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1.
Breast Cancer Res Treat ; 158(3): 485-95, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27393622

RESUMO

SWOG S0800, a randomized open-label Phase II clinical trial, compared the combination of weekly nab-paclitaxel and bevacizumab followed by dose-dense doxorubicin and cyclophosphamide (AC) with nab-paclitaxel followed or preceded by AC as neoadjuvant treatment for HER2-negative locally advanced breast cancer (LABC) or inflammatory breast cancer (IBC). Patients were randomly allocated (2:1:1) to three neoadjuvant chemotherapy arms: (1) nab-paclitaxel with concurrent bevacizumab followed by AC; (2) nab-paclitaxel followed by AC; or (3) AC followed by nab-paclitaxel. The primary endpoint was pathologic complete response (pCR) with stratification by disease type (non-IBC LABC vs. IBC) and hormone receptor status (positive vs. negative). Overall survival (OS), event-free survival (EFS), and toxicity were secondary endpoints. Analyses were intent-to-treat comparing bevacizumab to the combined control arms. A total of 215 patients were accrued including 11 % with IBC and 32 % with triple-negative breast cancer (TNBC). The addition of bevacizumab significantly increased the pCR rate overall (36 vs. 21 %; p = 0.019) and in TNBC (59 vs. 29 %; p = 0.014), but not in hormone receptor-positive disease (24 vs. 18 %; p = 0.41). Sequence of administration of nab-paclitaxel and AC did not affect the pCR rate. While no significant differences in OS or EFS were seen, a trend favored the addition of bevacizumab for EFS (p = 0.06) in TNBC. Overall, Grade 3-4 adverse events did not differ substantially by treatment arm. The addition of bevacizumab to nab-paclitaxel prior to dose-dense AC neoadjuvant chemotherapy significantly improved the pCR rate compared to chemotherapy alone in patients with triple-negative LABC/IBC and was accompanied by a trend for improved EFS. This suggests reconsideration of the role of bevacizumab in high-risk triple-negative locally advanced breast cancer.


Assuntos
Albuminas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bevacizumab/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Paclitaxel/administração & dosagem , Adulto , Idoso , Albuminas/uso terapêutico , Bevacizumab/uso terapêutico , Ciclofosfamida/uso terapêutico , Intervalo Livre de Doença , Doxorrubicina/uso terapêutico , Esquema de Medicação , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Paclitaxel/uso terapêutico , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
2.
Pharmacogenomics J ; 14(3): 241-7, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23999597

RESUMO

Hematological and gastrointestinal toxicities are common among patients treated with cyclophosphamide and doxorubicin for breast cancer. To examine whether single-nucleotide polymorphisms (SNPs) in key pharmacokinetic genes were associated with risk of hematological or gastrointestinal toxicity, we analyzed 78 SNPs in ABCB1, ABCC1 and ALDH1A1 in 882 breast cancer patients enrolled in the SWOG trial S0221 and treated with cyclophosphamide and doxorubicin. A two-SNP haplotype in ALDH1A1 was associated with an increased risk of grade 3 and 4 hematological toxicity (odds ratio=1.44, 95% confidence interval=1.16-1.78), which remained significant after correction for multiple comparisons. In addition, four SNPs in ABCC1 were associated with gastrointestinal toxicity. Our findings provide evidence that SNPs in pharmacokinetic genes may have an impact on the development of chemotherapy-related toxicities. This is a necessary first step toward building a clinical tool that will help assess risk of adverse outcomes before undergoing chemotherapy.


Assuntos
Aldeído Desidrogenase/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Família Aldeído Desidrogenase 1 , Neoplasias da Mama/genética , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Humanos , Polimorfismo de Nucleotídeo Único , Retinal Desidrogenase
3.
Ann Oncol ; 24(2): 355-361, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23028039

RESUMO

BACKGROUND: MA17 showed improved outcomes in postmenopausal women given extended letrozole (LET) after completing 5 years of adjuvant tamoxifen. PATIENTS AND METHODS: Exploratory subgroup analyses of disease-free survival (DFS), distant DFS (DDFS), overall survival (OS), toxic effects and quality of life (QOL) in MA17 were performed based on menopausal status at breast cancer diagnosis. RESULTS: At diagnosis, 877 women were premenopausal and 4289 were postmenopausal. Extended LET was significantly better than placebo (PLAC) in DFS for premenopausal [hazard ratio (HR) = 0.26, 95% confidence interval (CI) 0.13-0.55; P = 0.0003] and postmenopausal women (HR = 0.67; 95% CI 0.51-0.89; P = 0.006), with greater DFS benefit in those premenopausal (interaction P = 0.03). In adjusted post-unblinding analysis, those who switched from PLAC to LET improved DDFS in premenopausal (HR = 0.15; 95% CI 0.03-0.79; P = 0.02) and postmenopausal women (HR = 0.45; 95% CI 0.22-0.94; P = 0.03). CONCLUSIONS: Extended LET after 5 years of tamoxifen was effective in pre- and postmenopausal women at diagnosis, and significantly better in those premenopausal. Women premenopausal at diagnosis should be considered for extended adjuvant therapy with LET if menopausal after completing tamoxifen.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Nitrilas/uso terapêutico , Pré-Menopausa , Triazóis/uso terapêutico , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Inibidores da Aromatase/efeitos adversos , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/diagnóstico , Quimioterapia Adjuvante , Intervalo Livre de Doença , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Letrozol , Pessoa de Meia-Idade , Nitrilas/efeitos adversos , Placebos , Pós-Menopausa , Qualidade de Vida , Sobrevida , Tamoxifeno/uso terapêutico , Resultado do Tratamento , Triazóis/efeitos adversos
4.
Ann Oncol ; 19(5): 877-82, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18332043

RESUMO

BACKGROUND: MA.17 evaluated letrozole or placebo after 5 years of tamoxifen and showed significant improvement in disease-free survival (DFS) for letrozole [hazard ratio (HR) 0.57, P = 0.00008]. The trial was unblinded and placebo patients were offered letrozole. PATIENTS AND METHODS: An intent-to-treat analysis of all outcomes, before and after unblinding, on the basis of the original randomization was carried out. RESULTS: In all, 5187 patients were randomly allocated to the study at baseline and, at unblinding, 1579 (66%) of 2383 placebo patients accepted letrozole. At median follow-up of 64 months (range 16-95), 399 recurrences or contralateral breast cancers (CLBCs) (164 letrozole and 235 placebo) occurred. Four-year DFS was 94.3% (letrozole) and 91.4% (placebo) [HR 0.68, 95% confidence interval (CI) 0.55-0.83, P = 0.0001] and showed superiority for letrozole in both node-positive and -negative patients. Corresponding 4-year distant DFS was 96.3% and 94.9% (HR 0.80, 95% CI 0.62-1.03, P = 0.082). Four-year overall survival was 95.1% for both groups. The annual rate of CLBC was 0.28% for letrozole and 0.46% for placebo patients (HR 0.61, 95% CI 0.39-0.97, P = 0.033). CONCLUSIONS: Patients originally randomly assigned to receive letrozole within 3 months of stopping tamoxifen did better than placebo patients in DFS and CLBC, despite 66% of placebo patients taking letrozole after unblinding.


Assuntos
Antineoplásicos/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , Estrogênios , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Nitrilas/uso terapêutico , Progesterona , Triazóis/uso terapêutico , Antineoplásicos/administração & dosagem , Antineoplásicos Hormonais/uso terapêutico , Inibidores da Aromatase/administração & dosagem , Intervalo Livre de Doença , Método Duplo-Cego , Humanos , Estimativa de Kaplan-Meier , Letrozol , Metástase Linfática , Segunda Neoplasia Primária/tratamento farmacológico , Segunda Neoplasia Primária/epidemiologia , Nitrilas/administração & dosagem , Aceitação pelo Paciente de Cuidados de Saúde , Placebos , Pós-Menopausa , Modelos de Riscos Proporcionais , Recidiva , Tamoxifeno/uso terapêutico , Triazóis/administração & dosagem
5.
Ann Oncol ; 16(7): 1076-80, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15860488

RESUMO

BACKGROUND: There are no published prospective trials of chemotherapy for advanced bronchioloalveolar carcinoma (BAC), a subtype of non-small-cell lung cancer for which there is no current standard therapy. This phase II study assesses the efficacy and toxicity of 96-h paclitaxel in chemotherapy-naive patients with advanced BAC. PATIENTS AND METHODS: Patients with histologically confirmed stage IIIB (with pleural effusion) or stage IV BAC were eligible. Treatment consisted of paclitaxel 35 mg/m2/24 h continuously infused over 96 h (days 1-4) every 21 days for up to six courses. RESULTS: A total of 58 eligible patients were enrolled. The objective response rate was 14% (all partial responses, 9% confirmed); 40% of patients demonstrated stable disease. The median progression-free and overall survivals were 5 and 12 months, respectively. Grade 3 or greater toxicities included neutropenia/granulocytopenia (43%), febrile neutropenia (12%), infection (22%), and stomatitis/pharyngitis (10%); there were five treatment-related deaths. CONCLUSIONS: S9714 represents the first prospective multi-institutional cooperative group trial focusing on treatment outcomes in BAC. Studies targeting this population are feasible, and while first-line paclitaxel administered as a prolonged infusion is active in this setting, toxicities limits the utility of this regimen. S9714 serves as a historical control for BAC patients against which future therapeutic approaches can be compared.


Assuntos
Adenocarcinoma Bronquioloalveolar/tratamento farmacológico , Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Paclitaxel/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/efeitos adversos , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Análise de Sobrevida
6.
Lung Cancer ; 37(3): 303-9, 2002 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12234700

RESUMO

This study evaluates the influence of gender on survival and tumor recurrence following adjuvant therapy of completely resected stages II and IIIa non-small cell lung cancer (NSCLC). The Eastern Cooperative Oncology Group conducted a randomized prospective trial of adjuvant therapy in patients with completely resected stages II and IIIa NSCLC. A laboratory correlative study assessed the prevalence and prognostic significance of p53 and K-ras mutations. Patients were randomized to receive either radiotherapy (RT) alone or four cycles of cisplatin and VP-16 administered concurrently with radiotherapy (CRT). Median survival was 35 months for the 285 men and 41 months for the 203 women enrolled in the study (P = 0.12). The relative risk (RR) of death for men vs women was 1.19 (95% confidence interval [CI], 0.95-1.49). Median survival of the 147 men and 95 women randomized to the RT arm was 39 months each (P = 0.35). Median survival of the 138 men and 108 women randomized to the CRT arm was 30 and 42 months, respectively (P = 0.18). Disease recurrence patterns were similar between the genders. Univariate and multivariate analyses demonstrated improved survival for women with tumors of non-squamous histology (P < 0.01). The distribution of p53 and K-ras mutations was similar between the genders and had no influence on survival. Gender does not influence survival following adjuvant RT or CRT administered to patients with completely resected stages II and IIIa NSCLC. However, women with non-squamous histology have increased survival when compared to men.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares , Recidiva Local de Neoplasia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Radioterapia Adjuvante , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores Sexuais , Sobrevida
7.
Percept Mot Skills ; 93(1): 78-80, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11693710

RESUMO

The construct validity of the Verbal Comprehension. Perceptual Organization, and Freedom from Distractibility factor scores was examined in a sample of school-aged referred children. Examination of correlations between factor scores and neuropsychological and achievement tests generally supported the construct validity of the factors. The Verbal Comprehension factor was associated with verbal, quantitative, and concept-formation abilities. The Perceptual Organization factor was related to nonverbal concept formation, tactual performance, and visual attention. The Freedom from Distractibility factor demonstrated a complex pattern of correlations and appeared to reflect a range of abilities including quantitative, language, attentional, and concept formation.


Assuntos
Escalas de Wechsler , Adolescente , Criança , Cognição/fisiologia , Formação de Conceito/fisiologia , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes
9.
Lung Cancer ; 33(2-3): 213-9, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11551416

RESUMO

PURPOSE: To report the long-term follow-up of Southwest Oncology Group-8269, a phase II North American cooperative group trial of concurrent cisplatin, etoposide, vincristine (PEV), and thoracic radiotherapy (TRT) for limited small-cell lung cancer (L-SCLC). METHODS: 114 eligible patients from 47 institutions enrolled between April, 1985 and March 1986. Patients had documented L-SCLC. Induction chemotherapy consisted of three cycles of PEV. TRT was administered at 1.8 Gy/fraction in 25 daily fractions to a total dose of 45 Gy, to begin concomitantly. Consolidative chemotherapy included two cycles of vincristine, methotrexate, etoposide, doxorubicin and cyclophosphamide. Prophylactic cranial irradiation (PCI) was concurrent with the 3rd cycle of chemotherapy. The PCI dose was 30 Gy in 15 fractions of 2 Gy/fraction. RESULTS: As of May 2000, 5 of 114 remain alive and progression-free with a minimum follow-up interval of 13.2 years, as of May 2000. The median follow-up interval is 14.2 years. Thirty eight patients died of causes other than SCLC and five patients are still alive and progression-free. Of the remaining 71 patients dying of SCLC, local failure (LF) occurred in 24% (17 patients), distant metastasis (DM) occurred in 35% (25 patients), simultaneous LF and DM occurred in 25% (18 patients), and was indeterminate in 16% (11 patients). Thus, LF was a component of failure in 49%. Twenty patients had the CNS as the initial site of failure. Eleven patients (10%) developed fatal second primary cancers, including two with acute myelogenous leukemia, two with squamous cell lung cancer, one each with breast, pancreas, prostate, renal cell, and myelodysplasia. One patient developed both a melanoma and non-Hodgkin's lymphoma. CONCLUSION: There are long-term survivors with concomitant TRT and PEV. LF and DM are common. Pattern of failure suggests needs to improve local and systemic control.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Pequenas/tratamento farmacológico , Carcinoma de Células Pequenas/radioterapia , Cisplatino/uso terapêutico , Etoposídeo/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Vimblastina/uso terapêutico , Carcinoma de Células Pequenas/mortalidade , Estudos de Coortes , Intervalo Livre de Doença , Seguimentos , Humanos , Neoplasias Pulmonares/mortalidade , Estadiamento de Neoplasias , Taxa de Sobrevida
10.
J Clin Oncol ; 19(15): 3516-23, 2001 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-11481358

RESUMO

PURPOSE: To determine the prevalence of suspected disease in the mediastinum and internal mammary (IM) node chain by 18fluorodeoxyglucose (FDG) positron emission tomography (PET), compared with conventional staging by computed tomography (CT) in patients with recurrent or metastatic breast cancer. PATIENTS AND METHODS: We retrospectively evaluated intrathoracic lymph nodes using FDG PET and CT data in 73 consecutive patients with recurrent or metastatic breast cancer who had both CT and FDG PET within 30 days of each other. In reviews of CT scans, mediastinal nodes measuring 1 cm or greater in the short axis were considered positive. PET was considered positive when there were one or more mediastinal foci of FDG uptake greater than the mediastinal blood pool. RESULTS: Overall, 40% of patients had abnormal mediastinal or IM FDG uptake consistent with metastases, compared with 23% of patients who had suspiciously enlarged mediastinal or IM nodes by CT. Both FDG PET and CT were positive in 22%. In the subset of 33 patients with assessable follow-up by CT or biopsy, the sensitivity, specificity, and accuracy for nodal disease was 85%, 90%, and 88%, respectively, by FDG PET; 54%, 85%, and 73%, respectively, by prospective interpretation of CT; and 50%, 83%, and 70%, respectively, by blinded observer interpretation of CT. Among patients suspected of having only locoregional disease recurrence (n = 33), 10 had unsuspected mediastinal or IM disease by FDG PET. CONCLUSION: FDG PET may uncover disease in these nodal regions not recognized by conventional staging methods. Future prospective studies using histopathology for confirmation are needed to validate the preliminary findings of this retrospective study.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Fluordesoxiglucose F18 , Neoplasias do Mediastino/secundário , Compostos Radiofarmacêuticos , Adulto , Idoso , Biópsia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama Masculina/diagnóstico por imagem , Neoplasias da Mama Masculina/metabolismo , Neoplasias da Mama Masculina/patologia , Feminino , Fluordesoxiglucose F18/farmacocinética , Humanos , Processamento de Imagem Assistida por Computador , Metástase Linfática , Masculino , Neoplasias do Mediastino/diagnóstico por imagem , Neoplasias do Mediastino/metabolismo , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prevalência , Estudos Prospectivos , Compostos Radiofarmacêuticos/farmacocinética , Estudos Retrospectivos , Sensibilidade e Especificidade , Tomografia Computadorizada de Emissão , Tomografia Computadorizada por Raios X
11.
Clin Cancer Res ; 7(8): 2325-9, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11489808

RESUMO

PURPOSE: This study was designed to determine the efficacy and toxicity of cisplatin, etoposide, and paclitaxel (PET) in patients with extensive-stage small cell lung cancer (ES-SCLC). EXPERIMENTAL DESIGN: Chemo-naive adult patients with a performance status (PS) of 0-2 and adequate organ function were eligible. Patients received cisplatin 80 mg/m(2) i.v., etoposide 80 mg/m-2 i.v., and paclitaxel 175 mg/m(2) i.v. over a 3-h period on day 1 followed by etoposide 160 mg/m(2) p.o. on days 2 and 3 every 21 days for six cycles. G-CSF 5 microg/kg was injected s.c. on days 4-14. RESULTS: Eighty-eight patients were assessable. The median age was 60 years; 50% were male, 78% had PS of 0-1, 28% had PS of 2, 53% had multiple sites, and 13% had brain involvement. The overall response rate was 57% with 10 (12%) of 84 patients achieving a complete response. Median progression-free survival was 6 months [95% confidence interval (CI), 5-7 months] with a median survival of 11 months (95% CI, 8-13 months) and a 1-year survival rate of 43% (95% CI, 33-54%). Six patients (7%) died from toxicity. Grade 5 toxicity occurred in 3 (14%) of 22 patients (with a PS of 2) versus 3 (5%) of 61 patients (with a PS of 0-1; P, not significant). Grade 4 neutropenia developed in 40% of patients. Grade 3 nonhematological toxicities were primarily nausea (20%), vomiting (16%), and fatigue (14%). CONCLUSION: The survival result achieved was superior to prior SWOG experiences; however, the toxic death rate was unacceptably high in PS-2 patients. These results provide the largest database for the ongoing randomized Intergroup trial comparing PET to cisplatin+etoposide in PS-0-1 patients with ES-SCLC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Anemia/induzido quimicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Células Pequenas/patologia , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Fadiga/induzido quimicamente , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Neutropenia/induzido quimicamente , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Análise de Sobrevida , Trombocitopenia/induzido quimicamente , Resultado do Tratamento , Vômito/induzido quimicamente
13.
J Clin Oncol ; 19(13): 3210-8, 2001 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-11432888

RESUMO

PURPOSE: This randomized trial was designed to determine whether paclitaxel plus carboplatin (PC) offered a survival advantage over vinorelbine plus cisplatin (VC) for patients with advanced non--small-cell lung cancer. Secondary objectives were to compare toxicity, tolerability, quality of life (QOL), and resource utilization. PATIENTS AND METHODS: Two hundred two patients received VC (vinorelbine 25 mg/m(2)/wk and cisplatin 100 mg/m(2)/d, day 1 every 28 days) and 206 patients received PC (paclitaxel 225 mg/m(2) over 3 hours with carboplatin area under the curve of 6, day 1 every 21 days). Patients completed QOL questionnaires at baseline, 13 weeks, and 25 weeks. Resource utilization forms were completed at five time points through 24 months. RESULTS: Patient characteristics were similar between the groups. The objective response rate was 28% in the VC arm and 25% in the PC arm. Median survival was 8 months in both arms, with 1-year survival rates of 36% and 38%, respectively. Grade 3 and 4 leukopenia (P =.002) and neutropenia (P =.008) occurred more frequently on the VC arm. Grade 3 nausea and vomiting were higher on the VC arm (P =.001, P =.007), and grade 3 peripheral neuropathy was higher on the PC arm (P <.001). More patients on the VC arm discontinued therapy because of toxicity (P =.001). No difference in QOL was observed. Overall costs on the PC arm were higher than on the VC arm because of drug costs. CONCLUSION: PC is equally efficacious as VC for the treatment of advanced non--small-cell lung cancer. PC is less toxic and better tolerated but more expensive than VC. New treatment strategies should be pursued.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Vimblastina/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/terapia , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Feminino , Recursos em Saúde/estatística & dados numéricos , Humanos , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Qualidade de Vida , Análise de Regressão , Taxa de Sobrevida , Estados Unidos/epidemiologia , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , Vinorelbina
14.
J Clin Oncol ; 19(11): 2875-82, 2001 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-11387360

RESUMO

PURPOSE: To prospectively evaluate the effectiveness, safety, and clinical benefits of once-weekly epoetin alfa therapy as an adjunct to chemotherapy in anemic cancer patients. PATIENTS AND METHODS: A total of 3,012 patients with nonmyeloid malignancies who received chemotherapy were enrolled onto this multicenter, open-label, nonrandomized study conducted in 600 United States community-based practices. Patients received epoetin alfa 40,000 U once weekly, which could be increased to 60,000 U once weekly after 4 weeks dependent on hemoglobin response. Treatment was continued for a maximum of 16 weeks. RESULTS: Among the 2,964 patients assessable for efficacy, epoetin alfa therapy resulted in significant increases in hemoglobin levels, decreases in transfusion requirements, and improvements in functional status and fatigue as assessed by the linear analog scale assessment (energy level, ability to perform daily activities, and overall quality of life) and the anemia subscale of the Functional Assessment of Cancer Therapy-Anemia questionnaire. Improvements in quality-of-life parameters correlated significantly (P <.001) with increased hemoglobin levels. The direct relationship between hemoglobin and quality-of-life improvement was sustained during the 16-week study period, which is similar to findings of large community-based trials of three-times-weekly dosing. Once-weekly epoetin alfa was well tolerated, with most adverse events attributed to the underlying disease or concomitant chemotherapy. CONCLUSION: The results from this large, prospective, community-based trial suggest that once-weekly epoetin alfa therapy increases hemoglobin levels, decreases transfusion requirements, and improves quality of life in patients with cancer and anemia who undergo concomitant chemotherapy. Based on the results of this study, the clinical benefits and the adverse event profile of once-weekly epoetin alfa therapy in community-based practice are similar to those observed in the historical experience with the three-times-weekly dosage schedule.


Assuntos
Anemia/tratamento farmacológico , Antineoplásicos/efeitos adversos , Eritropoetina/farmacologia , Hematínicos/farmacologia , Atividades Cotidianas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia/patologia , Antineoplásicos/uso terapêutico , Transfusão de Sangue , Esquema de Medicação , Epoetina alfa , Eritropoetina/administração & dosagem , Fadiga , Feminino , Hematínicos/administração & dosagem , Hemoglobinas/análise , Humanos , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Estudos Prospectivos , Qualidade de Vida , Proteínas Recombinantes , Resultado do Tratamento
15.
AIDS Care ; 13(2): 157-62, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11304420

RESUMO

Cluster analysis was utilized to derive sub-types from a group of 53 males with HIV infection based on scores from several psychological measures. Measures administered included the Beck Depression Inventory, Life Orientation Test, Rosenberg Self-Esteem Test and the Internal Control Index. Three sub-types were identified: (1) average performing sub-type (2) severely dysfunctional sub-type, and (3) highly adaptive sub-type. All three sub-types showed different levels and patterns of test performance. Results are discussed in terms of sub-type characteristics and potential treatment issues.


Assuntos
Infecções por HIV/psicologia , Adaptação Psicológica , Adulto , Análise por Conglomerados , Depressão , Infecções por HIV/imunologia , Infecções por HIV/terapia , Humanos , Contagem de Linfócitos , Masculino , Testes Psicológicos , Resultado do Tratamento
16.
J Clin Oncol ; 19(2): 448-57, 2001 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-11208838

RESUMO

PURPOSE: To determine the prognostic and predictive significance of p53 and K-ras mutations in patients with completely resected non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients were randomized preoperatively to receive adjuvant postoperative radiotherapy (Arm A) or radiotherapy plus concurrent chemotherapy (Arm B). p53 protein expression was studied by immunohistochemistry (IHC) and p53 mutations in exons 5 to 8 were evaluated by single-strand conformational analysis. K-ras mutations in codons 12, 13, and 61 were determined using engineered restriction fragment length polymorphisms. RESULTS: Four hundred eighty-eight patients were entered onto E3590; 197 tumors were assessable for analysis. Neither presence nor absence of p53 mutations, p53 protein expression, or K-ras mutations correlated with survival or progression-free survival. There was a trend toward improved survival for patients with wildtype K-ras (median, 42 months) compared with survival of patients with mutant K-ras who were randomized to chemotherapy plus radiotherapy (median, 25 months; P = .09). Multivariate analysis revealed only age and tumor stage to be significant prognostic factors, although there was a trend bordering on statistical significance for K-ras (P = .066). Analysis of survival difference by p53 by single-stranded conformational polymorphism and IHC, interaction of p53 and K-ras, interaction of p53 and treatment arm, nodal station, extent of surgery, weight loss, and histology did not reach statistical significance. CONCLUSION: p53 mutations and protein overexpression are not significant prognostic or predictive factors in resected stage II or IIIA NSCLC. K-ras mutations may be a weak prognostic marker. p53 or K-ras should not be routinely used in the clinical management of these patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Genes p53 , Genes ras , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Terapia Combinada , Análise Mutacional de DNA , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Análise Multivariada , Mutação , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Polimorfismo Conformacional de Fita Simples , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Análise de Sobrevida
18.
Cancer ; 89(9): 1953-60, 2000 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-11064352

RESUMO

BACKGROUND: Elderly patients comprise a significant portion of patients with limited stage small cell lung carcinoma. However, the prognostic importance of age has been controversial, and concern for toxicity often hinders enthusiasm for offering full dose therapy. METHODS: In this retrospective analysis of Intergroup Trial 0096, the authors compared the outcome of patients 70 years or older to those younger than 70 years. Patients received cisplatin 60 mg/m(2), Day 1 and etoposide 120 mg/m(2), Days 1-3 for 4 cycles and either once or twice daily concurrent thoracic radiotherapy to 45 grays. RESULTS: Of 381 patients, 50 (13%) were age 70 years or older. The elderly group did not differ significantly from those younger than 70 years with respect to gender distribution, performance status, or weight loss. Severe hematologic toxicity (Grade 4-5: 61% vs. 84%; P < 0.01) and fatal toxicity (1% vs. 10%; P = 0.01) occurred more often among older patients. There were no differences in the frequency of nonhematologic toxicities. Response rate (88% vs. 80%; P = 0.11), event free survival rate (5 year, 19% vs. 16%; P = 0.18), time to local failure, and duration of response did not differ between groups. Overall survival rates (5 year, 22% vs. 16%; P = 0.05) favored those younger than 70 years. Much of the difference in overall survival rates between age groups occurred within the first 6 months on study. CONCLUSIONS: Elderly patients had similar response and survival rates compared with those younger than 70 years. However, toxicity, particularly hematologic, was greater among the elderly. Selected older patients, such as those with a good performance status, should be considered for optimum treatment approaches.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Pequenas/tratamento farmacológico , Carcinoma de Células Pequenas/radioterapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Fatores Etários , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/administração & dosagem , Ensaios Clínicos como Assunto , Terapia Combinada/efeitos adversos , Etoposídeo/administração & dosagem , Feminino , Humanos , Masculino , Dosagem Radioterapêutica , Estudos Retrospectivos , Taxa de Sobrevida
19.
N Engl J Med ; 343(17): 1217-22, 2000 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-11071672

RESUMO

BACKGROUND: We conducted a randomized trial to determine whether combination chemotherapy plus thoracic radiotherapy is superior to thoracic radiotherapy alone in prolonging survival and preventing local recurrence in patients with completely resected stage II or IIIa non-small-cell lung cancer. METHODS: After surgical staging and resection of the tumor (usually by lobectomy or pneumonectomy), the patients were randomly assigned to receive either four 28-day cycles of cisplatin (60 mg per square meter of body-surface area intravenously on day 1) and etoposide (120 mg per square meter intravenously on days 1, 2, and 3) administered concurrently with radiotherapy (a total of 50.4 Gy, given in 28 daily fractions) or radiotherapy alone (a total of 50.4 Gy, given in 28 daily fractions). RESULTS: Of the 488 patients who were enrolled in the study, 242 were assigned to receive radiotherapy alone and 246 were assigned to receive chemotherapy and radiotherapy. The median duration of follow-up was 44 months. Treatment-associated mortality was 1.2 percent in the group given radiotherapy alone and 1.6 percent in the group given chemotherapy and radiotherapy. The median survival was 39 months in the group given radiotherapy and 38 months in the group given chemotherapy and radiotherapy (P= 0.56 by the log-rank test). The relative likelihood of survival among patients assigned to receive chemotherapy and radiotherapy, as compared with those assigned to receive radiotherapy alone, was 0.93 (95 percent confidence interval, 0.74 to 1.18). Intrathoracic disease recurred within the radiation field in 30 of 234 patients (13 percent) in the group given radiotherapy and in 28 of 236 patients (12 percent) in the group given chemotherapy and radiotherapy (P=0.84); data on recurrence were not available for 18 patients. CONCLUSIONS: As compared with radiotherapy alone, adjuvant radiotherapy and chemotherapy with cisplatin and etoposide does not decrease the risk of intrathoracic recurrence or prolong survival in patients with completely resected stage II or IIIa non-small-cell lung cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/terapia , Recidiva Local de Neoplasia/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Modelos de Riscos Proporcionais , Radioterapia Adjuvante , Risco , Análise de Sobrevida
20.
Percept Mot Skills ; 91(2): 675-82, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11065331

RESUMO

This study presents a data set for a reference group on the Reitan-Indiana Neuropsychological Test Battery for Young Children. The data set is based on a sample of 224 children, ages 5 to 8 years, referred to a special services cooperative for academic or behavioral concerns during the years 1980 through 1993. Data are presented in terms of sample size, means, standard deviations, diagnostic classifications, and population characteristics. Previously published data sets are reviewed in comparison to this newly acquired data set. Potential advantages of this data set include the larger sample, contemporary data collection, and a sample drawn from a United States school-referred population.


Assuntos
Transtornos do Comportamento Infantil/diagnóstico , Deficiências da Aprendizagem/diagnóstico , Testes Neuropsicológicos/estatística & dados numéricos , Criança , Transtornos do Comportamento Infantil/psicologia , Pré-Escolar , Feminino , Humanos , Deficiências da Aprendizagem/psicologia , Masculino , Psicometria , Valores de Referência , Reprodutibilidade dos Testes
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