Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 8 de 8
Filtrar
1.
Br J Dermatol ; 161(3): 660-3, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19438862

RESUMO

BACKGROUND: Primary cutaneous T-cell lymphomas (CTCLs) are malignancies characterized by a clonal T-cell infiltrate involving the skin. CTCLs often show resistance to conventional antineoplastic chemotherapy. Gemcitabine is a pyrimidine analogue which has shown efficacy and a favourable safety profile in solid tumours and haematological malignancies. OBJECTIVES: We report a multicentre retrospective study of 23 patients who received gemcitabine for advanced-stage CTCL and emphasize the high incidence of serious unusual adverse events. METHODS: We collected data from 23 patients with refractory CTCL (14 mycosis fungoides, six Sézary syndrome and three other CTCL). Gemcitabine was given weekly within a 21- or 28-day schedule. Response was evaluated after three and six cycles of chemotherapy. For each patient, all adverse events were recorded. RESULTS: Of the 16 patients who received at least three cycles of gemcitabine, 10 achieved a response (62.5%). Only five patients reached the sixth cycle of treatment and four still had a favourable response. Haematological toxicity was recorded in 15 cases with severe grade 3 or 4 neutropenia in seven patients (30%) and six serious infections (26%). Other serious adverse events were observed in six cases (26%): one haemolytic-uraemic syndrome, one severe capillary leak syndrome, one acute heart failure related to cardiac arrhythmia, two bullous and erosive dermatitis, and one recurrent influenza-like syndrome with altered general condition. CONCLUSIONS: Our study confirms the early efficacy of gemcitabine in advanced-stage CTCL. However, our results contradict the safety profile of gemcitabine previously reported and underline the high incidence of severe complications including visceral and cutaneous involvement.


Assuntos
Antineoplásicos/uso terapêutico , Desoxicitidina/análogos & derivados , Linfoma Cutâneo de Células T/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Feminino , Humanos , Linfoma Cutâneo de Células T/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Cutâneas/patologia , Vimblastina/administração & dosagem , Vimblastina/análogos & derivados , Vinorelbina , Gencitabina
3.
Leukemia ; 18(4): 670-5, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-14762443

RESUMO

Acute respiratory failure and infectious pneumonia are the major causes of death during induction chemotherapy of acute leukemia. However, the causes, incidence and prognostic value of all respiratory events (REs) occurring in this context have never been assessed prospectively. We recruited 65 consecutive patients with newly diagnosed acute leukemia into a 1-year prospective study (December 2000-November 2001) to evaluate the incidence and prognostic value of these events. REs were frequent: 38 were recorded in 30 patients. There was a significant relationship between REs and pre-existing respiratory disease and/or smoking. REs were caused by infection in 34% of cases, by an established cause other than infection in 42% and had an undetermined cause in 24%. Poor early outcome (death within 45 days of starting induction chemotherapy) in patients experiencing an RE was independently associated with a >25/min respiratory rate (P=0.003) and the nonachievement of complete remission (CR) (P<0.0001). Predictors of overall survival in the entire patient population were the absence of CR (P<0.0001), REs (P=0.02) and a > or =2 performance status (P=0.03). In conclusion, REs are frequent during induction chemotherapy of acute leukemia and represent an independent prognostic factor of poor outcome, regardless of their cause.


Assuntos
Leucemia/complicações , Leucemia/diagnóstico , Transtornos Respiratórios/etiologia , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Infecciosos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Incidência , Leucemia/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Indução de Remissão , Transtornos Respiratórios/epidemiologia , Fatores de Risco , Taxa de Sobrevida
4.
Leukemia ; 18(7): 1246-51, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15116123

RESUMO

The multidrug resistance (MDR) phenotype, induced by the overexpression of several ABC transporters or by antiapoptotic mechanisms, has been identified as the major cause of drug resistance in the treatment of patients with acute myeloid leukemia (AML). In this study, we have shown that valproic acid (VPA) (a histone deacetylase inhibitor) can inhibit the proliferation of both P-glycoprotein (P-gp)- and MDR-associated protein 1 (MRP1)-positive and -negative cells. VPA also induced apoptosis of P-gp-positive cells. VPA induced apoptosis in K562 cells led to decrease in Flip (FLICE/caspase-8 inhibitory protein) expression with Flip cleavage, which could not be observed in HL60 cells. In HL60/MRP cell line, which proved to be resistant to apoptosis by VPA, we observed an abnormal expression of apoptotic regulatory proteins, overexpression of Bcl-2 and absence of Bax. Also, the Bcl-2 antagonist HA14-1 rapidly restored apoptosis in this cell line. Cotreatment with cytosine arabinoside induced very strong apoptosis in both K562/DOX and HL60/DNR cell lines. VPA also induced apoptosis in AML patient cells expressing P-gp and/or MRP1. Our findings show VPA as an interesting drug that should be tested in clinical trials for overcoming the MDR phenotype in AML patients.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/análise , Apoptose/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intracelular , Leucemia Mieloide/tratamento farmacológico , Proteínas Associadas à Resistência a Múltiplos Medicamentos/análise , Ácido Valproico/farmacologia , Doença Aguda , Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD , Proteínas de Transporte/metabolismo , Divisão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Citarabina/farmacologia , Avaliação Pré-Clínica de Medicamentos , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Sinergismo Farmacológico , Inibidores Enzimáticos/farmacologia , Humanos , Leucemia Mieloide/metabolismo , Leucemia Mieloide/patologia , Células Tumorais Cultivadas
7.
Leukemia ; 22(7): 1361-7, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18432262

RESUMO

In patients with hematological malignancy (HM) developing acute respiratory failure (ARF) bronchoalveolar lavage (BAL) is considered as a major diagnostic tool. However, the benefit/risk ratio of this invasive procedure is probably lower in the subset of patients with acute myeloid leukemia (AML). The study was to analyze the yield of BAL performed in HM patients (n=175) with AML or lymphoid malignancies (LM) admitted in intensive care unit (ICU) for ARF and pulmonary infiltrates. BAL was performed in 121 patients (53/73 AML patients (73%) and 68/102 LM patients (67%)) without a definite diagnosis at admission or contraindication for fiberoptic bronchoscopy. Life-threatening complications were noticed in 12/121 patients (10%). The overall diagnostic yield of BAL was 47% (25/53) in AML patients and 50% (34/68) in LM patients. A microorganism was recovered from BAL in 23% (12/53) of AML patients and 41% (28/68) of LM patients (P<0.005). BAL results induced significant therapeutic changes in 17% (9/53) of AML patients vs 35% (24/68) of LM patients (P=0.039). This study underlines the rather low diagnostic yield of BAL for infectious diagnosis and the low rate of therapeutic changes induced by its results in AML patients with ARF admitted in ICU.


Assuntos
Lavagem Broncoalveolar/métodos , Unidades de Terapia Intensiva , Leucemia Mieloide Aguda/complicações , Pneumonia/diagnóstico , Insuficiência Respiratória/diagnóstico , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Lavagem Broncoalveolar/efeitos adversos , Broncoscopia/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Insuficiência Respiratória/mortalidade
8.
Br J Cancer ; 95(3): 253-9, 2006 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-16847470

RESUMO

To determine the maximum-tolerated dose (MTD), dose-limiting toxicities and pharmacokinetic of semisynthetic homoharringtonine (ssHHT), given as a twice daily subcutaneous (s.c.) injections for 9 days, in patients with advanced acute leukaemia, 18 patients with advanced acute myeloid leukaemia were included in this sequential Bayesian phase I dose-finding trial. A starting dose of 0.5 mg m(-2) day(-1) was explored with subsequent dose escalations of 1, 3, 5 and 6 mg m(-2) day(-1). Myelosuppression was constant. The MTD was estimated as the dose level of 5 mg m(-2) day(-1) for 9 consecutive days by s.c. route. Dose-limiting toxicities were hyperglycaemia with hyperosmolar coma at 3 mg m(-2), and (i) one anasarque and haematemesis, (ii) one life-threatening pulmonary aspergillosis, (iii) one skin rash and (iv) one scalp pain at dose level of 5 mg m(-2) day(-1). The mean half-life of ssHHT was 11.01+/-3.4 h, the volume of distribution at steady state was 2+/-1.4 l kg(-1) and the plasma clearance was 11.6+/-10.4 l h(-1). Eleven of the 12 patients with circulating leukaemic cells had blood blast clearance, two achieved complete remission and one with blast crisis of CMML returned in chronic phase. The recommended daily dose of ssHHT on the 9-day schedule is 5 mg m(-2) day(-1).


Assuntos
Harringtoninas/administração & dosagem , Harringtoninas/farmacocinética , Leucemia Mieloide/tratamento farmacológico , Doença Aguda , Adulto , Idoso , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Harringtoninas/efeitos adversos , Mepesuccinato de Omacetaxina , Humanos , Injeções Subcutâneas , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Indução de Remissão , Taxa de Sobrevida , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA