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1.
Lung Cancer ; 146: 217-223, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32569900

RESUMO

BACKGROUND: Cancer cases among the population of the canton Zurich, are registered in the Cancer Registry of the cantons of Zurich and Zug (KKR). The Thoracic Oncology Center, founded in 2011 is one of 17 multidisciplinary centers within the Comprehensive Cancer Center Zurich (CCCZ). METHODS: The aim of the current study is to quantify the mortality risk of patients with NSCLC and identify differences on survival and other factors between patients receiving their primary treatment at the CCCZ and those treated elsewhere and registered by KKR. The differential effect between CCCZ and KKR cohorts on survival: overall, by stage, sex and age, is explored. Stratified log-rank and Wilcoxon tests, Cox models and restricted mean survival times (RMST) are estimated. Propensity score matching (PSM) is also used to adjust for confounding factors. RESULTS: Analysis included 848 NSCLC cases from the CCCZ and 1759 from the KKR, diagnosed between January 2011 and December 2015. At a median follow-up of 57 months, overall survival (OS) was significantly superior for patients treated at the CCCZ compared to KKR [Median OS: 36.0 months (95%CI: 31.0-45.0) and 12.0 months (95%CI: 11.0-13.0), respectively, stratified log-rank p < 0.001; adjusted HR = 1.31, (95% CI: 1.18-1.46), difference in RMST up to 72 months: 13.8 months (95%CI: 11.5-16.2), p < 0.001]. The effect of cohort was significant for stages III and IV (overall and also by sex and age). After PSM OS remained significantly superior for patients treated at the CCCZ compared to KKR. CONCLUSIONS: The survival probability for patients in the CCCZ cohort was superior to that of patients in the canton Zürich treated outside the center. This analysis provides further evidence of the importance of the volume of experience and the availability of a multidisciplinary organization and research environment, as delivered by a comprehensive cancer center, on the outcome of patients with NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Pontuação de Propensão , Modelos de Riscos Proporcionais , Sistema de Registros
2.
Bone Marrow Transplant ; 41(6): 547-54, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18026149

RESUMO

The role of high-dose chemotherapy (HDCT) in epithelial ovarian cancer (EOC) remains controversial. This study was initiated to compare the efficacy and tolerability of HDCT as a consolidation approach in women with chemosensitive advanced EOC (FIGO stages IIC-IV). Patients who had achieved their first clinical complete remission after six cycles of conventional paclitaxel and carboplatin combination chemotherapy were randomly assigned to receive or not high-dose melphalan. The primary objective was to compare time to disease progression (TTP). A total of 80 patients were enrolled onto the trial. Patients who were randomized to receive HDCT were initially treated with cyclophosphamide 4 g/m(2) for PBPC mobilization. HDCT consisted of melphalan 200 mg/m(2). Of the 37 patients who were allocated to HDCT, 11 (29.7%) did not receive melphalan either due to patient refusal (n=5) or due to failure of PBPC mobilization (n=6). In an intent-to-treat analysis, there were no significant differences between the two arms in TTP (P=0.059) as well as in overall survival (OS) (P=0.38).


Assuntos
Antineoplásicos Alquilantes/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Melfalan/administração & dosagem , Neoplasias Ovarianas/terapia , Adjuvantes Imunológicos/administração & dosagem , Adulto , Idoso , Antineoplásicos Alquilantes/efeitos adversos , Transfusão de Sangue Autóloga , Terapia Combinada , Ciclofosfamida/administração & dosagem , Progressão da Doença , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Humanos , Lenograstim , Melfalan/efeitos adversos , Pessoa de Meia-Idade , Neoplasias Ovarianas/mortalidade , Proteínas Recombinantes/administração & dosagem , Análise de Sobrevida , Fatores de Tempo
3.
Ann Oncol ; 19(5): 853-60, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18042835

RESUMO

BACKGROUND: A randomized phase III trial in high-risk breast cancer patients was conducted, to further explore the impact of dose-density in the adjuvant treatment for breast cancer. The safety analysis is presented. PATIENTS AND METHODS: From October 2000 until June 2005, 1121 node-positive patients were randomized to sequential dose-dense epirubicin 110 mg/m(2) and paclitaxel (Taxol, Bristol Myers-Squibb, Princeton, New Jersey, USA) 250 mg/m(2) (group A), or concurrent epirubicin 83 mg/m(2) and paclitaxel 187 mg/m(2) (group B), both followed by three cycles of 'intensified' combination chemotherapy with cyclophosphamide, methotrexate and fluorouracil (CMF). Granulocyte colony-stimulating factor was given prophylactically with the dose-dense treatments. RESULTS: Median dose intensity of epirubicin and paclitaxel was double in group A, as designed, with significantly less cycles administered at full dose (P < 0.001). Median cumulative dose of all drugs and total treatment duration, however, were identical between groups. Severe taxane-related toxic effects were more frequent in group A, while severe thrombocytopenia was low and present only in group A. There were no differences in the rates of other hematological toxic effects, including febrile neutropenia. The rates of secondary malignancies were low. CONCLUSION: Both regimens as used in the present study are well tolerated and safe. The rates of severe taxane-related toxic effects and thrombocytopenia, although low overall, are significantly increased with the dose-dense sequential regimen.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carcinoma/tratamento farmacológico , Quimioterapia Adjuvante , Mastectomia , Adulto , Idoso , Androstadienos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Carcinoma/radioterapia , Carcinoma/secundário , Carcinoma/cirurgia , Terapia Combinada , Ciclofosfamida/administração & dosagem , Relação Dose-Resposta a Droga , Epirubicina/administração & dosagem , Estrogênios , Feminino , Fluoruracila/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Doenças Hematológicas/induzido quimicamente , Humanos , Metástase Linfática , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Neoplasias Hormônio-Dependentes/cirurgia , Segunda Neoplasia Primária/epidemiologia , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Tamoxifeno/administração & dosagem
4.
Ann Oncol ; 17(10): 1504-11, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16968874

RESUMO

PURPOSE: To assess the prognostic and predictive significance of p53 and Bcl-2 protein expression in high risk patients with breast cancer treated with dose-dense sequential chemotherapy. PATIENTS AND METHODS: From June 1997 until November 2000, 595 patients were randomized to three cycles of epirubicin (E) 110 mg/m2 followed by three cycles of paclitaxel (P) 250 mg/m2 followed by three cycles of 'intensified' CMF (cyclophosphamide 840 mg/m2, methotrexate 47 mg/m2 and fluorouracil 840 mg/m2) or to four cycles of E, followed by four cycles of CMF. p53 and Bcl-2 expression was investigated by immunohistochemistry in 392 and 397 patients respectively. RESULTS: Positive expression of p53 was detected in 104 (26.5%) patients and was significantly associated with negative hormonal status, worse histologic grade, higher incidence of disease relapse and higher rate of death. p53 positive expression was a significant negative predictor of overall survival (OS) (P = 0.002) and disease-free survival (DFS) (P = 0.001). Negative expression of Bcl-2 was detected in 203 (51%) patients and was significantly associated with negative hormonal status. Multivariate analysis revealed that, positive p53 expression, higher number of positive nodes and worse tumor grade were related to significantly poorer OS and DFS. CONCLUSIONS: For both treatments, p53 positive expression was a significant negative prognostic factor for OS and DFS while Bcl-2 was not. No predictive ability of p53 status or Bcl-2 status for paclitaxel treatment was evident.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/diagnóstico , Carcinoma Ductal de Mama/diagnóstico , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/mortalidade , Carcinoma Ductal de Mama/patologia , Quimioterapia Adjuvante , Ciclofosfamida/administração & dosagem , Relação Dose-Resposta a Droga , Epirubicina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Expressão Gênica , Humanos , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Técnicas de Diagnóstico Molecular/métodos , Paclitaxel/administração & dosagem , Valor Preditivo dos Testes , Prognóstico , Análise de Sobrevida
5.
Ann Oncol ; 16(11): 1762-71, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16148021

RESUMO

PURPOSE: The aim of this study was to explore the effect of dose-dense sequential chemotherapy with or without paclitaxel primarily on disease-free survival (DFS) and secondarily on overall survival (OS) in patients with high-risk operable breast cancer. PATIENTS AND METHODS: From June 1997 until November 2000, 604 patients with T1-3N1M0 or T3N0M0 tumors were randomized to three cycles of epirubicin 110 mg/m2 followed by three cycles of paclitaxel 250 mg/m2 followed by three cycles of 'intensified' CMF (cyclophosphamide 840 mg/m2, methotrexate 47 mg/m2 and fluorouracil 840 mg/m2) (group A), or to four cycles of epirubicin followed by four cycles of CMF, as in group A (group B). All cycles were given every 2 weeks with granulocyte colony-stimulating factor support. RESULTS: A total of 595 patients were eligible. Median follow-up was 61.7 months for group A and 62 months for group B. The 3-year DFS was 80% in group A and 77% in group B. Survival rates were 93% and 90%, respectively. The effect of treatment on the hazard of death was different according to hormonal receptor status. More specifically, in patients with negative receptor status the hazard of death was significantly higher for group B (hazard ratio 2.42). Both regimens were well tolerated and severe acute side-effects were infrequent. No cases of severe cardiotoxicity or acute leukemia were recorded. CONCLUSIONS: The present study failed to demonstrate a significant difference in DFS or OS between the two treatment groups. However, our study has shown clearly that high-dose paclitaxel can be safely incorporated to dose-dense sequential chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/cirurgia , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Epirubicina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Fatores de Risco , Taxa de Sobrevida , Resultado do Tratamento
6.
Oncology ; 58(3): 227-36, 2000 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10765125

RESUMO

BACKGROUND: It has been shown in randomized studies that adjuvant treatment with the combination of fluorouracil (FU) and levamisole reduced the risk of recurrence and deaths of patients with stage III colon cancer. Pharmacological studies of FU led to its use in combination with a number of modulating agents including interferon-alpha and leucovorin (LV) that appear to enhance its activity in vitro. Furthermore, a meta-analysis suggested that the combination of FU with LV increased the response rate as compared to FU monotherapy in patients with advanced colorectal cancer. PURPOSE: To evaluate the impact of adjuvant treatment with the combination of FU and LV with or without interferon alfa-2a (IFN) on disease-free survival (DFS) and overall survival (OS) for patients with stage II or III colon cancer. PATIENTS AND METHODS: From August 1989 to July 1997, 280 patients with stage II and III colon cancer entered the study and were randomly assigned to receive either the combination of FU (600 mg/m(2)/week x 6, followed by a 2-week rest) and LV (500 mg/m(2)/week x 6 as a 2-hour infusion, followed by a 2-week rest) for 4 cycles (group A, 139 patients), or the same chemotherapy plus recombinant IFN (3 MU subcutaneously 3 times a week) for 1 year (group B, 141 patients). RESULTS: A total of 109 patients (78.9%) of group A and 119 (84.4%) of group B completed four cycles of chemotherapy. Also, 51.4% of patients of group A and 53.9% of group B received > or =80% of the planned dose of FU. One patient (group A) was found to be ineligible and was not included in the analysis. The median relative dose intensity of FU in the two groups was 0.90 and 0.85, respectively. As of August 1998, after a median follow up of 4 years, there was no significant difference in either 3-year DFS (group A, 83.1%; group B, 75.9%, p = 0.14) or OS (group A, 84.5%; group B, 80.0%, p = 0.27). In the Cox model, stage of disease, number of infiltrated nodes, tumor grade and presence of regional implants were identified as significant prognostic factors for OS. Grade 3-4 toxicities, mainly diarrhea, were observed in 26.1% of patients of group A and in 24.8% of group B. There were no treatment-related deaths. CONCLUSIONS: The addition of IFN to the combination of FU with LV postoperatively does not improve DFS and OS of patients with stage II or III colon cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Interferon-alfa/uso terapêutico , Adulto , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias do Colo/patologia , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Humanos , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Interferon-alfa/efeitos adversos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Proteínas Recombinantes , Análise de Sobrevida , Resultado do Tratamento
7.
Ann Oncol ; 10(6): 671-6, 1999 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10442189

RESUMO

BACKGROUND: Randomized studies have shown that postoperative chemotherapy with or without radiation therapy (RT) improved local control and survival of patients with stages II or III rectal cancer. However, the optimal sequence of treatments and the optimal chemotherapeutic regimen have not been defined. Modulation of fluorouracil (FU) by leucovorin (LV) has yielded a highly significant difference in response rate from that of FU monotherapy, as suggested by an overview of randomized trials in patients with advanced colorectal cancer. However, this difference in response rate did not translate into a survival benefit. PURPOSE: To evaluate the impact on the disease-free survival (DFS) and overall survival (OS) of patients with stages II or III rectal cancer of postoperative RT and concomitant bolus FU administration alone or with additional chemotherapy using FU and high-dose LV. PATIENTS AND METHODS: From October 1989 until February 1997, 220 patients were randomized postoperatively to receive either one cycle of chemotherapy with FU (600 mg/m2/week x 6 followed by a two-week rest) and leucovorin (LV, 500 mg/m2/week x 6 as a two-hour infusion) followed by pelvic RT with concomitant FU (400 mg/m2) as a rapid intravenous injection during the first three and last three days of RT, and three more cycles of the same chemotherapy with FU and LV (standard, group A, 111 patients) or pelvic RT with concomitant FU only (experimental, group B, 109 patients). RESULTS: As of August 1998, after a median follow-up of 4.9 years, there was no significant difference in either three-year DFS (Group A, 70.3%; group B, 68.2%, P = 0.53) or OS (group A, 77%; group B, 73.3%. P = 0.75). Cox multivariate analysis revealed stage of disease, number of infiltrated nodes, tumor grade, presence of regional implants and perforation to be significant prognostic factors. The incidence of severe side effects was significantly higher in the patients in group A than in those in group B (32.4% vs. 4.6%, P < 0.0001). CONCLUSIONS: The incorporation of additional chemotherapy with FU and LV into postoperative concomitant RT and bolus infusion of FU does not offer a > or = 10% three-year survival benefit over that of concomitant RT and bolus infusion of FU, and significantly increases toxicity in patients with stages II or III rectal cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Retais/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Terapia Combinada , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Humanos , Injeções Intravenosas , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Neoplasias Retais/patologia , Neoplasias Retais/radioterapia , Análise de Sobrevida , Resultado do Tratamento
8.
Neurology ; 51(1): 221-8, 1998 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9674806

RESUMO

BACKGROUND: Few effective treatments are available for AIDS dementia complex (ADC) and HIV-associated neuropathy. However, recent in vitro studies indicate that nimodipine, a voltage-dependent calcium channel antagonist, can prevent HIV-related neuronal injury and may provide a novel form of treatment for these disorders. METHODS: To determine the safety and possible efficacy of this agent, 41 patients with mild to severe ADC, including 19 patients with neuropathy, were entered into the AIDS Clinical Trial Group multicenter, phase-I and phase-II study. Nimodipine at 60 mg p.o., five times daily; 30 mg p.o., three times daily; or placebo was administered for 16 weeks as adjuvant treatment to antiretroviral therapy. RESULTS: Neuropsychological performance at baseline, measured by the composite neuropsychological Z score (NPZ-8), correlated significantly with the ADC stage and with CSF levels of neopterin, a marker of immune activation. No significant differences in toxicity were observed among the three arms. Intent-to-treat analysis showed no significant change in the NPZ-8, although improvement was suggested in the high-dose arm. In addition, a trend toward stabilization in peripheral neuropathy was observed in both nimodipine arms compared with placebo. CONCLUSIONS: Nimodipine and other similar nonantiretroviral agents may provide a safe and promising avenue of treatment for neurologic disorders associated with HIV infection. The results of this study indicate that further clinical trials are warranted.


Assuntos
Complexo AIDS Demência/tratamento farmacológico , Bloqueadores dos Canais de Cálcio/administração & dosagem , Neurite (Inflamação)/virologia , Nimodipina/administração & dosagem , Adulto , Fármacos Anti-HIV/administração & dosagem , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neurite (Inflamação)/tratamento farmacológico , Testes Neuropsicológicos , Desempenho Psicomotor , Zidovudina/administração & dosagem
9.
Chest ; 113(1): 8-14, 1998 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9440560

RESUMO

BACKGROUND AND STUDY OBJECTIVE: Phrenic nerve injury may occur after cardiac surgery; however, its cause has not been extensively investigated with electrophysiology. The purpose of this study was to determine by electrophysiologic means the importance of various possible risk factors in the development of phrenic nerve dysfunction after cardiac surgical operations. DESIGN: A prospective study was conducted. SETTING: A tertiary teaching hospital provided the background for the study. PATIENTS: Sixty-three cardiac surgery patients on whom surgical operations were performed by the same surgical team constituted the study group. Mean (+/-SD) age and ejection fraction were 63+/-5 years and 50+/-10%, respectively. INTERVENTIONS: Measurement of phrenic nerve conduction latency time after transcutaneous stimulation preoperatively and at 24 h and 7 and 30 days postoperatively. RESULTS: Thirteen patients had abnormal phrenic nerve function postsurgery, 12 on the left side and one bilaterally. Logistic regression analysis revealed that among the potential risk factors investigated, use of ice slush for myocardial preservation was the only independent risk factor related to phrenic nerve dysfunction (p=0.01), carrying an 8-fold higher incidence for this complication. In contrast, age, ejection fraction of the left ventricle, operative/bypass/aortic cross-clamp time, left internal mammary artery use, and diabetes mellitus were not found to be associated with phrenic neuropathy. The postoperative outcome of patients who received ice slush compared with that of those who had cold saline solution did not differ in terms of early morbidity and mortality. CONCLUSION: Among the risk factors investigated, only the use of ice slush was significantly associated with postoperative phrenic nerve dysfunction. Therefore, ice should be avoided in cardiac surgery, since it does not seem to provide additional myocardial protection.


Assuntos
Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Nervo Frênico/patologia , Complicações Pós-Operatórias , Idoso , Condutividade Elétrica , Eletrofisiologia/métodos , Feminino , Seguimentos , Parada Cardíaca Induzida/efeitos adversos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/cirurgia , Condução Nervosa/fisiologia , Doenças do Sistema Nervoso Periférico/diagnóstico , Doenças do Sistema Nervoso Periférico/etiologia , Doenças do Sistema Nervoso Periférico/fisiopatologia , Nervo Frênico/fisiopatologia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/fisiopatologia , Estudos Prospectivos , Radiografia Torácica , Fatores de Risco , Estimulação Elétrica Nervosa Transcutânea
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