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1.
Br J Haematol ; 143(2): 201-9, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18691173

RESUMO

The epothilones represent a novel group of microtubule stabilization agents that appear to retain activity even in chemotherapy-resistant cell lines and animal models. Because of their ability to overcome chemotherapy resistance, we conducted a phase II study of Ixabepilone in patients with indolent non-Hodgkin lymphoma and mantle cell lymphoma (MCL). Ixabepilone was given at a dose of 25 mg/m(2) weekly for three of four consecutive weeks. Patients were required to have received < or =4 prior chemotherapy regimens, with an interval of at least one month since the last treatment, 3 months from prior rituximab, and 7 d from prior steroids, an absolute neutrophil count >1 x 10(9)/l and a platelet count >50 x 10(9)/l. Dose reductions were allowed. The overall response rate in assessable patients was 27% in this otherwise heavily treated population. One patient with chemotherapy-refractory follicular lymphoma attained a complete remission that lasted approximately 8 months. Three responses were also seen in refractory MCL and one in small lymphocytic lymphoma. The duration of response ranged from 2 to 8 months. Major toxicities included fatigue, myelosuppression and neuropathy. These data suggest that Ixabepilone has activity in chemotherapy-refractory lymphoma.


Assuntos
Antineoplásicos/uso terapêutico , Epotilonas/uso terapêutico , Linfoma de Célula do Manto/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Esquema de Medicação , Eletromiografia , Epotilonas/efeitos adversos , Feminino , Humanos , Linfoma Folicular/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Neurônios Motores , Condução Nervosa , Recidiva , Indução de Remissão , Células Receptoras Sensoriais , Resultado do Tratamento
2.
J Clin Oncol ; 23(4): 676-84, 2005 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-15613699

RESUMO

PURPOSE: To determine the antitumor activity of the novel proteasome inhibitor bortezomib in patients with indolent and mantle-cell lymphoma (MCL). PATIENTS AND METHODS: Patients with indolent and MCL were eligible. Bortezomib was given at a dose of 1.5 mg/m2 on days 1, 4, 8, and 11. Patients were required to have received no more than three prior chemotherapy regimens, with at least 1 month since the prior treatment, 3 months from prior rituximab, and 7 days from prior corticosteroids; absolute neutrophil count more than 1,500/microL (500/microL if documented bone marrow involvement); and platelet count more than 50,000/microL. RESULTS: Twenty-six patients were registered, of whom 24 were assessable. Ten patients had follicular lymphoma, 11 had MCL, three had small lymphocytic lymphoma (SLL) or chronic lymphocytic leukemia (CLL), and two had marginal zone lymphoma. The overall response rate was 58%, with one complete remission (CR), one unconfirmed CR (CRu), and four partial remissions (PR) among patients with follicular non-Hodgkin's lymphoma (NHL). All responses were durable, lasting from 3 to 24+ months. One patient with MCL achieved a CRu, four achieved a PR, and four had stable disease. One patient with MCL maintained his remission for 19 months. Both patients with marginal zone lymphoma achieved PR lasting 8+ and 11+ months, respectively. Patients with SLL or CLL have yet to respond. Overall, the drug was well tolerated, with only one grade 4 toxicity (hyponatremia). The most common grade 3 toxicities were lymphopenia (n = 14) and thrombocytopenia (n = 7). CONCLUSION: These data suggest that bortezomib was well tolerated and has significant single-agent activity in patients with certain subtypes of NHL.


Assuntos
Antineoplásicos/uso terapêutico , Ácidos Borônicos/uso terapêutico , Linfoma de Célula do Manto/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Inibidores de Proteases/uso terapêutico , Pirazinas/uso terapêutico , Adulto , Idoso , Ácidos Borônicos/efeitos adversos , Bortezomib , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pirazinas/efeitos adversos
3.
Br J Haematol ; 139(3): 425-8, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17910632

RESUMO

T-cell lymphomas (TCLs) are characterised by poor responses to therapy with brief durations of remissions. An early phase study of pralatrexate has demonstrated dramatic activity in patients with relapsed/refractory disease. Of the first 20 lymphoma patients treated, 16 had B-cell lymphoma and four had refractory aggressive TCL. All four patients with TCL achieved a complete remission. Patients with B-cell lymphoma achieved stable disease at best. For each TCL patient, the response was more durable than their best response with chemotherapy. This early experience is the first to document this unique activity of pralatrexate in TCL.


Assuntos
Aminopterina/análogos & derivados , Antineoplásicos/uso terapêutico , Antagonistas do Ácido Fólico/uso terapêutico , Linfoma de Células T/tratamento farmacológico , Adulto , Idoso , Aminopterina/metabolismo , Aminopterina/uso terapêutico , Antineoplásicos/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Antagonistas do Ácido Fólico/metabolismo , Humanos , Linfoma de Células B/tratamento farmacológico , Linfoma de Células T/diagnóstico por imagem , Masculino , Proteínas de Membrana Transportadoras/metabolismo , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Falha de Tratamento , Resultado do Tratamento
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