RESUMO
OBJECTIVES: Most research addressing needs and concerns of young patients with breast cancer (≤40 years) is retrospective. The HOHO European protocol is a prospective multicenter cohort study of young women with newly diagnosed breast cancer, about fertility, psychosocial and quality of life concerns. Here we report the baseline data and focus on predictors of fertility concerns. MATERIALS AND METHODS: Patient surveys and medical record review were used. The baseline survey included sociodemographic, medical and treatment data as well as questions on fertility concerns and preservation strategies. Subscales from the CAncer Rehabilitation Evaluation System-Short Form (CARES-SF) were administered to measure specific quality of life aspects. Uni- and multivariable modeling were used to investigate predictors of greater fertility concern. RESULTS: Among 297 eligible respondents, 67% discussed fertility issues before starting therapy, 64% were concerned about becoming infertile after treatment, and 15% decided not to follow prescribed therapies. Fifty-four percent of women wished future children before diagnosis; of these, 71% still desired biologic children afterwards. In multivariable analysis, not having children was the only patient characteristic significantly associated with fertility concerns at diagnosis. Twenty-seven percent used fertility preservation strategies. Women who received chemotherapy reported greater physical (pâ¯=â¯0.021) and sexual difficulties (pâ¯=â¯0.039) than women who did not. Women who were married or had a partner reported less psychosocial problems than single women (pâ¯=â¯0.039). CONCLUSIONS: Young women with newly diagnosed breast cancer have several concerns, including, but not limited to, fertility. The HOHO European study provides valuable information to develop targeted interventions.
Assuntos
Neoplasias da Mama/diagnóstico , Tomada de Decisões , Preservação da Fertilidade/psicologia , Preservação da Fertilidade/estatística & dados numéricos , Qualidade de Vida , Adulto , Fatores Etários , Neoplasias da Mama/psicologia , Neoplasias da Mama/terapia , Estudos de Coortes , Europa (Continente) , Feminino , Humanos , Itália , Estudos Longitudinais , Estudos Prospectivos , Medição de Risco , Inquéritos e Questionários , Suíça , Estados UnidosRESUMO
The differences in the number and duration of hospital stays of cancer patients in an advanced stage of disease were to be examined with regard to the most frequent cancer diagnoses. Therefore, routinely compiled data of the largest health insurance company in the State of Lower Saxony, Germany, were analysed. Patients with lung, colon, breast and prostate cancer were included, who died in the year of 2004. The parameters of frequency (case numbers) and duration (days) of inpatient hospital stays were examined for the 5-year period of 2000-2004, with special focus on the years 2003/2004. 355 patients were included. On average, the number of inpatient hospital stays amounted to 2.7 cases and 29 days per patient. 87.5% of the hospital stays within the study period occurred in 2003/2004. The patient groups differed significantly both in the average number of cases and in the duration of hospital stays (Kruskal-Wallis test: P<0001), whereby patients with lung cancer underwent inpatient hospital treatment most frequently (3.3 times), and for the longest periods (35 days). This study shows that patients in an advanced stage of lung cancer are a particular important target group for reducing hospitalization at the end of life. They should receive special attention when structures of palliative care are extended.
Assuntos
Tempo de Internação/estatística & dados numéricos , Neoplasias/terapia , Cuidados Paliativos/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/mortalidade , Estatística como Assunto , Assistência Terminal/estatística & dados numéricosRESUMO
Palliative care can be considered a holistic care approach for patients faced with incurable and progressive diseases in their last period of life. In this context, structural, cultural and content-related deficits are increasingly taken into account in the German health care system, however, there is a lack of scientific data. Therefore, it was the objective of an expert team at Hannover Medical School to analyse the current situation of palliative care in Lower Saxony from the perspective of health system research and to give recommendations for its further development, based on empirical studies in Lower Saxony and on a systematic national and international literature review. The study revealed that the main shortcomings were an unclear structuring and an inadequate definition with respect to other areas of care, a fundamental lack of integration in regard of routine processes of care and a lack of thorough tools for needs assessments. Therefore, a concept for the integration of palliative care in the care processes of cancer patients was developed and the specific need for hospice beds in regional districts was calculated by using parameters representing provision-related and epidemiological/demographic conditions. In comparison to current structures, an assessment of over- and undersupply as well as specific recommendations how to optimize palliative care were provided for politicians, payers and providers in Lower Saxony.
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Necessidades e Demandas de Serviços de Saúde/organização & administração , Modelos Organizacionais , Programas Nacionais de Saúde/organização & administração , Avaliação das Necessidades/organização & administração , Neoplasias/terapia , Cuidados Paliativos/organização & administração , Alocação de Recursos/organização & administração , Alemanha , HumanosAssuntos
Testes Genéticos/métodos , Transtornos da Audição/diagnóstico , Transtornos da Audição/genética , Testes Auditivos/métodos , Triagem Neonatal/métodos , Triagem Neonatal/organização & administração , Alemanha , Transtornos da Audição/congênito , Testes Auditivos/normas , Humanos , Lactente , Recém-Nascido , Guias de Prática Clínica como Assunto , Padrões de Prática Médica/normasRESUMO
In Germany, congenital hearing disorders are usually detected too late resulting in insufficient therapy of the disorder. To investigate these problems, the Federal Ministry of Health and the principal associations of statutory health insurance commissioned a pre-operative study. The study's aim is to verify whether introduction of a universal new-born hearing screening results in earlier diagnosis of hearing disorders and thus improves medical care for children with impaired hearing. Feasibility, effectiveness and economic tenability of this hearing screening programme will be investigated. The study is realised in the Hanover region and aims at carrying out a hearing test in all new-born during the first days of life. The tests will be performed in all 10 birth clinics and 2 paediatric clinics in the relevant region and in 24 otolaryngological practices. Hearing ability is controlled via an automated screening device measuring otoacoustic emissions. Sensitivity and specificity of the test is more than 95%. Economical feasibility is investigated by cost-effectiveness analyses. During a 6-month period the screening has been implemented in all clinics in every day routine. The mean coverage rate in the clinics has been stabilised to 97% of the total number. 4.7% of the children were presumed to suffer from unilateral hearing disorders and 2.3% from bilateral. In 13 cases the diagnosis of hearing disorder was confirmed. The mean age of diagnosis in these children was 3.7 months. The average age of therapy onset was 4.4 months. According to the present experience, area-wide implementation of hearing screening seems feasible in existing health care structures. The intention to advance the time of diagnosis and the therapy onset can be achieved by this method. Systematic training, introduction and quality assurance measures of screening are mandatory. Tracking of suspicious cases is necessary, even if it challenges data privacy regulations.
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Transtornos da Audição/congênito , Modelos Teóricos , Triagem Neonatal , Emissões Otoacústicas Espontâneas , Análise Custo-Benefício/estatística & dados numéricos , Estudos de Viabilidade , Feminino , Alemanha , Implementação de Plano de Saúde/economia , Transtornos da Audição/economia , Transtornos da Audição/prevenção & controle , Humanos , Lactente , Recém-Nascido , Masculino , Triagem Neonatal/economiaRESUMO
Recent developments in our ability to predict breast cancer risk necessitates primary care physicians learn to evaluate breast cancer risk and its importance in shaping decisions concerning surveillance and risk reduction measures. This article reviews the current opinion on risk assessment and management of women with an increased risk of breast/ovarian cancer. Management options are given for women at slightly, moderately and highly elevated breast cancer risk, as well as for BRCA1/2 carriers, based on currently available evidence.
Assuntos
Neoplasias da Mama/prevenção & controle , Neoplasias Ovarianas/prevenção & controle , Comportamento de Redução do Risco , Neoplasias da Mama/genética , Medicina Baseada em Evidências , Feminino , Genes BRCA1/fisiologia , Genes BRCA2/fisiologia , Humanos , Mamografia , Neoplasias Ovarianas/genéticaRESUMO
BACKGROUND: Atopic dermatitis (AD) is a common skin disease in childhood. Micro- and macro-environmental factors have not yet been studied simultaneously in a large cohort of the same area in detail. OBJECTIVES: The incidence of AD was investigated in 97% of all school entrants (n = 4219) in the city of Hannover, Germany, with regard to the influence of individual and environmental factors. METHODS: A standardized questionnaire based on the criteria of Hanifin and Rajka that has the sensitivity and specificity of 97% compared with the clinical diagnosis of a dermatologist and a logistic regression model were used. Multiple local-based environmental factors were analysed for all 49 city quarters. RESULTS: Of all children studied, 10.5% suffered from AD at some time in their lives. The frequency of AD was significantly increasing with more privileged socio-economic status (P < 0.01). Independent factors that were associated with a higher frequency of AD were German nationality (12.4% AD compared with 2.1% in non-German), higher paternal socio-economic status (i.e. father's profession), higher daily duration of the fathers' professional work and the lack of paternal shift work. In contrast, there was no significant association between the frequency of AD and local environmental factors such as the biological effective level of air pollution and urbanization. CONCLUSIONS: In conclusion, we confirm an association between a privileged life-style and a higher incidence of AD in a large number of investigated children between 5 and 9 years of age (97.6% of children were 6 or 7 years old) for the German city of Hannover. We propose the socio-economic status as a marker for different life-styles and social micro-environments in further studies as there were multiple significant correlations between individual social and environmental factors. The macro-environment seems to be less important for the disease outcome in this context.
Assuntos
Dermatite Atópica/etiologia , Meio Ambiente , Estilo de Vida , Criança , Dermatite Atópica/epidemiologia , Feminino , Alemanha/epidemiologia , Humanos , Incidência , Modelos Logísticos , Masculino , Análise Multivariada , Fatores de Risco , Classe Social , Fatores SocioeconômicosRESUMO
Anorexia and bulimia are relatively rare psychogenic illnesses, which nevertheless are of great concern for society since they affect a mostly very young population and are accompanied by a significantly raised mortality risk. This cost-of-illness analysis for eating disorders in Germany considers hospitalization, rehabilitation services, and indirect costs through inability to work and premature death. The cost estimates are based on projections derived from benefit data as listed by health insurance schemes and pension insurance schemes and from epidemiological studies on the prevalence of eating disorders and mortality rates. For anorexia the cost of illness amounts to approximately 195 million euros (73 direct costs and 122 mortality costs, for bulimia it comes to around 124 million euros (12 direct costs and 112 mortality costs). The annual cost per anorexia and bulimia patient is approximately 5,300 and 1,300 euros, respectively. This cost-of-illness analysis underlines the significance of indirect costs due to premature death, but also highlights the extremely cost-intensive treatment. The hospitalization cost of 12,800 euros per anorexia patient is markedly higher than the average hospitalization cost of 3,600 euros.
RESUMO
Chemoprevention of breast cancer, a dream? In one American study (National Surgical Adjuvant Breast and Bowel Project, NSABP-P1) tamoxifen decreased the incidence of invasive and non-invasive breast cancer, whereas in two English and Italian studies, it did not reduce this risk. Differences in the study population for the trials may underly these conflicting findings. New drugs, the SERMs, may be more promising.
Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/prevenção & controle , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Tamoxifeno/uso terapêutico , Adulto , Idoso , Austrália , Quimioprevenção , Europa (Continente) , Feminino , Humanos , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Estados UnidosRESUMO
BACKGROUND AND OBJECTIVE: Despite eager public interest there have been few significant studies about the views of the German population on active euthanasia. It was our purpose to investigate, before undertaking a representative enquiry about this controversial and ethically sensitive topic, to what extent public opinion and the underlying norms, values and preferences can be adequately obtained by standardized data collection. COHORT AND METHODS: An interdisciplinary project group established a standardized written form of enquiry for measuring public opinion about active euthanasia. The test was performed on an anonymized convenience [corrected] sample of 110 persons living in North Germany. The questionnaires consisted of ten hypothetical cases, 11 potentially relevant viewpoints on likely decisions and eight frequently expressed arguments used in the debate for and against euthanasia. RESULTS: The reply rate to the questionnaire was 89% (n = 98; 37 men and 59 women, average age 39.5 [21-81] years). Agreement with active euthanasia in the various case examples ranged, according to context, from 85 to 93%. Active euthanasia was accepted by a clear majority, if preconditions of a voluntary decision by a mentally sound person and incurable, terminal disease (cancer) are cumulatively fulfilled. Otherwise it was rejected by most respondents. To a clear majority, active euthanasia implied both the chance that suffering would be shortened, but also the danger of misuse. Among the persons questioned those with professional experience of euthanasia were clearly more sceptical about active euthanasia than those without such experience. CONCLUSIONS: The standardized written questionnaire made it possible to obtain a differentiated picture of public opinion on active euthanasia. However, these data represent only a moment in the dynamic process of a norm being established within a society and must on no account be used as legitimizing active euthanasia by plebiscite.
Assuntos
Atitude Frente a Morte , Eutanásia/psicologia , Opinião Pública , Adulto , Idoso , Idoso de 80 Anos ou mais , Distribuição de Qui-Quadrado , Eutanásia/estatística & dados numéricos , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: Drug resistance represents a complex problem for the treatment of ovarian cancer. This study was undertaken to assess several putative resistance parameters (DRP) in parallel in cancer tissue from newly diagnosed patients with ovarian cancer in order to establish possible correlations to known clinical factors and prognosis. MATERIAL AND METHODS: Tumor and adjacent tumor free ovarian tissue samples from 39 consecutive, untreated female patients with ovarian cancer were obtained and as potential DRPs, the level of glutathione (GSH), the activities of glutathione S-transferase (GST), glutathione-peroxidase (GPx), O6-alkylguanine-DNA alkyltransferase (Atase), and topoisomerase II (TOPO) were assessed biochemically, and P-glycoprotein (Pgp) was assessed by Western blotting. RESULTS: Interindividual variations were high and each patient exhibited an individual profile of resistance factor expression. Levels of GSH were increased with stage (linear trend: P < 0.002), and GST, GPx, and Atase showed a similar tendency. With few exceptions no correlation was found between the DRPs and other prognostic characteristics. All tested DRPs except Pgp showed significantly higher levels/activities in tumor tissues than in the surrounding tumor free tissues (P < 0.05). The tested DRPs were found not to influence response to treatment. CONCLUSIONS: It is concluded that elevated DRPs reflect an intrinsic pattern of components of the detoxifying system in the tumor tissue. This pattern differs between patients and may partly explain the difficulty to assess the clinical importance of individual DRPs in order to translate them into recommendations for specific therapies.
Assuntos
Proteínas de Neoplasias/análise , Neoplasias Ovarianas/química , Adulto , Idoso , DNA Topoisomerases Tipo II/análise , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Feminino , Glutationa/análise , Glutationa Peroxidase/análise , Glutationa Transferase/análise , Humanos , Pessoa de Meia-Idade , O(6)-Metilguanina-DNA Metiltransferase/análise , Neoplasias Ovarianas/tratamento farmacológicoRESUMO
Neither the prevalence of atopic dermatitis (AD) in children nor the magnitude of risk factors such as socioeconomic status or environmental pollution are well known in Germany. In cooperation with the public health service, we therefore carried out a cross-sectional study during a 1992 preschool examination in Hannover covering 4,219 children. Lifetime prevalence of atopic dermatitis was 10.5%; the range for prevalence in 49 districts of Hannover was 2.8-25.0%. The AD prevalence differed significantly between German and non-German children (12.4 vs. 2.1%) and among children from families of different socio-economic status (6.5% low; 18.1% high). Statistically significant associations between AD risk and social variables (family structure, nationality, socio-economic status, occupation) and the lack of definite associations with environmental factors support the hypothesis that life style may be an important risk factor for atopic dermatitis.
Assuntos
Dermatite Atópica/epidemiologia , Neurodermatite/epidemiologia , Fatores Socioeconômicos , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Dermatite Atópica/etiologia , Feminino , Alemanha/epidemiologia , Hierarquia Social , Humanos , Lactente , Masculino , Neurodermatite/etiologia , Fatores de RiscoRESUMO
Drug consumption as an expression of behaviour in good and ill-health shows important aspects of a given population demand behavior in respect of medical goods and services. Therefore, in cooperation with public health services, we carried out a cross-sectional study during 1993 pre-school examinations in the district of Hannover with 4.722 children to investigate their parents' behaviour on drug administration. The aim of this study was to analyse the parents' willingness to give drugs to their children according to specific diseases and disabilities. About 10% of the children were consuming drugs at the time of the investigation. 71% of parents intended to support children with drugs in case of complaints due to illness. More drug consumption was found in single child families, in families with a higher socio-economic status, in families with occupations related to medicine, and in mothers with both occupational and family obligations. The results may be interpreted in terms of a common, socially determined pattern. Parents with special occupational and family obligations tend to be more willing to give their children drugs to react and cope with the situation and their own arodeties.
Assuntos
Tratamento Farmacológico/estatística & dados numéricos , Programas de Rastreamento , Classe Social , Fatores Socioeconômicos , Atitude Frente a Saúde , Criança , Pré-Escolar , Uso de Medicamentos , Feminino , Alemanha/epidemiologia , Humanos , MasculinoRESUMO
BACKGROUND: The identification of new factors predicting relapse, outcome and response to systemic therapy in breast cancer is warranted. The measurement of biological markers such as drug resistance parameters (DRPs), which are part of the phenotype of malignant cells and contribute to resistance to anti-cancer drugs may be a possibility, which may ultimately lead to improvement of therapeutic results. PATIENTS AND METHODS: The level of glutathione (GSH), activities of glutathione-S-transferase (GST), glutathione-peroxidase (GPx), 06-alkylguanine-DNA-alkyltransferase (ATase), and P-glycoprotein (PGP) were measured in tumor and adjacent tumor free tissue samples from 89 consecutive, untreated females with breast cancer and correlated with clinical and prognostic factors. Early breast cancer (EBC) was diagnosed in 56 patients, 22 patients had locally advanced (LABC) and 11 patients metastatic breast cancer. RESULTS: All DRPs showed significantly higher expression in tumor than in tumor free tissues. GPx was positively correlated with GST (r = 0.3, P = 0.0048) and with GSH (r = 0.5, P = 0.0001) in tumor as well as in normal tissue. GST activity was significantly higher in EBC than in LABC or metastatic breast cancer (P = 0.02). GSH level was significantly higher in grade 1 than in grade 2 or grade 3 tumors (P = 0.01). When clinical characteristics were related to the level of DRP, 'high' GSH was associated with age > 60 years (P = 0.01) in EBC, and with grade 1-2 tumors (P = 0.05) in LABC. No differences in OS were apparent between groups of 'high' and 'low' DRP-expression. However, the four-year estimated disease-free survival of EBC tended to be higher in patients with 'high' GST (P = 0.10) and of LABC in patients with 'high' GPx levels (P = 0.06). CONCLUSION: We conclude that 'high' levels of DRP in tumor tissue of breast cancer patients are part of the initial phenotype of the malignant cells. Due to its high prevalence (83% in EBC, 100% in primarily metastatic breast cancer), PGP did not add to prognostic information. High levels of GSH, GST and GPx were associated with favorable clinical characteristics and good prognosis, whereas low levels of GSH and GST activity were associated with more aggressive or more advanced disease.
Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Alquil e Aril Transferases , Neoplasias da Mama/tratamento farmacológico , Glutationa/metabolismo , Transferases/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Resistência a Medicamentos/genética , Feminino , Seguimentos , Glutationa Peroxidase/metabolismo , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Resultado do TratamentoRESUMO
An extended phase II study was performed to evaluate single-agent paclitaxel as salvage chemotherapy for ovarian cancer. The aim of this study was to evaluate the 3-h infusion schedule of paclitaxel in terms of toxicity and antitumour efficacy. Furthermore, we analysed the impact on response and survival of the extent of prior chemotherapy and status of resistance against platinum. This study was an open, non-randomised, multicentre trial. The dose of paclitaxel used was 175 mg/m2 in patients who had received one or two prior therapies, and 135 mg/m2 in patients who had received three prior therapies. Paclitaxel was given as a 3-h infusion. Courses were repeated every 3 weeks. 114 patients with platinum-pretreated epithelial ovarian cancer were recruited of whom 112 were found eligible and evaluable for toxicity. 104 patients with bidimensionally measurable disease who received more than one course of chemotherapy were evaluable for response, progression-free (PFS) and survival. Toxicity was generally manageable. Main toxicities were non-cumulative neutropenia with 22.3% of courses with WHO grade 3/4 and peripheral neuropathy which occurred in more than half of the courses and was of WHO grade 2 and 3 in 20.1 and 1.3% of the courses, respectively. Neuropathy was associated with the higher dose per course and with cumulative paclitaxel dose. Objective responses were reported in 20% (21/104) of the patients (95% CI 13-29%) with a median response duration of 36.7 weeks. Survival and PFS for the whole group were 45.9 and 15.1 weeks, respectively. Performance status, number of tumour lesions and extent of prior chemotherapy were found to be prognostic factors for survival. Extent of prior chemotherapy was the only prognostic factor for PFS. Platinum resistance did not predict response to treatment. Paclitaxel 175 mg/m2 given as a 3-h infusion is an appropriate treatment for patients with platinum-resistant ovarian cancer who have not previously received more than two chemotherapy regimens. Paclitaxel did not show results superior to historical data for platinum retreatment in patients with platinum-sensitive, recurrent ovarian cancer.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Paclitaxel/uso terapêutico , Compostos de Platina/uso terapêutico , Adulto , Idoso , Antineoplásicos Fitogênicos/efeitos adversos , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Infusões Intravenosas , Pessoa de Meia-Idade , Paclitaxel/efeitos adversos , Prognóstico , Fatores de Risco , Terapia de Salvação , Taxa de SobrevidaRESUMO
BACKGROUND: The primary aim was to induce a high number of pCR in early (FIGO IC, IIB + C) - and advanced (FIGO III-IV) - stage ovarian cancer with a surgery plus 4 cycles of cisplatin and melphalan (PAMP) regimen. The second objective was to prevent relapse with WAR in patients in remission after chemotherapy. PATIENTS AND METHODS: 218 eligible patients were treated after staging laparotomy with cisplatin 80 mg/sqm i.v. on day 1 and melphalan 12 mg/sqm i.v. on day 2 q 4 weeks. Response was verified by second-look laparotomy. WAR was carried out with the open field technique on a linear accelerator (daily dose: 1.3 Gy, total dose: 29.9 Gy) in patients with pathological or clinical CR or pathological PR with microscopical residual disease. RESULTS: 146/218 patients (67%, 95% CI: 61%-73%) responded to PAMP: 56 (26%) achieved pCR, 24 (11%), cCR, 56 (26%) pPR and 10 (5%) cPR (c = clinical, p = pathological). Multivariate analyses revealed that in advanced stages (92 cases in remission), the achievement of pCR was the most important factor for longer time to failure (TTF) and survival. Only 51/118 (43%) patients in remission received WAR. Early-stage patients <= 55 years were more likely to have WAR than patients older than 55 years (77% vs. 23%; p = 0.02). Advanced-stage patients with cCR were less likely to be irradiated than patients with pCR or pPR (10% vs. 51%; p = 0.003). Toxicity of PAMP was acceptable with 10% of WHO grade 4 hematologic toxicity. Acute hematological toxicity of WAR caused interruption (33%) or incompleteness (33%) of irradiation in the majority of patients. CONCLUSIONS: PAMP is an effective treatment for advanced ovarian cancer with a 67% response rate after 4 cycles. For the majority of patients in remission, WAR as a consolidation treatment was hardly feasible. For these patients new treatment modalities to consolidate remission are needed.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ovarianas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/administração & dosagem , Terapia Combinada , Esquema de Medicação , Estudos de Viabilidade , Feminino , Humanos , Melfalan/administração & dosagem , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/radioterapia , Neoplasias Ovarianas/cirurgia , Radioterapia/efeitos adversos , Indução de RemissãoRESUMO
P-glycoprotein (Pgp), Glutathione (GSH), Glutathione S-Transferase (GST), and O6-Alkylguanine-DNA Alkyltransferase (ATase) were measured in parallel as putative indicators of drug resistance in adult leukemia. The patterns of resistance parameter expression of chronic and acute leukemia were different. In acute leukemia on average all parameters were increased as compared to normal bone marrow. In chronic leukemia GSH and GST were increased, whereas Atase, GPx and frequency of Pgp-expression were low. Treatment with cytostatic drugs did not influence median levels of expression/activity of the resistance parameters. Resistance parameter expression/activity of leukemic cells was also compared with various other tissue and tumor types. Generally the pattern of resistance parameter expression reflected the resistance status of the tissue, constitutively resistant tumor types and their corresponding normal tissue on average having higher levels than leukemic cells and other tissue and tumor types with acquired resistance. For individual patients with acute leukemia, however, none of the parameters was directly correlated with response to treatment.
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Antineoplásicos/farmacologia , Resistência a Medicamentos/fisiologia , Leucemia Mieloide/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Doença Aguda , Adolescente , Adulto , Idoso , Glutationa/metabolismo , Glutationa Transferase/metabolismo , Humanos , Leucemia Mieloide/enzimologia , Leucemia Mieloide/metabolismo , Metiltransferases/metabolismo , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Neoplasias/enzimologia , Neoplasias/metabolismo , O(6)-Metilguanina-DNA Metiltransferase , Leucemia-Linfoma Linfoblástico de Células Precursoras/enzimologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismoRESUMO
PURPOSE: Taxol (paclitaxel; Bristol-Myers Squibb, Wallingford, CT) is a new anticancer agent with activity in a number of human tumors, including epithelial ovarian cancer. In nonrandomized trials, doses studied have ranged from 135 mg/m2 to 250 mg/m2 administered over 24 hours with premedication to avoid hypersensitivity reactions (HSRs). This study addressed two questions: the dose-response relationship of Taxol in relapsed ovarian cancer and the safety of a short infusion given with premedication. METHODS: Women with platinum-pretreated epithelial ovarian cancer and measurable recurrent disease were randomized in a bifactorial design to receive either 175 or 135 mg/m2 of Taxol over either 24 or 3 hours. Major end points were the frequency of significant HSRs and objective response rate. Secondary end points were progression-free and overall survival. RESULTS: Of 407 patients randomized, 391 were eligible and 382 assessable for response. Analysis was performed according to the bifactorial design. Severe HSRs were rare (1.5% patients) and were not affected by either dose or schedule. Response was slightly higher at the 175-mg/m2 dose (20%) than at 135 mg/m2 (15%), but this was not statistically significant (P = .2). However, progression-free survival was significantly longer in the high-dose group (19 v 14 weeks; P = .02). Significantly more neutropenia was seen when Taxol was administered as a 24-hour infusion. Response rates were similar in the 24- and 3-hour groups (19% and 16%, respectively; P = .6). No survival differences were noted. CONCLUSION: The 3-hour infusion of Taxol is safe when given with premedication and is associated with less neutropenia. There is a modest dose effect with longer time to progression at 175 mg/m2. The observation that longer infusion produces more myelosuppression but does not yield higher response rates should lead to further studies to determine the optimal dose and schedule of this interesting new agent.
Assuntos
Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Paclitaxel/administração & dosagem , Adulto , Idoso , Canadá , Relação Dose-Resposta a Droga , Esquema de Medicação , Europa (Continente) , Feminino , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia/mortalidade , Neoplasias Ovarianas/mortalidade , Paclitaxel/efeitos adversos , Paclitaxel/farmacocinética , Pré-Medicação , Qualidade de Vida , Indução de Remissão , Análise de Sobrevida , Resultado do TratamentoRESUMO
The levels of several potential indicators of drug resistance were measured in tumor and corresponding normal tissue of 55 untreated patients with lung cancer. The resistance parameters include glutathione (GSH) level, activities of the enzymes glutathione transferase (GST), glutathione peroxidase (GPx) and O6-alkylguanine-DNA alkyltransferase (ATase), as well as expression of P-glycoprotein (Pgp). Median values of GSH, GST and GPx were significantly higher in tumor than in normal tissue of non-small-cell lung cancer (NSCLC) or of small-cell lung cancer (SCLC), whereas ATase was elevated in tumor tissue of NSCLC only. Pgp expression as determined by Western blotting was significantly lower in tumor than in normal tissue of NSCLC. Resistance-parameter expression did not correlate with stage of disease or age of the patients. We found a negative correlation between smoking intensity and GSH level in normal tissue. Our findings indicate that the fundamental differences in chemosensitivity between SCLC and NSCLC cannot be explained by differences in the GSH-system or in the expression of Pgp. However, the level of ATase activity may be one of the factors responsible for the difference in chemosensitivity.
Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Resistência a Medicamentos , Glutationa/metabolismo , Neoplasias Pulmonares/metabolismo , Pulmão/metabolismo , Metiltransferases/metabolismo , Adenocarcinoma/metabolismo , Adulto , Idoso , Western Blotting , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma de Células Pequenas/metabolismo , Carcinoma de Células Escamosas/metabolismo , Feminino , Glutationa Peroxidase/metabolismo , Glutationa Transferase/metabolismo , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , O(6)-Metilguanina-DNA Metiltransferase , Fumar/metabolismoRESUMO
BACKGROUND: This prospective, randomized, double-blind study assessed whether the addition of dexamethasone to ondansetron leads to improved control of chemotherapy--induced emesis, both in patients undergoing their first course of highly emetogenic chemotherapy and in chemotherapy-pretreated patients refractory to standard anti-emetics. PATIENTS AND METHODS: Patients were randomized to receive either 20 mg dexamethasone as an intravenous infusion or placebo plus ondansetron 8 mg 15 minutes prior to and 4 and 8 hours after the administration of chemotherapy. According to the randomisation code patients received from day 2 to day 5 either ondansetron 8 mg p.o. + placebo p.o., three times daily, or ondansetron 8 mg p.o. + dexamethasone 4 mg p.o., three times daily. Patients undergoing multiple-day treatment received intravenous study treatment on the days of chemotherapy and thereafter oral treatment as outlined above. RESULTS: A total of 215 patients were entered into the study. Of these, 207 were evaluable (111 previously-untreated and 96 previously-treated patients). In the chemotherapy-naive patients the combination of ondansetron plus dexamethasone was significantly superior to ondansetron plus placebo in protecting the patients completely from emesis (retching and vomiting) (81% versus 64%, p = 0.04). The mean number of vomiting episodes was significantly lower in the ondansetron-plus-dexamethasone-treated patients than in those receiving ondansetron plus placebo (0.8 versus 2.1, p = 0.03). In this group of patients there was significantly superior protection from emesis on the second day (p-value = 0.04), and a trend towards a better protection on the third and fourth days. On each day the active combination offered better protection from nausea with an approximately 20% difference in favor of ondansetron plus dexamethasone. In the group of established vomiters the combination of ondansetron plus dexamethansone was superior to ondansetron plus placebo in protecting the patients from acute emesis, with 70% versus 48% of the patients being completely protected (p = 0.03). The mean number of vomiting episodes was significantly lower in the ondansetron-plus-dexamethasone-treated-patients than in those receiving ondansetron plus placebo (0.9 versus 2.1, p = 0.02). In the ondansetron-plus-dexamethasone arm 55% of the patients had complete protection from nausea, retching and vomiting compared to 35% in the ondansetron-plus-placebo-treated group (p = 0.05). Overall 22% of the patients (20% in the ondansetron-plus-placebo and 25% in the ondansetron-plus-dexamethasone arm) experienced at least one, usually mild, adverse event. More patients in the ondansetron-plus-dexamethasone arm complained of epigastric pain or burning (8/101 versus 4/112, p-value = 0.16). The difference in patients reporting constipation (6/101 versus 0/112) was highly significant at a p-value of 0.008. CONCLUSIONS: The combination of dexamethasone plus ondansetron is more effective in protecting chemotherapy-naive patients undergoing their first course of highly emetogenic chemotherapy with cisplatin and chemotherapy-pretreated patients refractory to standard antiemetics from chemotherapy-induced nausea and vomiting compared to ondansetron plus placebo.