RESUMO
BACKGROUND: This phase III open-label trial investigated the efficacy of nilotinib in patients with advanced gastrointestinal stromal tumors following prior imatinib and sunitinib failure. PATIENTS AND METHODS: Patients were randomized 2:1 to nilotinib 400 mg b.i.d. or best supportive care (BSC; BSC without tyrosine kinase inhibitor, BSC+imatinib, or BSC+sunitinib). Primary efficacy end point was progression-free survival (PFS) based on blinded central radiology review (CRR). Patients progressing on BSC could cross over to nilotinib. RESULTS: Two hundred and forty-eight patients enrolled. Median PFS was similar between arms (nilotinib 109 days, BSC 111 days; P=0.56). Local investigator-based intent-to-treat (ITT) analysis showed a significantly longer median PFS with nilotinib (119 versus 70 days; P=0.0007). A trend in longer median overall survival (OS) was noted with nilotinib (332 versus 280 days; P=0.29). Post hoc subset analyses in patients with progression and only one prior regimen each of imatinib and sunitinib revealed a significant difference in median OS of >4 months in favor of nilotinib (405 versus 280 days; P=0.02). Nilotinib was well tolerated. CONCLUSION: In the ITT analysis, no significant difference in PFS was observed between treatment arms based on CRR. In the post hoc subset analyses, nilotinib provided significantly longer median OS.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Gastrointestinais/tratamento farmacológico , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Indóis/uso terapêutico , Piperazinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Pirróis/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Benzamidas , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos , Feminino , Neoplasias Gastrointestinais/mortalidade , Neoplasias Gastrointestinais/patologia , Tumores do Estroma Gastrointestinal/mortalidade , Tumores do Estroma Gastrointestinal/patologia , Humanos , Mesilato de Imatinib , Indóis/efeitos adversos , Indóis/farmacologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos , Piperazinas/efeitos adversos , Piperazinas/farmacologia , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/farmacocinética , Proteínas Tirosina Quinases/antagonistas & inibidores , Pirimidinas/efeitos adversos , Pirimidinas/farmacocinética , Pirimidinas/farmacologia , Pirróis/efeitos adversos , Pirróis/farmacologia , Sunitinibe , Resultado do Tratamento , Adulto JovemRESUMO
GaAs nanowires were heated locally under ambient air conditions by a focused laser beam which led to oxidation and formation of crystalline arsenic on the nanowire surface. Atomic force microscopy, photoluminescence and Raman spectroscopy experiments were performed on the same single GaAs nanowires in order to correlate their structural and optical properties. We show that the local changes of the nanowires act as a barrier for thermal transport which is of interest for thermoelectric applications.
RESUMO
The purpose of this study was to determine the efficacy of and tolerance to antithymocyte globulin (ATG)-based therapy in patients with myelodysplastic syndrome (MDS). Therapy consisted of ATG 40 mg/kg/day daily intravenously (i.v.) for 4 days; cyclosporine daily orally for 6 months with levels titrated between 200 and 400 mg/dl; and methylprednisone 1 mg/kg i.v. daily before each dose of ATG. Of 32 patients treated, 31 patients were evaluable. The median age was 59 years (range, 28-79 years). A total of 18 patients had refractory anemia (RA) or RA with ringed sideroblasts (RARS), 10 patients had RA with excess blasts (RAEB), two patients had RAEB in transformation, and one patient had chronic myelomonocytic leukemia. ATG, cyclosporine, and methylprednisone induced complete (N=4) or partial (N=1) remission in five patients (16% of total; RA, two patients; RARS, two patients; and RAEB, one patient). Durable complete remissions were observed in three of 18 patients (17%) with RA (N=1) or RARS (N=2) (12, 41+, and 60+ months). The most common adverse events were fever and allergic reactions. Hepatic and renal dysfunction, albeit consistently reversible, occurred in 19 and 13% of the patients, respectively. In conclusion, an ATG-based regimen can produce durable complete remissions in a subset of patients with MDS.
Assuntos
Soro Antilinfocitário/uso terapêutico , Imunossupressores/uso terapêutico , Síndromes Mielodisplásicas/tratamento farmacológico , Adulto , Idoso , Transfusão de Sangue , Ciclosporina/uso terapêutico , Feminino , Hematócrito , Humanos , Cariotipagem , Masculino , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/sangue , Síndromes Mielodisplásicas/genética , Contagem de Plaquetas , Resultado do TratamentoRESUMO
BACKGROUND: Several recent reports have suggested that patients with non-Hodgkin's lymphomas (NHL) who undergo autologous stem cell transplantation (ASCT) are at increased risk of developing therapy-related myelodysplastic syndrome (tMDS) and acute myelogenous leukemia (tAML). PATIENTS AND METHODS: We analyzed 493 patients with NHL who underwent ASCT at The University of Texas M.D. Anderson Cancer Center between January 1990 and August 1999. RESULTS: With a median follow-up time of 21 months after HDT, 22 patients developed persistent cytopenia in at least one cell line with morphologic or cytogenetic evidence of tMDS or tAML. Univariate analysis identified prior fludarabine therapy, bone marrow involvement with lymphoma, and total body irradiation (TBI) as significant risk factors for the development of tMDS/tAML (P <0.05). Multiple logistic regression analysis showed that TBI was independently associated with an increased risk of developing tMDS/tAML (P <0.01). Further analysis of the patients who received TBI revealed that patients receiving TBI in combination with cyclophosphamide and etoposide were more likely to develop tMDS/tAML than those who received TBI with cyclophosphamide or thiotepa (P <0.01). The median survival of patients developing tMDS/tAML was 7.5 months (range 0-32 months). CONCLUSIONS: TBI, especially when used in combination with cyclophosphamide and etoposide as the pretransplant conditioning regimen, is a significant risk factor for the development of tMDS/tAML.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia Mieloide/etiologia , Linfoma não Hodgkin/terapia , Síndromes Mielodisplásicas/etiologia , Segunda Neoplasia Primária/etiologia , Doença Aguda , Adolescente , Adulto , Idoso , Feminino , Humanos , Incidência , Leucemia Mieloide/diagnóstico , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/epidemiologia , Segunda Neoplasia Primária/diagnóstico , Segunda Neoplasia Primária/tratamento farmacológico , Avaliação de Resultados em Cuidados de Saúde , Fatores de Risco , Taxa de Sobrevida , Transplante Autólogo/efeitos adversosRESUMO
PURPOSE: To evaluate the outcome of high-dose chemotherapy (HDCT) and autologous or allogeneic hematopoietic transplantation in patients with peripheral T-cell lymphoma (PTCL) who experienced disease recurrence after prior conventional chemotherapy. PATIENTS AND METHODS: We performed a retrospective analysis of 36 PTCL patients from the University of Texas M.D. Anderson Cancer Center treated between 1989 and 1998 with HDCT and autologous or allogeneic hematopoietic transplantation. RESULTS: A total of 36 patients were studied (29 received autologous transplantation, and seven received allogeneic transplantation). The overall survival rate at 3 years was 36% (95% confidence interval [CI], 23% to 59%), and the progression-free survival (PFS) rate was 28% (95% CI, 16% to 49%). The pretransplant serum lactate dehydrogenase level was the most important prognostic factor for both survival and PFS rates (P < .001). A Pretransplant International Prognostic Index score of < or = 1 indicated a superior survival rate (P = .036) but not an improved PFS rate. A median follow-up of 43 months (range, 13 to 126 months) showed 13 patients (36%) were still alive with no evidence of disease. CONCLUSION: Our results are comparable to the published data on HDCT in B-cell non-Hodgkin's lymphoma (NHL) patients despite the fact that patients with PTCL are known to have a worse outcome compared with B-cell NHL patients. Considering the dismal outcome of conventional chemotherapy in PTCL patients, these data suggest the hypothesis that the poor prognostic implication of T-cell phenotyping in NHL might be overcome by frontline HDCT and transplantation.