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1.
N Engl J Med ; 366(19): 1770-81, 2012 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-22571201

RESUMO

BACKGROUND: Data are lacking on whether lenalidomide maintenance therapy prolongs the time to disease progression after autologous hematopoietic stem-cell transplantation in patients with multiple myeloma. METHODS: Between April 2005 and July 2009, we randomly assigned 460 patients who were younger than 71 years of age and had stable disease or a marginal, partial, or complete response 100 days after undergoing stem-cell transplantation to lenalidomide or placebo, which was administered until disease progression. The starting dose of lenalidomide was 10 mg per day (range, 5 to 15). RESULTS: The study-drug assignments were unblinded in 2009, when a planned interim analysis showed a significantly longer time to disease progression in the lenalidomide group. At unblinding, 20% of patients who received lenalidomide and 44% of patients who received placebo had progressive disease or had died (P<0.001); of the remaining 128 patients who received placebo and who did not have progressive disease, 86 crossed over to lenalidomide. At a median follow-up of 34 months, 86 of 231 patients who received lenalidomide (37%) and 132 of 229 patients who received placebo (58%) had disease progression or had died. The median time to progression was 46 months in the lenalidomide group and 27 months in the placebo group (P<0.001). A total of 35 patients who received lenalidomide (15%) and 53 patients who received placebo (23%) died (P=0.03). More grade 3 or 4 hematologic adverse events and grade 3 nonhematologic adverse events occurred in patients who received lenalidomide (P<0.001 for both comparisons). Second primary cancers occurred in 18 patients who received lenalidomide (8%) and 6 patients who received placebo (3%). CONCLUSIONS: Lenalidomide maintenance therapy, initiated at day 100 after hematopoietic stem-cell transplantation, was associated with more toxicity and second cancers but a significantly longer time to disease progression and significantly improved overall survival among patients with myeloma. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00114101.).


Assuntos
Antineoplásicos/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Transplante de Células-Tronco , Talidomida/análogos & derivados , Adulto , Idoso , Antineoplásicos/efeitos adversos , Intervalo Livre de Doença , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Lenalidomida , Quimioterapia de Manutenção , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/terapia , Segunda Neoplasia Primária/epidemiologia , Talidomida/efeitos adversos , Talidomida/uso terapêutico
2.
Br J Haematol ; 165(4): 497-503, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24528179

RESUMO

Aa total of 105 patients (age ≥18 years) with newly diagnosed low or intermediate risk acute promyelocytic leukaemia (APL) were treated with a standard induction and consolidation regimen including arsenic trioxide (ATO). Sixty-eight patients who were polymerase chain reaction (PCR) negative for PML-RARA post-consolidation were randomized to either 1 year of maintenance with tretinoin, mercaptopurine and methotrexate, or observation. Enrollment in this non-inferiority trial was stopped prematurely due to slow accrual. With a median follow up of 36·1 months, the overall survival of the 105 patients was 93%, and there have been no relapses in the patients randomized to maintenance or observation. These results demonstrate that cures can be expected in >90% of patients with low and intermediate risk APL and suggest that maintenance therapy may not be needed if patients are treated with an intensive post-remission regimen including ATO. This trial was registered at clinicaltrials.gov as #NCT00492856.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia de Consolidação , Leucemia Promielocítica Aguda/tratamento farmacológico , Adulto , Idoso , Aminoglicosídeos/administração & dosagem , Aminoglicosídeos/efeitos adversos , Animais , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Trióxido de Arsênio , Arsenicais/administração & dosagem , Arsenicais/efeitos adversos , Biomarcadores Tumorais , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Daunorrubicina/administração & dosagem , Daunorrubicina/efeitos adversos , Intervalo Livre de Doença , Cães , Feminino , Gemtuzumab , Humanos , Quimioterapia de Manutenção , Masculino , Mercaptopurina/administração & dosagem , Mercaptopurina/efeitos adversos , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Proteínas de Fusão Oncogênica/sangue , Óxidos/administração & dosagem , Óxidos/efeitos adversos , Contagem de Plaquetas , Indução de Remissão , Risco , Resultado do Tratamento , Tretinoína/administração & dosagem , Tretinoína/efeitos adversos , Adulto Jovem
3.
J Drugs Dermatol ; 9(8): 1017-8, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20684155

RESUMO

Topical 5-fluorouracil (5-FU) has been used in the treatment of various benign and malignant tumors of the skin, but only few address its therapeutic value on cutaneoues T-cell lymphoma. (CTCL). The authors report six cases of early stage CTCL responded to topical 5-FU. All of these patients (four females and two males) with early stage CTCL (1A = 4; 18 = 1; 2B = 1) had good response to topical 5-FU following three to 18 months' treatment. Four patients achieved complete response (CR) and two patients responded partially (PR). Tolerance to the treatment was good, with the exception of mild irritation, with no patients reporting serious side effects. The overall efficacy, relatively modest price and low incidence of side effects indicate that topical 5-FU has a place for treatment of early stage CTCL.


Assuntos
Fluoruracila/uso terapêutico , Linfoma Cutâneo de Células T/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Administração Cutânea , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/uso terapêutico , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Linfoma Cutâneo de Células T/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Cutâneas/patologia , Resultado do Tratamento
4.
Clin Cancer Res ; 20(20): 5255-64, 2014 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-25165100

RESUMO

PURPOSE: The lipoate derivative CPI-613 is a first-in-class agent that targets mitochondrial metabolism. This study determined the effects of CPI-613 on mitochondrial function and defined the MTD, pharmacokinetics, and safety in patients with relapsed or refractory hematologic malignancies. EXPERIMENTAL DESIGN: Human leukemia cell lines were exposed to CPI-613 and mitochondrial function was assayed. A phase I trial was conducted in which CPI-613 was given as a 2-hour infusion on days 1 and 4 for 3 weeks every 28 days. RESULTS: CPI-613 inhibited mitochondrial respiration of human leukemia cells consistent with the proposed mechanism of action. In the phase I trial, 26 patients were enrolled. CPI-613 was well tolerated with no marrow suppression observed. When the infusion time was shortened to 1 hour, renal failure occurred in 2 patients. At 3,780 mg/m(2), there were two dose-limiting toxicities (DLT). At a dose of 2,940 mg/m(2) over 2 hours, no DLTs were observed, establishing this as the MTD. Renal failure occurred in a total of 4 patients and resolved in all but 1, who chose hospice care. CPI-613 has a triphasic elimination with an alpha half-life of approximately 1.34 hours. Of the 21 evaluable, heavily pretreated patients, 4 achieved an objective response and 2 achieved prolonged stabilization of disease for a clinical benefit rate of 29%. Following drug exposure, gene expression profiles of peripheral blood mononuclear cells from responders demonstrated immune activation. CONCLUSION: CPI-613 inhibits mitochondrial function and demonstrates activity in a heavily pretreated cohort of patients.


Assuntos
Antineoplásicos/uso terapêutico , Caprilatos/uso terapêutico , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/patologia , Sulfetos/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/farmacologia , Caprilatos/farmacologia , Linhagem Celular Tumoral , Esquema de Medicação , Feminino , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/metabolismo , Neoplasias Hematológicas/mortalidade , Humanos , Leucemia/tratamento farmacológico , Leucemia/metabolismo , Leucemia/patologia , Masculino , Pessoa de Meia-Idade , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons , Sulfetos/farmacologia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto Jovem
5.
J Am Geriatr Soc ; 59(10): 1837-46, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22091497

RESUMO

OBJECTIVES: To test the feasibility and utility of a bedside geriatric assessment (GA) to detect impairment in multiple geriatric domains in older adults initiating chemotherapy for acute myelogenous leukemia (AML). DESIGN: Prospective observational cohort study. SETTING: Single academic institution. PARTICIPANTS: Individuals aged 60 and older with newly diagnosed AML and planned chemotherapy. MEASUREMENTS: Bedside GA was performed during inpatient exmination for AML. GA measures included the modified Mini-Mental State Examination; Center for Epidemiologic Studies Depression Scale; Distress Thermometer, Pepper Assessment Tool for Disability (includes self- reported activities of daily living (ADLs), instrumental ADLs, and mobility questions); Short Physical Performance Battery (includes timed 4-m walk, chair stands, standing balance); grip strength, and Hematopoietic Cell Transplantation Comorbidity Index. RESULTS: Of 54 participants (mean age 70.8 ± 6.4) eligible for this analysis, 92.6% completed the entire GA battery (mean time 44.0 ± 14 minutes). The following impairments were detected: cognitive impairment, 31.5%; depression, 38.9%; distress, 53.7%; impairment in ADLs, 48.2%; impaired physical performance, 53.7%; and comorbidity, 46.3%. Most were impaired in one (92.6%) or more (63%) functional domains. For the 38 participants rated as having good performance status according to standard oncologic assessment (Eastern Cooperative Oncology Performance Scale score ≤1), impairments in individual GA measures ranged from 23.7% to 50%. Significant variability in cognitive, emotional, and physical status was detected even after stratification according to tumor biology (cytogenetic risk group classification). CONCLUSION: Inpatient GA was feasible and added new information to standard oncology assessment, which may be important for stratifying therapeutic risk in older adults with AML.


Assuntos
Avaliação Geriátrica/métodos , Hospitalização , Leucemia Mieloide Aguda/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Comorbidade , Avaliação da Deficiência , Estudos de Viabilidade , Feminino , Humanos , Quimioterapia de Indução , Masculino , North Carolina , Avaliação em Enfermagem , Estudos Prospectivos
6.
Clin Lymphoma Myeloma Leuk ; 10(2): 129-33, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20371446

RESUMO

BACKGROUND: We report a retrospective study of 452 patients with lymphoma from 1991 to 2006, with 274 men and 178 women, median age of 50 years (range, 16-76 years). PATIENTS AND METHODS: There were 85 patients with Hodgkin lymphoma (HL) and 367 with non-Hodgkin lymphoma (NHL). Eleven patients received a second autologous transplantation for progressive lymphoma, and another 4 received a second allogeneic transplantation for myelodysplastic syndrome (MDS). Twenty-seven patients had skin biopsies, and 2 patients had gastrointestinal biopsies consistent with graft-versus-host disease (GVHD), and 11 patients developed severe engraftment syndrome (ES), as defined by noninfectious fever and skin rash with or without pulmonary infiltrates requiring systemic steroids. RESULTS: The median follow-up of the patients was 6.2 years, and median overall survival was 5.3 years. Twenty-four patients (5.3%) developed MDS with median time of onset of 4.2 years (range, 8 months to 7.5 years). An additional 5 patients developed clonal karyotypic abnormalities in the bone marrow without clinical MDS. Actuarial probabilities of developing MDS at 5 and 8 years after transplantation were 5% and 15%, respectively. CONCLUSION: The incidences of MDS are similar in HL and NHL. Multivariate analysis revealed older age, occurrence of ES/GVHD, and longer intervals between the initial diagnoses to transplantation as independent factors. It is conceivable that perturbation to the host immunity caused by either previous chemotherapy or conditioning regimens in the elderly might play a role in the development of MDS after autologous transplantation.


Assuntos
Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença de Hodgkin/terapia , Linfoma não Hodgkin/terapia , Síndromes Mielodisplásicas/etiologia , Síndromes Mielodisplásicas/terapia , Idoso , Terapia Biológica/efeitos adversos , Medula Óssea/patologia , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/mortalidade , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença de Hodgkin/complicações , Doença de Hodgkin/tratamento farmacológico , Humanos , Doenças do Sistema Imunitário/complicações , Doenças do Sistema Imunitário/tratamento farmacológico , Incidência , Linfoma/complicações , Linfoma/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/patologia , Masculino , Síndromes Mielodisplásicas/tratamento farmacológico , Estudos Retrospectivos , Transplante de Células-Tronco/efeitos adversos , Síndrome , Transplante Autólogo/efeitos adversos , Transplante Homólogo/efeitos adversos
7.
J Dermatolog Treat ; 20(3): 169-76, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19016373

RESUMO

BACKGROUND: Various combination therapies are used in refractory cutaneous T-cell lymphoma (CTCL). Although bexarotene has been studied in combination with psoralen photochemotherapy (PUVA), IFN-alpha and denileukin difitox, there have been no published data assessing the efficacy of the combination of bexarotene and methotrexate. OBJECTIVE: To evaluate the efficacy and safety of an oral bexarotene and methotrexate combination for the treatment of refractory CTCL. METHOD: A retrospective study was carried out of 12 patients with refractory stage CTCL treated with an oral combination of bexarotene and methotrexate from 2000 to 2007. RESULTS: Twelve patients with CTCL stage IA-IIB disease who received a combination of bexarotene and methotrexate were identified. The median dose of bexarotene was 150 mg/day (range 75-300 mg/day) and methotrexate 15 mg/week (range 5-30 mg/week). The duration of time to achieve an overall response was 6.5 months (range 3-11 months). The overall response occurred in 66% (8/12). One patient had complete response (CR = 8%) and seven had partial response (PR = 58%). Six of 12 patients progressed at some point during treatment and needed additional intervention. Tolerance to the treatment was good and commonly observed side effects were hyperlipidemia, elevated liver transaminases and a decreased white blood cell count. Limitations of the study included a restricted number of patients, relatively short evaluation times and retrospective analysis. CONCLUSION: An oral bexarotene and methotrexate combination may be a promising future alternative to monotherapy for the treatment of CTCL, but further studies are required.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linfoma Cutâneo de Células T/tratamento farmacológico , Linfoma Cutâneo de Células T/patologia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Administração Oral , Adulto , Fatores Etários , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bexaroteno , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Seguimentos , Humanos , Linfoma Cutâneo de Células T/mortalidade , Masculino , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Micose Fungoide/tratamento farmacológico , Micose Fungoide/mortalidade , Micose Fungoide/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Medição de Risco , Fatores Sexuais , Neoplasias Cutâneas/mortalidade , Taxa de Sobrevida , Tetra-Hidronaftalenos/administração & dosagem , Tetra-Hidronaftalenos/efeitos adversos , Resultado do Tratamento
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