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1.
J Natl Cancer Inst ; 110(1)2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-28922787

RESUMO

Background: The optimal duration of extended endocrine therapy beyond five years after initial aromatase inhibitor-based adjuvant therapy for postmenopausal women with hormone receptor-positive breast cancer is still unknown. Therefore, we conducted a clinical trial to compare two different extended endocrine therapy durations. Methods: In the randomized phase III IDEAL trial, postmenopausal patients with hormone receptor-positive breast cancer were randomly allocated to either 2.5 or five years of letrozole after the initial five years of any endocrine therapy. The primary end point was disease free survival (DFS), and secondary end points were overall survival (OS), distant metastasis-free interval (DMFi), new primary breast cancer, and safety. Hazard ratios (HRs) were determined using Cox regression analysis. All analyses were by intention-to-treat principle. Results: A total of 1824 patients were assigned to either 2.5 years (n = 909) or five years (n = 915) of letrozole, with a median follow-up of 6.6 years. A DFS event occurred in 152 patients in the five-year group, compared with 163 patients in the 2.5-year group (HR = 0.92, 95% confidence interval [CI] = 0.74 to 1.16). OS (HR = 1.04, 95% CI = 0.78 to 1.38) and DMFi (HR = 1.06, 95% CI = 0.78 to 1.45) were not different between both groups. A reduction in occurrence of second primary breast cancer was observed with five years of treatment (HR = 0.39, 95% CI = 0.19 to 0.81). Subgroup analysis did not identify patients who benefit from five-year extended therapy. Conclusion: This study showed no superiority of five years over 2.5 years of extended adjuvant letrozole after an initial five years of adjuvant endocrine therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/terapia , Carcinoma Intraductal não Infiltrante/terapia , Recidiva Local de Neoplasia/prevenção & controle , Segunda Neoplasia Primária/prevenção & controle , Nitrilas/administração & dosagem , Triazóis/administração & dosagem , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Inibidores da Aromatase/administração & dosagem , Neoplasias da Mama/química , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/química , Carcinoma Ductal de Mama/prevenção & controle , Carcinoma Ductal de Mama/secundário , Carcinoma Intraductal não Infiltrante/prevenção & controle , Quimioterapia Adjuvante/efeitos adversos , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Letrozol , Mastectomia Segmentar , Pessoa de Meia-Idade , Nitrilas/efeitos adversos , Pós-Menopausa , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Taxa de Sobrevida , Tamoxifeno/administração & dosagem , Fatores de Tempo , Triazóis/efeitos adversos
3.
J Clin Oncol ; 33(35): 4176-87, 2015 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-26527776

RESUMO

PURPOSE: The MOSAIC (Multicenter International Study of Oxaliplatin/Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer) study has demonstrated 3-year disease-free survival (DFS) and 6-year overall survival (OS) benefit of adjuvant oxaliplatin in stage II to III resected colon cancer. This update presents 10-year OS and OS and DFS by mismatch repair (MMR) status and BRAF mutation. METHODS: Survival actualization after 10-year follow-up was performed in 2,246 patients with resected stage II to III colon cancer. We assessed MMR status and BRAF mutation in 1,008 formalin-fixed paraffin-embedded specimens. RESULTS: After a median follow-up of 9.5 years, 10-year OS rates in the bolus/infusional fluorouracil plus leucovorin (LV5FU2) and LV5FU2 plus oxaliplatin (FOLFOX4) arms were 67.1% versus 71.7% (hazard ratio [HR], 0.85; P = .043) in the whole population, 79.5% versus 78.4% for stage II (HR, 1.00; P = .980), and 59.0% versus 67.1% for stage III (HR, 0.80; P = .016) disease. Ninety-five patients (9.4%) had MMR-deficient (dMMR) tumors, and 94 (10.4%) had BRAF mutation. BRAF mutation was not prognostic for OS (P = .965), but dMMR was an independent prognostic factor (HR, 2.02; 95% CI, 1.15 to 3.55; P = .014). HRs for DFS and OS benefit in the FOLFOX4 arm were 0.48 (95% CI, 0.20 to 1.12) and 0.41 (95% CI, 0.16 to 1.07), respectively, in patients with stage II to III dMMR and 0.50 (95% CI, 0.25 to 1.00) and 0.66 (95% CI, 0.31 to 1.42), respectively, in those with BRAF mutation. CONCLUSION: The OS benefit of oxaliplatin-based adjuvant chemotherapy, increasing over time and with the disease severity, was confirmed at 10 years in patients with stage II to III colon cancer. These updated results support the use of FOLFOX in patients with stage III disease, including those with dMMR or BRAF mutation.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Reparo de Erro de Pareamento de DNA , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Quimioterapia Adjuvante , Neoplasias do Colo/genética , Neoplasias do Colo/mortalidade , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Ácido Glutâmico , Humanos , Infusões Intravenosas , Injeções Intravenosas , Estimativa de Kaplan-Meier , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Razão de Chances , Compostos Organoplatínicos/administração & dosagem , Prognóstico , Resultado do Tratamento , Valina
4.
Ann Clin Biochem ; 50(Pt 2): 169-72, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23467067

RESUMO

Lactic acidosis is a rare complication of haematological malignancies with a poor prognostic outcome and unclear aetiology. Possible mechanisms include high rate of glycolysis by cancer cells, in part due to over-expression of hexokinase II. The insulin-like growth factor (IGF)-system has an important role in normal as well as tumour cell growth. We present a case of a 79-year-old man with a diffuse large B-cell lymphoma and lactic acidosis. Initially, the patient was successfully treated according to the R-CHOP scheme. After recurrence of disease, the patient was treated according to a protocol of the Dutch-Belgian Haemato-Oncology Group (HOVON-85 study). Eleven months after completion of the last therapy, the patient still appeared to be in complete remission. Serum levels of IGFs, pro-IGF-IIE[68-88], IGF binding proteins (IGFBPs)-1 to -4, acid labile subunit (ALS), as well as ternary IGF-I-IGFBP-3-ALS complex formation, were determined in samples taken before, during and after treatment, respectively. Before treatment patient's serum concentration of the growth hormone-dependent parameters of the IGF-system and IGF-II were clearly reduced when compared with patient's values during remission of disease. On the other hand, during acidosis a relatively higher proportion of IGFs is present in binary complexes, instead of 150 kDa complexes, that may allow an increased access of IGFs to target cells including the malignant ones. Pretreatment serum levels of IGFBP-1 and -2 were elevated, decreased during therapy and normalized at remission. Especially IGFBP-2 seems a suitable marker for disease activity.


Assuntos
Acidose Láctica/complicações , Linfoma Difuso de Grandes Células B/sangue , Linfoma Difuso de Grandes Células B/complicações , Somatomedinas/metabolismo , Idoso , Humanos , Linfoma Difuso de Grandes Células B/terapia , Masculino
5.
Eur J Cancer ; 47(15): 2273-81, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21741829

RESUMO

BACKGROUND: Continuation of trastuzumab plus capecitabine (XH) showed a significantly improved overall response rate and time to progression compared with capecitabine (X) alone in women with HER2-positive breast cancer progressing during trastuzumab treatment. Here, we report the final analysis on overall survival. PATIENTS AND METHODS: Patients with HER2-positive, advanced breast cancer who progressed during treatment with trastuzumab with or without 1st-line metastatic chemotherapy were prospectively randomised to X (2500mg/m(2) on days 1-14, q3w) or XH (6 (8)mg/kg, q3w). Overall survival was a pre-specified secondary end-point. RESULTS: Median follow-up at June 2010 was 20.7months. Fifty nine of 74 and 60 of 77 patients died in the X and XH arm, respectively. Median overall survival was 20.6 and 24.9months with X and XH, respectively (HR=0.94 [0.65-1.35]; p=0.73). Performance status and metastatic site were independent prognosticators for overall survival. No difference between treatment arms was observed for patients who achieved clinical response or clinical benefit, respectively. Patients who continued/restarted anti-HER2 treatment (trastuzumab or lapatinib) after 2nd progression (N=52) had a post-progression survival of 18.8 compared with 13.3months for those who did not receive 3rd line treatment with anti-HER2 agents (N=88) (HR 0.63; p=0.02). CONCLUSIONS: Final overall survival analysis of the GBG-26 study did not demonstrate a significant survival benefit for treatment beyond progression with trastuzumab. However, in a post-hoc analysis, patients receiving anti-HER2 treatment as 3rd line therapy showed a better post-progression survival than those not receiving this targeted treatment.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Receptor ErbB-2/antagonistas & inibidores , Anticorpos Monoclonais Humanizados/administração & dosagem , Neoplasias da Mama/enzimologia , Neoplasias da Mama/patologia , Capecitabina , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Europa (Continente) , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/análogos & derivados , Humanos , Estimativa de Kaplan-Meier , Terapia de Alvo Molecular , Modelos de Riscos Proporcionais , Estudos Prospectivos , Receptor ErbB-2/metabolismo , Medição de Risco , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo , Trastuzumab , Resultado do Tratamento
6.
J Clin Oncol ; 27(12): 1999-2006, 2009 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-19289619

RESUMO

PURPOSE: Trastuzumab shows clinical activity in human epidermal growth factor receptor 2 (HER-2)-positive early and advanced breast cancer. In the German Breast Group 26/Breast International Group 03-05 trial, we investigated if trastuzumab treatment should be continued beyond progression. METHODS: Patients with HER-2-positive breast cancer that progresses during treatment with trastuzumab were randomly assigned to receive capecitabine (2,500 mg/m(2) body-surface area on days 1 through 14 [1,250 mg/m(2) semi-daily]) alone or with continuation of trastuzumab (6 mg/kg body weight) in 3-week cycles. The primary end point was time to progression. RESULTS: We randomly assigned 78 patients to capecitabine and 78 patients to capecitabine plus trastuzumab. Sixty-five events and 38 deaths in the capecitabine group and 62 events and 33 deaths in the capecitabine-plus-trastuzumab group occurred during 15.6 months of follow-up. Median times to progression were 5.6 months in the capecitabine group and 8.2 months in the capecitabine-plus-trastuzumab group with an unadjusted hazard ratio of 0.69 (95% CI, 0.48 to 0.97; two-sided log-rank P = .0338). Overall survival rates were 20.4 months (95% CI, 17.8 to 24.7) in the capecitabine group and 25.5 months (95% CI, 19.0 to 30.7) in the capecitabine-plus-trastuzumab group (P = .257). Overall response rates were 27.0% with capecitabine and 48.1% with capecitabine plus trastuzumab (odds ratio, 2.50; P = .0115). Continuation of trastuzumab beyond progression was not associated with increased toxicity. CONCLUSION: Continuation of trastuzumab plus capecitabine showed a significant improvement in overall response and time to progression compared with capecitabine alone in women with HER-2-positive breast cancer who experienced progression during trastuzumab treatment.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Receptor ErbB-2/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Neoplasias da Mama/patologia , Capecitabina , Quimioterapia Adjuvante , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Progressão da Doença , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/análogos & derivados , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Agências Internacionais , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo , Trastuzumab , Resultado do Tratamento
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