan-Meier , L-Lactato Desidrogenase/sangue , Masculino , Desnutrição/complicações , Prognóstico , Modelos de Riscos Proporcionais , Albumina Sérica/metabolismo
8.
Breast ; 22(4): 556-9, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23305962

RESUMO

BACKGROUND: In a Dutch multicentre study, elderly (65 + year) metastatic breast cancer patients, eligible for first-line chemotherapy, were randomised between two types of single-agent chemotherapy. As accrual was slow, with 78 randomised patients between April 2007 and September 2011, we explored potential barriers in the accrual process and their consequences for characteristics of included patients. METHODS: We sent surveys on the reasons for non-inclusion to all coordinating investigators. We also examined inclusion in a concurrent, non-elderly breast cancer study of the trialists' group and analysed baseline geriatric characteristics of included patients. RESULTS: Investigators from fifteen participating centres returned the survey. Most commonly reported barriers to inclusion were: patient's refusal of chemotherapy (n = 8) or of randomisation (n = 9), impaired cognition (n = 3) and insufficient cardiac function (n = 2). Oncologists' preference for combination regimens over single-agent chemotherapy was reported twice. Twenty-eight potentially eligible patients, aged 65-71 years, were included in a concurrent, study investigating combination chemotherapy in fit non-elderly patients with metastatic breast cancer. However, baseline characteristics of the included patients showed that the OMEGA study succeeded in including frail and older patients, with a performance status of 2 in 22% of patients and 54% of patients aged 75 years or older. CONCLUSION: Accrual in this study was mainly hampered by patient's refusal or preference for a particular type of treatment, and an overall condition considered as too fit or too frail for inclusion. Future trials in elderly metastatic breast cancer patients should focus on non-restrictive inclusion criteria as well as on education of physicians and elderly patients on the advantages of trial participation.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Seleção de Pacientes , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Feminino , Humanos , Países Baixos , Recusa do Paciente ao Tratamento
9.
Eur J Surg Oncol ; 38(2): 110-7, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22172646

RESUMO

AIMS: The aim of this study was to investigate non-compliance to aromatase inhibitors and factors associated with early treatment discontinuation in the extended adjuvant setting. METHODS: The IDEAL trial is a prospective, open-label phase-III trial comparing 2.5 with 5 years of extended adjuvant letrozole (LET) in hormone receptor positive (HR+) postmenopausal early breast-cancer patients after 5 years of adjuvant endocrine therapy (ET). The purpose of this study was to assess non-compliance in the first 2.5 years of extended adjuvant therapy. Non-compliance was defined as early discontinuation of LET for all reasons, excluding death or recurrence. RESULTS: At 2.5 years, 1215 patients were included in the analysis. Overall non-compliance probability was 18.4%, of which 85.1% discontinued due to toxicities. Analyses showed that patients with prior sequential therapy were less likely to discontinue treatment than when treated with AI or TAM upfront (logrank p = 0.004). Longer treatment-free intervals also predicted more non-compliance (logrank p = 0.011). Age was not predictive of non-compliance (p = 0.571). Prior surgery (mastectomy vs breast conserving surgery), both with or without radiotherapy and/or chemotherapy were also not associated with early treatment discontinuation (p = 0.228 and p = 0.585 respectively). Although having fewer than four positive lymph nodes predicted more non-compliance (logrank p = 0.050), age, tumor type and locoregional treatment did not. CONCLUSIONS: High non-compliance to extended ET was confirmed. Toxicities were the major reason for discontinuation, and this was not influenced by age. Longer treatment-free intervals and fewer positive lymph nodes predicted more non-compliance. Patients who underwent sequential therapy were least likely to discontinue extended adjuvant ET.


Assuntos
Antineoplásicos Hormonais/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Nitrilas/uso terapêutico , Cooperação do Paciente/estatística & dados numéricos , Triazóis/uso terapêutico , Adulto , Idoso , Antineoplásicos Hormonais/efeitos adversos , Neoplasias da Mama/mortalidade , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Intervalos de Confiança , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Letrozol , Assistência de Longa Duração , Mastectomia Segmentar , Dose Máxima Tolerável , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Nitrilas/efeitos adversos , Estudos Prospectivos , Medição de Risco , Estatísticas não Paramétricas , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Triazóis/efeitos adversos
10.
Crit Rev Oncol Hematol ; 79(2): 205-12, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20709565

RESUMO

INTRODUCTION: Comprehensive geriatric assessment (CGA) gives useful information on the functional status of older cancer patients. However, its meaning for a proper selection of elderly patients before chemotherapy and, even more important, the influence of chemotherapy on the outcome of geriatric assessment is unknown. METHODS: 202 cancer patients, for whom an indication for chemotherapy was made by the medical oncologist, underwent a GA before start of chemotherapy by Mini Nutritional Assessment (MNA), Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), Groningen Frailty Index (GFI) and Mini Mental State Examination (MMSE). After completion of a minimum of four cycles of chemotherapy or at 6 months after the start of chemotherapy the GFI and MMSE assessment was repeated. RESULTS: Frailty was shown in 10% of patients by means of MMSE, 32% by MNA, 37% by GFI and in 15% by IQCODE. Compared to patients who received 4 or more cycles of chemotherapy, the MNA and MMSE scores were significantly lower for patients treated with less than 4 cycles (p = 0.001 and p = 0.04 respectively). The mortality rate after start of chemotherapy was increased for patients with low MNA and high GFI scores with hazard ratios of 2.19 (95% confidence interval [CI]: 1.42-3.39; p < 0.001) and 1.80 (95% CI: 1.17-2.78; p = 0.007), respectively. After adjusting for sex, age, purpose of chemotherapy and type of malignancy these hazard ratios remained significant (p < 0.001 and p = 0.004), respectively. Finally, for the 51 patients who underwent repeated post-chemotherapy evaluation by GFI and MMSE, a statistically significant deterioration for the MMSE (p = 0.041) was found but not for the GFI. CONCLUSIONS: Both inferior MNA and MMSE scores increased the probability not to complete chemotherapy. Also, an inferior score for MNA and GFI showed an increased mortality risk after the start of chemotherapy. The mean MMSE score worsened significantly during chemotherapy.


Assuntos
Antineoplásicos/uso terapêutico , Avaliação Geriátrica , Neoplasias/tratamento farmacológico , Atividades Cotidianas/psicologia , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Cognição/fisiologia , Feminino , Idoso Fragilizado , Avaliação Geriátrica/métodos , Humanos , Masculino , Neoplasias/mortalidade , Neoplasias/patologia , Avaliação Nutricional , Valor Preditivo dos Testes , Projetos de Pesquisa , Fatores de Risco , Inquéritos e Questionários , Análise de Sobrevida
11.
Ann Oncol ; 21(5): 974-82, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-19875752

RESUMO

BACKGROUND: The Tamoxifen and Exemestane Adjuvant Multinational (TEAM) trial investigates the efficacy and safety of adjuvant exemestane alone and in sequence after tamoxifen in postmenopausal women with hormone-sensitive early breast cancer. As there was a nationwide participation in The Netherlands, we studied the variations in patterns of care in the Comprehensive Cancer Centre Regions (CCCRs) and compliance with national guidelines. METHODS: Clinicopathological characteristics, carried out local treatment strategies and adjuvant chemotherapy data were collected. RESULTS: From 2001 to January 2006, 2754 Dutch patients were randomised to the study. Mean age of patients was 65 years (standard deviation 9). Tumours were < or =2 cm in 46% (within CCCRs 39%-50%), node-negative disease varied from 25% to 45%, and PgR status was determined in 75%-100% of patients. Mastectomy was carried out in 55% (45%-70%), sentinel lymph node procedure in 68% (42%-79%) and axillary lymph node dissections in 77% (67%-83%) of patients, all different between CCCRs (P < 0.0001). Adjuvant chemotherapy was given in 15%-70% of eligible patients (P < 0.001). DISCUSSION: In spite of national guidelines, breast cancer treatment on specific issues widely varied between the various Dutch regions. These data provide valuable information for breast cancer organisations indicating (lack of) guideline adherence and areas for breast cancer care improvement.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Pós-Menopausa , Padrões de Prática Médica , Idoso , Androstadienos/administração & dosagem , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Terapia Combinada , Feminino , Humanos , Agências Internacionais , Pessoa de Meia-Idade , Neoplasias Hormônio-Dependentes/patologia , Neoplasias Hormônio-Dependentes/cirurgia , Guias de Prática Clínica como Assunto , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Estudos Retrospectivos , Taxa de Sobrevida , Tamoxifeno/administração & dosagem , Resultado do Tratamento
12.
Neth J Med ; 67(10): 353-5, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19915230

RESUMO

A 35-year-old man presented at the outpatient department of pulmonary diseases with fever, rhinitis and coughing. He had recently been on holiday in California. Except for a body temperature of 39.7 degrees C there were no other abnormal findings at the physical examination. Chest X-ray showed a consolidation in the left upper lobe. Under antibiotic treatment his clinical condition deteriorated. Coccidioidomycosis was the suspected diagnosis and confirmed by the results of CT scanning and culture of bronchoalveolar lavage fluid. Treatment with itraconazole resulted in lasting improvement. The case stipulates the importance of travel history.


Assuntos
Coccidioidomicose/diagnóstico , Pneumopatias Fúngicas/diagnóstico , Viagem , Adulto , Antifúngicos/uso terapêutico , Líquido da Lavagem Broncoalveolar , California , Coccidioidomicose/tratamento farmacológico , Coccidioidomicose/etiologia , Clima Desértico , Humanos , Itraconazol/uso terapêutico , Pneumopatias Fúngicas/tratamento farmacológico , Pneumopatias Fúngicas/etiologia , Masculino , Países Baixos , Tomografia Computadorizada por Raios X , Falha de Tratamento
13.
Neth J Med ; 67(8): 355-8, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19767667

RESUMO

BACKGROUND: To determine whether the reported increase in survival of patients with diffuse large B-cell malignant lymphoma (DLBCL) after the introduction of rituximab is also seen in a non-academic hospital in the Netherlands. A retrospective study. METHODS: A dataset was made containing all newly diagnosed patients with DLBCL in a period of 2.5 years before until 2.5 years after introduction of rituximab in the standard treatment. Total follow-up time was 6.5 years with a minimal follow-up of 18 months. RESULTS: The study population consisted of 65 patients; 32 in the prerituximab group (median follow-up time 60 months) and 33 in the postrituximab group (median follow-up time 29 months). Progression-free survival increased significantly in the postrituximab group (hazard ratio 0.31; 95% CI 0.12 to 0.78; p=0.013; log rank p=0.008). The overall survival also showed a significant increase (p=0.048). The 18-month progression-free survival increased from 59.4 to 81.8%; the overall survival at 18 months showed an increase from 65.5 to 81.8%. CONCLUSION: The introduction of rituximab in the treatment of DLB CL with CHOP chemotherapy has resulted in a significantly better prognosis for patients with DLBCL, treated in the Reinier de Graaf Gasthuis in Delft.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Intervalos de Confiança , Ciclofosfamida/administração & dosagem , Bases de Dados Factuais , Progressão da Doença , Doxorrubicina/administração & dosagem , Feminino , Frequência Cardíaca , Humanos , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/radioterapia , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prognóstico , Radioterapia Adjuvante , Estudos Retrospectivos , Rituximab , Fatores de Tempo , Vincristina/administração & dosagem
14.
Ned Tijdschr Geneeskd ; 152(11): 606-14, 2008 Mar 15.
Artigo em Holandês | MEDLINE | ID: mdl-18410020

RESUMO

An 82-year-old man was admitted with a 1-week history of chilling fever and dry cough. Laboratory tests revealed pancytopenia and elevated levels of C-reactive protein and lactic dehydrogenase (LDH). Screening for infectious diseases was negative. A bone marrow biopsy showed aspecific findings. The combination of pancytopenia, persistent fever, elevated LDH and hepatomegaly (demonstrated by ultrasound examination of the abdomen) was suggestive of the haemophagocytic syndrome. This was confirmed by very high levels of ferritin and soluble interleukin-2 receptor in the blood. In addition, re-examination of the bone marrow showed several haemophagocytic histiocytes. A polymerase chain reaction for Epstein-Barr virus (EBV) revealed a very high viral load. Since the patient had a history of an increased level of anti-EBV immunoglobulin-G, this was explained by a reactivation of the EBV infection. On the sixth day in hospital the patient developed signs of bilateral pneumonia and subsequent multiple organ failure. Despite intensive treatment the patient died. Autopsy revealed no haematological or other malignancies, but did show haemophagocytosis in many organs. It was then concluded that the patient had a virus-associated haemophagocytic syndrome, due to a reactivation of EBV, for which no underlying cause was found.


Assuntos
Infecções por Vírus Epstein-Barr/diagnóstico , Herpesvirus Humano 4/isolamento & purificação , Linfo-Histiocitose Hemofagocítica/diagnóstico , Idoso de 80 Anos ou mais , Proteína C-Reativa/análise , Infecções por Vírus Epstein-Barr/sangue , Infecções por Vírus Epstein-Barr/complicações , Evolução Fatal , Febre de Causa Desconhecida/etiologia , Humanos , Linfo-Histiocitose Hemofagocítica/sangue , Linfo-Histiocitose Hemofagocítica/complicações , Masculino , Pancitopenia/etiologia
15.
Neth J Med ; 65(11): 448-51, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18079568

RESUMO

Analysis of an 83-year-old male presenting with diarrhoea showed secretory diarrhoea. serum levels of gastrin and pancreatic polypeptide were elevated. Somatostatin-receptor scintigraphy revealed a hot spot in the left thoracic wall and subsequently, breast adenocarcinoma with neuroendocrine differentiation was diagnosed. Postoperatively, the patient made an uneventful recovery. The relationship between the clinical picture, the results of pathological examination and hormonal analysis is discussed and put into perspective.


Assuntos
Neoplasias da Mama/patologia , Diarreia/etiologia , Idoso de 80 Anos ou mais , Neoplasias da Mama/complicações , Gastrinas , Humanos , Masculino , Tumores Neuroendócrinos/complicações , Tumores Neuroendócrinos/patologia , Polipeptídeo Pancreático
16.
Neth J Med ; 62(6): 198-200, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15460500

RESUMO

We describe a 68-year-old woman with an episode of diarrhoea, malaise and weight loss, caused by infection with Cryptosporidium. The diagnosis was hampered because this patient had a low risk of HIV infection, a two-year history of Crohn's disease, and a simultaneous candidal infection. An infection with Cryptosporidium was demonstrated with electron microscopic examination, and subsequent tests revealed positive HIV serology. AIDS was probably contracted through her husband.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Criptosporidiose/diagnóstico , Idoso , Feminino , Humanos , Achados Incidentais
17.
Leuk Lymphoma ; 45(1): 101-7, 2004 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15061204

RESUMO

The prognostic significance of age was studied in 372 patients with diffuse large B-cell non-Hodgkin's lymphoma, in relation to the prognostic factors of overexpressed BCL2 and p53 oncoprotein. Overexpression of BCL2 and p53 oncoprotein was defined when more than 50% of the tumor cells showed positive staining. The data were analyzed with respect to the age groups < 65 and > or = 65 years of age. There was a trend for BCL2 overexpression to occur significantly more often among patients older than 65 years of age (P = 0.065). Patients with BCL2 overexpression showed significantly inferior disease free survival rate, but only for patients younger than 65 years (log-rank test P = 0.0002), and the overexpression showed also an independent prognostic significance (P < 0.001). With respect to overexpressed p53 a significant difference was reached for complete remission rate (P = 0.01) and 5-year survival rate (log-rank test P = 0.04), again only for the younger age group. When the analyses were repeated for the older patients who had been treated adequately, the same lack of significance was found, both for BCL2 and p53. This study demonstrates that the negative prognostic value of overexpressed BCL2 and p53 protein is not of concern for patients older than 65 years of age. Among elderly patients the International Prognostic Index score seems the predominant risk factor for inferior prognosis.


Assuntos
Idoso , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Sistema de Registros , Proteína Supressora de Tumor p53/metabolismo , Intervalo Livre de Doença , Humanos , Imuno-Histoquímica , Linfoma Difuso de Grandes Células B/patologia , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida
18.
Ned Tijdschr Geneeskd ; 147(43): 2089-94, 2003 Oct 25.
Artigo em Holandês | MEDLINE | ID: mdl-14619195

RESUMO

Three patients, a girl aged 10 and two women aged 59 and 64 years, had erythema multiforme, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), respectively. SJS and TEN are rare illnesses with a high morbidity and mortality. The aetiology is mainly iatrogenic: a hypersensitivity reaction to certain pharmaceutical prescriptions. SJS and TEN should be differentiated from the more frequent erythema multiforme, a self-limiting disease without important residual symptoms, which is usually initiated by infection with herpes simplex virus. SJS and TEN are variants in a spectrum of exfoliative dermatoses with epidermal necrosis. SJS and TEN on the one hand and erythema multiforme on the other can be distinguished on the basis of aetiology, clinical symptoms and histopathology. The distinction can, however, be difficult, notably in the early stages. The girl recovered completely. The first woman was treated with corticosteroids and also recovered; she was thought to have developed the syndrome as a reaction to malarial prophylactics. The third patient died, despite extensive treatment, of multiorgan failure and sloughing of 70% of the skin, probably as a reaction to amoxicillin given for pneumococcal pneumonia.


Assuntos
Eritema Multiforme/diagnóstico , Síndrome de Stevens-Johnson/diagnóstico , Criança , Diagnóstico Diferencial , Eritema Multiforme/patologia , Eritema Multiforme/terapia , Evolução Fatal , Feminino , Humanos , Doença Iatrogênica , Pessoa de Meia-Idade , Prognóstico , Síndrome de Stevens-Johnson/patologia , Síndrome de Stevens-Johnson/terapia
19.
Ann Hematol ; 82(11): 661-70, 2003 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12923662

RESUMO

With rising age the incidence of non-Hodgkin's lymphoma (NHL), together with the fact that the proportion of people older than 65 years in Western populations will double during the next 40 years, poses the challenge to adequately meet the needs of elderly patients. After a general introduction on cancer in the elderly, a review is given concerning aspects of epidemiology and prognostic factors of NHL. Therapeutic strategies, including the use of hematopoietic growth factors, for the elderly with aggressive NHL are discussed. The future role for so-called comprehensive geriatric assessment (CGA) to appropriately determine treatment possibilities is emphasized. Much scientific work has to be performed before the true value of CGA instruments can be acknowledged. Screening instruments are discussed and the role for specially trained oncology nurses in the assessment process is stipulated.


Assuntos
Linfoma não Hodgkin/epidemiologia , Linfoma não Hodgkin/terapia , Idoso , Avaliação Geriátrica/métodos , Fatores de Crescimento de Células Hematopoéticas/uso terapêutico , Humanos , Linfoma não Hodgkin/mortalidade , Linfoma não Hodgkin/patologia , Estadiamento de Neoplasias , Prognóstico , Radioimunoterapia
20.
Ann Oncol ; 13(8): 1275-84, 2002 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12181252

RESUMO

BACKGROUND: The influence of age on the outcome of follicular non-Hodgkin's lymphoma (FL) was studied in a population-based non-Hodgkin's lymphoma registry. PATIENTS AND METHODS: This study comprised 214 follicular lymphoma patients. Grade I/II was considered separately from grade III FL. The data were analyzed with respect to three age groups: <60, 60-69 and >or=70 years. RESULTS: The overall survival rate decreased in the older age groups. Grade III patients showed a statistically significant decrease in overall survival in comparison with grade I/II patients (P = 0.03). Cause-specific survival analysis showed that in the older age groups, there was an increasing influence of concomitant disease on the death rate, especially among grade III FL patients >70 years of age. The survival curve in grade III FL patients was shown to reach a plateau. The prognostic scoring system, according to the Italian Lymphoma Intergroup, fitted better to grade I/II patients, while the International Prognostic Index showed better discrimination amongst grade III patients. CONCLUSIONS: Separate grading for follicular lymphoma is useful. An age >70 years has a negative impact on outcome, but the contribution of concomitant disease herein is important. Different prognostic scoring systems should be applied to the different grades of FL.


Assuntos
Linfoma Folicular/epidemiologia , Sistema de Registros , Fatores Etários , Idoso , Estudos de Coortes , Feminino , Humanos , Incidência , Itália/epidemiologia , Linfoma Folicular/patologia , Linfoma Folicular/terapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Vigilância da População , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida
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