RESUMO
Objective. The aim of this study was to evaluate the efficacy and safety of a consecutive series of elderly patients with primary central nervous system lymphoma (PCNSL) treated with single-agent pemetrexed without radiotherapy or intrathecal chemotherapy. Methods. Twelve histologically confirmed newly diagnosed PCNSL patients older than 65 years were studied between 2008 and 2013. An induction chemotherapy was initially given (pemetrexed 600 mg/m2 on day 1, every 3 weeks). Patients achieving a complete, partial response or stable disease proceeded to a maintenance phase (up to 6 cycles). Patients with progressive/recurrent disease (PD) were treated with whole brain radiotherapy on an individual basis. Results. Four patients presented complete response, six patients showed partial response and two patients presented progressive disease. The median progression-free survival (PFS) was 9.0 months [95 % confidence interval (CI) 2.0-45.3] and the median overall survival was 19.5 months (95 % CI 5.0-45.3). Adverse events included leukocytopenia, anemia, fatigue, rash and vomiting. No neurotoxicity or treatment-related death was observed. The estimated 1-year and 2-year survival rate was 66.7 and 41.7 %, respectively. Conclusions. Our efficacy results demonstrate that the single-agent pemetrexed was feasible, active and well tolerated in elderly patients with PCNSL. Furthermore, this single-agent regimen results in higher response rates and less toxicity comparable with other chemotherapy or radiotherapy regimens. Prospectively, controlled studies are warranted to confirm such results (AU)
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Assuntos
Humanos , Masculino , Feminino , Idoso , Doenças do Sistema Nervoso Central/complicações , Doenças do Sistema Nervoso Central/patologia , Linfoma/congênito , Linfoma/metabolismo , Leucopenia/sangue , Fadiga/diagnóstico , Tomografia Computadorizada por Raios X/métodos , Estudos Retrospectivos , Doenças do Sistema Nervoso Central/diagnóstico , Doenças do Sistema Nervoso Central/metabolismo , Linfoma/complicações , Linfoma/diagnóstico , Intervalo Livre de Doença , Leucopenia/metabolismo , Fadiga/complicações , Tomografia Computadorizada por Raios XRESUMO
Dibenzo(a,l)pyrene (DBP) is among the most potent carcinogenic polycyclic aromatic hydrocarbons. Previously, we showed that DBP administration to pregnant mice resulted in high mortality of offspring from an aggressive T-cell lymphoma. All mice that survive to 10 months of age exhibit lung tumors with high multiplicity. Recombinant cytochrome P450 (cyp) 1b1 from mice and the homologue 1B1 in humans exhibit high activity toward the metabolic activation of DBP. Targeted disruption of the cyp1b1 gene protects against most DBP-dependent cancers. Mice heterozygous for the disrupted cyp1b1 allele were used to examine the effect of cyp1b1 gene dosage on DBP transplacental carcinogenesis. Dams were treated with 1 or 15 mg/kg of DBP or 50 mg/kg of benzo(a)pyrene. Cyp1b1-null offspring did not develop lymphoma, whereas wild-type and heterozygous siblings, born to dams given the high dose of DBP, exhibited significant mortalities between 10 and 30 weeks of age. At 10 months, all groups had lung adenomas or carcinomas [9.5%, 40.3%, 25.6%, and 100% incidences for controls, benzo(a)pyrene, 1 and 15 mg/kg DBP, respectively]. Cyp1b1 status did not alter benzo(a)pyrene-dependent carcinogenesis. At 1 mg/kg DBP, cyp1b1 status altered the incidence of lung tumors (19.0, 27.8, and 28.6% for nulls, heterozygous, and wild-type, respectively). At 15 mg/kg, tumor multiplicities in cyp1b1 wild-type (9.3) and heterozygous (9.5) offspring were nearly twice that of cyp1b1-null siblings (5.0). These data confirm that cyp1b1 bioactivation of DBP occurs in fetal target tissues, following transplacental exposure, with the thymus and lung as primary and secondary targets, respectively.
Assuntos
Hidrocarboneto de Aril Hidroxilases/genética , Benzopirenos/toxicidade , Feto/metabolismo , Exposição Materna/efeitos adversos , Troca Materno-Fetal , Neoplasias/induzido quimicamente , Animais , Hidrocarboneto de Aril Hidroxilases/metabolismo , Carcinógenos/toxicidade , Citocromo P-450 CYP1B1 , Feminino , Mortalidade Fetal , Feto/efeitos dos fármacos , Feto/enzimologia , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/congênito , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Linfoma/induzido quimicamente , Linfoma/congênito , Linfoma/genética , Linfoma/mortalidade , Troca Materno-Fetal/efeitos dos fármacos , Troca Materno-Fetal/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neoplasias/congênito , Neoplasias/genética , Neoplasias/mortalidade , Gravidez , Neoplasias do Timo/induzido quimicamente , Neoplasias do Timo/congênito , Neoplasias do Timo/genética , Neoplasias do Timo/mortalidadeAssuntos
Transformação Celular Neoplásica , Regressão Neoplásica Espontânea , Disgerminoma/congênito , Neoplasias Oculares/congênito , Feminino , Ganglioneuroma/patologia , Hormônios/fisiologia , Humanos , Sistema Imunitário/fisiologia , Lactente , Recém-Nascido , Infecções/fisiopatologia , Neoplasias Renais/congênito , Neoplasias Renais/patologia , Leucemia/congênito , Linfoma/congênito , Masculino , Neuroblastoma/congênito , Neuroblastoma/patologia , Oncogenes , Gravidez , Complicações Neoplásicas na Gravidez/patologia , Retinoblastoma/congênito , Teratoma/congênito , Neoplasias Testiculares/congênito , Tumor de Wilms/congênito , Tumor de Wilms/patologiaRESUMO
Lake Casitas wild mice were passively immunized as newborns with antiserum to congenitally transmitted murine leukemia virus. Immunization with immunoglobulin having a high neutralizing titer to ecotropic virus and a low titer to amphotropic virus correlated with the complete prevention of paralysis and a slight (25%), but statistically insignificant, reduction in the incidence of lymphoma. Occurrence of other tumor types and total mortality rate were not affected by immunization.
