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1.
PLoS One ; 15(9): e0238238, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32881880

RESUMO

The prognosis for patients with glioblastoma (GB) remains grim. Concurrent temozolomide (TMZ) radiation-the cornerstone of glioma control-extends the overall median survival of GB patients by only a few months over radiotherapy alone. While these survival gains could be partly attributed to radiosensitization, this benefit is greatly minimized in tumors expressing O6-methylguanine DNA methyltransferase (MGMT), which specifically reverses O6-methylguanine lesions. Theoretically, non-O6-methylguanine lesions (i.e., the N-methylpurine adducts), which represent up to 90% of TMZ-generated DNA adducts, could also contribute to radiosensitization. Unfortunately, at concentrations attainable in clinical practice, the alkylation capacity of TMZ cannot overwhelm the repair of N-methylpurine adducts to efficiently exploit these lesions. The current therapeutic application of TMZ therefore faces two main obstacles: (i) the stochastic presence of MGMT and (ii) a blunted radiosensitization potential at physiologic concentrations. To circumvent these limitations, we are developing a novel molecule called NEO212-a derivatization of TMZ generated by coupling TMZ to perillyl alcohol. Based on gas chromatography/mass spectrometry and high-performance liquid chromatography analyses, we determined that NEO212 had greater tumor cell uptake than TMZ. In mouse models, NEO212 was more efficient than TMZ at crossing the blood-brain barrier, preferentially accumulating in tumoral over normal brain tissue. Moreover, in vitro analyses with GB cell lines, including TMZ-resistant isogenic variants, revealed more potent cytotoxic and radiosensitizing activities for NEO212 at physiologic concentrations. Mechanistically, these advantages of NEO212 over TMZ could be attributed to its enhanced tumor uptake presumably leading to more extensive DNA alkylation at equivalent dosages which, ultimately, allows for N-methylpurine lesions to be better exploited for radiosensitization. This effect cannot be achieved with TMZ at clinically relevant concentrations and is independent of MGMT. Our findings establish NEO212 as a superior radiosensitizer and a potentially better alternative to TMZ for newly diagnosed GB patients, irrespective of their MGMT status.


Assuntos
Dacarbazina/análogos & derivados , Resistencia a Medicamentos Antineoplásicos , Glioma/tratamento farmacológico , Radiossensibilizantes/uso terapêutico , Temozolomida/uso terapêutico , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Dacarbazina/análise , Dacarbazina/metabolismo , Dacarbazina/farmacologia , Dacarbazina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Cromatografia Gasosa-Espectrometria de Massas , Glioma/patologia , Humanos , Camundongos , Camundongos Endogâmicos C57BL , O(6)-Metilguanina-DNA Metiltransferase/metabolismo , Radiossensibilizantes/análise , Radiossensibilizantes/metabolismo , Radiossensibilizantes/farmacologia , Temozolomida/análise , Temozolomida/metabolismo , Temozolomida/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
2.
Brasília; CONITEC; jul. 2020.
Não convencional em Português | BRISA/RedTESA | ID: biblio-1123192

RESUMO

INTRODUÇÃO: Embora não esteja entre os tumores malignos com maior incidência, o melanoma é considerado o tipo mais agressivo de câncer de pele devido ao grande potencial de disseminação à distância e consequente elevada letalidade. Em 2018, um total de 6.260 casos novos de melanoma maligno de pele foram estimados no Brasil, com aproximadamente 26% dos casos em estágio metastático e 1.794 óbitos registrados em 2015. O presente estudo avaliou as opções terapêuticas sistêmicas aprovadas pela Agência Nacional de Vigilância Sanitária (ANVISA) para o tratamento de primeira linha do melanoma avançado não cirúrgico e metastático. PERGUNTA: O uso de terapia-alvo ou imunoterapia é mais eficaz, seguro e custo-efetivo do que a quimioterapia com dacarbazina para o tratamento de primeira linha do melanoma avançado não-cirúrgico e metastático? TECNOLOGIAS: terapia-alvo (vemurafenibe, dabrafenibe, cobimetinibe, trametinibe) e imunoterapia (ipilimumabe, nivolumabe, pembrolizumabe). EVIDÊNCIAS CIENTÍFICAS: Quando comparadas ao tratamento padrão com dacarbazina, todas as terapias demonstraram superioridade estatisticamente significativa, tanto no desfecho de sobrevida livre de progressão (SLP) quanto em sobrevida global (SG), exceto dabrafenibe isolado. Em relação à SG, as estimativas pontuais demonstram maior benefício na redução do risco de morte com a combinação de nivolumabe/ipilimumabe (67%; 23% no pior cenário) seguida das imunoterapias isoladas com nivolumabe ou pembrolizumabe (54%; 41% no pior cenário), terapias-alvo combinadas (44-46%; 23-27% no pior cenário), imunoterapia isolada com ipilimumabe (32%; 7% no pior cenário) e terapia-alvo isolada com vemurafenibe (20%; 3% no pior cenário). Os eventos adversos graus 3/4 foram avaliados entre as classes terapêuticas de terapia-alvo, imunoterapia e quimioterapia. Os estudos reportaram menor risco de eventos adversos para a imunoterapia isolada anti-PD-1 (nivolumabe e pembrolizumabe) em relação à dacarbazina. As classes terapêuticas que apresentaram maior risco de eventos adversos foram: terapia-alvo isolada, terapia-alvo combinada, imunoterapia isolada com anti-CTLA-4 e imunoterapia combinada, todas com estimativa pontual de risco relativo acima de 1,40. AVALIAÇÃO ECONÔMICA: A avaliação de custo-efetividade demonstrou o ipilimumabe como a alternativa com menor razão de custo-efetividade incremental (ICER) em relação à dacarbazina. O nivolumabe e a sua associação com ipilimumabe tiveram melhores resultados em efetividade, porém com maior custo. Uma redução do preço do nivolumabe em 8 vezes tornaria seu ICER menor que 1 PIB per capita em relação à dacarbazina. A análise de sensibilidade probabilística revelou incertezas sobre a análise e o nivolumabe + ipilimumabe teve maior probabilidade que a dacarbazina de ser custo-efetivo em limiares próximos a R$322.000/QALY. AVALIAÇÃO DE IMPACTO ORÇAMENTÁRIO: O impacto orçamentário incremental em 5 anos variou de R$ 617.226.282,43 a R$ 2.880.924.401,13 para o ipilimumabe e sua associação com nivolumabe, respectivamente. As associações com terapia-alvo resultaram em impacto orçamentário menor que o nivolumabe, pois nessas estratégias apenas metade da população que tem a mutação BRAF seria tratada. O modelo buscou considerar além dos custos com os medicamentos, os custos diretos relacionados aos tratamentos. RECOMENDAÇÃO PRELIMINAR DA CONITEC: Os membros do Plenário da CONITEC presentes na 84ª reunião ordinária, no dia 05 de dezembro de 2019, definiram que o tema deve ser submetido à consulta pública com recomendação preliminar desfavorável à incorporação no SUS de terapia-alvo e da imunoterapia para o tratamento de primeira linha de pacientes com melanoma avançado não-cirúrgico e metastático. Apesar destas terapias apresentarem maior eficácia em relação à dacarbazina, o elevado custo do tratamento produziu uma relação de custo-efetividade e um impacto orçamentário incrementais que inviabilizam a sua incorporação. CONSULTA PÚBLICA: A Consulta Pública nº 85/2019, ocorreu entre os dias 02/01/2020 e 21/01/2020. Foram recebidas 2.300 contribuições, das quais 1.995 (mil novecentos e noventa e cinco) foram do formulário de experiência ou opinião e 305 (trezentos e cinco) do formulário técnico científico. Das contribuições de experiência ou opinião, 92% discordaram da recomendação preliminar e entre as contribuições técnico-científicas, 95% discordaram da recomendação preliminar e a maior parte das contribuições foram relacionadas à eficácia da terapia-alvo e da imunoterapia quando comparadas à dacarbazina. Os principais argumentos foram relacionados ao direito ao acesso ao tratamento de alto custo, eficácia dos tratamentos avaliados, e obsolescência do medicamento mais amplamente utilizado atualmente do SUS (dacarbazina). Foram recebidas contribuições de 4 (quatro) empresas fabricantes das tecnologias. Algumas contribuições levaram à atualização do modelo econômico, mas mostraram que o nivolumabe e a combinação nivolumabe com ipilimumabe permaneceram sendo as estratégias não dominadas. Outras terapias passaram a ter dominância extendida, mas não passaram a ser dominantes. Na discussão do tema, os membros do Plenário destacaram que a utilização do desfecho "cura dos pacientes com melanoma metastático", conforme apresentado pelo fabricante, não é adequado, por se tratar de uma avaliação indireta por meio de dados da literatura sobre respostas completas sustentadas em um período determinado de tempo. Foi ressaltado, em termos gerais, que as terapias avaliadas, principalmente imunoterapias anti-PD1, mudam inteiramente o contexto atual do melanoma metastático, representando uma evolução no tratamento. Porém, o custo das terapias permanece muito elevado. Houve novas propostas de preços pelas empresas fabricantes dos medicamentos anti-PD1 avaliados (nivolumabe e pembrolizumabe) que apresentaram satisfatórios perfis de eficácia e segurança. Com as informações adicionais a avaliação econômica foi atualizada com a alteração da duração de tratamento do pembrolizumabe e com novos preços propostos pelas empresas. Para o nivolumabe houve a proposta de redução do preço que era de R$27.882,36 para R$20.939,69, com duração de tratamento até a progressão da doença ou morte. Para o pembrolizumabe houve a proposta de redução do preço que era de R$28.954,80 para R$23.724 (ICMS 17%) ou R$19.690,02 (ICMS 0%), com duração de tratamento até progressão da doença ou morte ou até vinte e quatro meses em pacientes sem progressão. RECOMENDAÇÃO FINAL: Os membros da Conitec presentes na 88ª reunião ordinária, no dia 08 de julho de 2020, deliberaram, por unanimidade, por recomendar a incorporação no Sistema Único de Saúde da classe anti-PD1 (nivolumabe ou pembrolizumabe), para tratamento de primeira linha do melanoma avançado não cirúrgico e metastático, conforme modelo da assistência oncológica no SUS. Foram levadas em consideração as novas propostas de preços apresentadas pelas empresas fabricantes dos medicamentos anti-PD1 avaliados (nivolumabe e pembrolizumabe) além dos satisfatórios perfis de eficácia e segurança demonstrado pelos dois medicamentos. Discutiu-se que o custo mensal do tratamento de ambos os medicamentos deveriam ainda ser reduzidos conforme valor de referência de 3 PIB/per capita para uma razão de custo-efetividade incremental favorável. Foi discutida também a possibilidade de criação de um valor máximo para o procedimento na tabela SIGTAP com a recomendação da classe terapêutica. Foi assinado o Registro de Deliberação nº 533/2020. DECISÃO: incorporar a classe anti-PD1 (nivolumabe e pembrolizumabe) para o tratamento de primeira linha do melanoma avançado não-cirúrgico e metastático, conforme o modelo da assistência oncológica, no âmbito do Sistema Único de Saúde - SUS, conforme a Portaria nº 23, publicada no Diário Oficial da União nº 149, seção 1, página 91, em 05 de agosto de 2020.


Assuntos
Humanos , Neoplasias Cutâneas/tratamento farmacológico , Dacarbazina/uso terapêutico , Ipilimumab/uso terapêutico , Vemurafenib/uso terapêutico , Nivolumabe/uso terapêutico , Melanoma/tratamento farmacológico , Metástase Neoplásica , Avaliação da Tecnologia Biomédica , Sistema Único de Saúde , Brasil , Análise Custo-Benefício/economia
3.
Ann Hematol ; 99(7): 1575-1581, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32500223

RESUMO

This study investigated the clinical characteristics of Hodgkin lymphoma-associated hemophagocytic lymphohistiocytosis (HLH-HL). Clinical data of 8 patients with HLH-HL and 20 non-HLH-HL patients were included. All eight HLH-HL patients tested positive for plasma Epstein-Barr virus (EBV)-DNA and EBV-encoded small RNA (EBER), and six patients were positive for EBV-DNA in the peripheral blood mononuclear cells (PBMCs). Two out of the 20 non-HLH-HL patients were confirmed positive for EBER, and the remaining 18 patients were negative. Among the HLH-HL patients, five patients received ABVD (doxorubicin/bleomycin/vinblastine/dacarbazine) chemotherapy regimens in other hospitals, and their conditions were considered to be worse, for which reason they were transferred to our center, and three patients were treated with DEP (doxorubicin-etoposide-methylprednisolone) regimens to target HLH and were alive as of the writing of this article. Two patients were critically ill upon admission and were not able to undergo chemotherapy. Significant differences in survival time were observed between the HLH-HL and non-HLH-HL patients (P = 0.005). HL patients found positive for EBV (plasma/PBMCs EBV-DNA(+)/EBER(+)) may be more likely to develop HLH-HL. It may be beneficial to target HLH during the acute phase of HLH, followed by treating HL once the HLH condition has stabilized. HLH-HL patients have worse prognosis and higher mortality than non-HLH-HL patients.


Assuntos
Doença de Hodgkin/mortalidade , Doença de Hodgkin/terapia , Linfo-Histiocitose Hemofagocítica/mortalidade , Linfo-Histiocitose Hemofagocítica/terapia , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/uso terapêutico , Estudos de Casos e Controles , Dacarbazina/uso terapêutico , Doxorrubicina/uso terapêutico , Infecções por Vírus Epstein-Barr/sangue , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/mortalidade , Infecções por Vírus Epstein-Barr/terapia , Etoposídeo/uso terapêutico , Feminino , Herpesvirus Humano 4/isolamento & purificação , Doença de Hodgkin/sangue , Doença de Hodgkin/complicações , Humanos , Linfo-Histiocitose Hemofagocítica/sangue , Linfo-Histiocitose Hemofagocítica/complicações , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Vimblastina/uso terapêutico , Adulto Jovem
6.
Hematol Oncol ; 38(2): 153-161, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31953864

RESUMO

The clinical management of older adult patients with Hodgkin lymphoma (HL) remains a major challenge. The aim of this study was to evaluate the impact of comorbidity assessment according to a standardized approach, the Cumulative Illness Rating Scale (CIRS), on prognosis in patients with classical HL aged 60 years and older. We studied 76 consecutive older adult patients with HL (median age 69 y, range 60-84) who had been treated in our institution between 1999 and 2018. Comorbidity was assessed at diagnosis according to CIRS. Anthracycline-containing chemotherapy with curative intent was administered in 59 (78%) patients. We identified 41 (54%) patients with at least one severe comorbidity rated on CIRS grade ≥ 3. Patients with severe comorbidity were more likely to have advanced-stage disease (P = .003), to have an International Prognostic Score (IPS) > 3 (P = .03), and to not receive anthracycline-containing chemotherapy (P = .008). The probability of overall survival (OS) at 3 years was 88% (95% CI, 71%-95%) in patients without severe comorbidities, while it was only 46% (95% CI, 29%-62%) in patients with a comorbidity CIRS grade ≥ 3 (P = .0001). The impact of comorbidity on prognosis was also evident when restricting the analysis to patients treated with anthracycline-containing therapy. The 3-year OS was 93% (95% CI, 76%-98%) (P = .004) in patients without severe comorbidity and 72% (95% CI, 47%-87%) in patients with severe comorbidity (P = .004). In a multivariate analysis, presence of comorbidity, but not age, was a significant factor for OS. Therefore, we conclude that a significant proportion of older adult patients with HL has severe comorbidity on the CIRS scale, which impacts more importantly than age on prognosis.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/epidemiologia , Doença de Hodgkin/patologia , Idoso , Idoso de 80 Anos ou mais , Bleomicina/uso terapêutico , Comorbidade , Dacarbazina/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Seguimentos , Doença de Hodgkin/tratamento farmacológico , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida , Vimblastina/uso terapêutico
7.
Blood ; 135(10): 735-742, 2020 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-31945149

RESUMO

The phase 3 ECHELON-1 study demonstrated that brentuximab vedotin (A) with doxorubicin, vinblastine, and dacarbazine (AVD; A+AVD) exhibited superior modified progression-free survival (PFS) vs doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) for frontline treatment of patients with stage III/IV classical Hodgkin lymphoma (cHL). Maturing positron emission tomography (PET)-adapted trial data highlight potential limitations of PET-adapted approaches, including toxicities with dose intensification and higher-than-expected relapse rates in PET scan after cycle 2 (PET2)-negative (PET2-) patients. We present an update of the ECHELON-1 study, including an exploratory analysis of 3-year PFS per investigator. A total of 1334 patients with stage III or IV cHL were randomized 1:1 to receive 6 cycles of A+AVD (n = 664) or ABVD (n = 670). Interim PET2 was required. At median follow-up of 37 months, 3-year PFS rates were 83.1% with A+AVD and 76.0% with ABVD; 3-year PFS rates in PET2- patients aged <60 years were 87.2% vs 81.0%, respectively. A beneficial trend in PET2+ patients aged <60 years on A+AVD was also observed, with a 3-year PFS rate of 69.2% vs 54.7% with ABVD. The benefit of A+AVD in the intent-to-treat population appeared independent of disease stage and prognostic risk factors. Upon continued follow-up, 78% of patients with peripheral neuropathy on A+AVD had either complete resolution or improvement compared with 83% on ABVD. These data highlight that A+AVD provides a durable efficacy benefit compared with ABVD for frontline stage III/IV cHL, consistent across key subgroups regardless of patient status at PET2, without need for treatment intensification or bleomycin exposure. This trial was registered at www.clinicaltrials.gov as #NCT01712490 (EudraCT no. 2011-005450-60).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Brentuximab Vedotin/administração & dosagem , Doença de Hodgkin/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Bleomicina/uso terapêutico , Brentuximab Vedotin/efeitos adversos , Dacarbazina/administração & dosagem , Dacarbazina/efeitos adversos , Dacarbazina/uso terapêutico , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Feminino , Seguimentos , Doença de Hodgkin/mortalidade , Doença de Hodgkin/patologia , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Análise de Sobrevida , Resultado do Tratamento , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , Vimblastina/uso terapêutico
8.
Curr Radiopharm ; 13(1): 56-62, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31749442

RESUMO

BACKGROUND: Malignant melanoma frequently spreads to the gastrointestinal tract, with 60% of patients with advanced metastatic disease showing digestive involvement; however, primary MM of the small intestine is a controversial diagnosis. In fact, whether these lesions arise as true small bowel primary neoplasms or represent metastases from unidentified cutaneous melanomas remains debatable. The most common complications are intestinal obstruction, massive gastrointestinal bleeding, and perforation. OBJECTIVE & METHODS: We report a case of a 64-year-old patient, with an unremarkable medical history, in which a late diagnosis of primary ileal malignant melanoma in the setting of an emergency laparotomy due to small bowel obstruction, and where PET-scan showed costal metastasis. Therefore, we provide a narrative review of the scientific literature about this topic. RESULTS: 36 cases of primary small bowel melanoma, included that in the present study, were found through our search in the scientific literature. CONCLUSION: Primary small bowel MM appears to be an extremely rare entity which clinicians should be more aware of, in order to plan better a correct strategy of early diagnosis and appropriate treatment.


Assuntos
Neoplasias do Íleo , Obstrução Intestinal , Melanoma , Antineoplásicos Alquilantes/uso terapêutico , Dacarbazina/uso terapêutico , Humanos , Neoplasias do Íleo/diagnóstico por imagem , Neoplasias do Íleo/tratamento farmacológico , Neoplasias do Íleo/patologia , Íleo/patologia , Obstrução Intestinal/diagnóstico por imagem , Obstrução Intestinal/tratamento farmacológico , Obstrução Intestinal/patologia , Masculino , Melanoma/diagnóstico por imagem , Melanoma/tratamento farmacológico , Melanoma/patologia , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons
9.
Neoplasma ; 67(1): 203-208, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31829022

RESUMO

Few studies focused on the relationship between hepatitis B virus (HBV) infection and classical Hodgkin lymphoma (cHL). This study was to evaluate the impact of HBV infection on the treatment outcome and survival of cHL patients. Clinical data of 352 cHL patients treated with ABVD regimen (doxorubicin, bleomycin, vincristine and dacarbazine) between January 2002 and January 2018 were retrospectively collected. According to HBV infection status, the patients were divided into three groups: with HBV infection [hepatitis B surface antigen (HBsAg)-positive], with past HBV infection [HBsAg-negative but anti-hepatitis B core antigen (anti-HBc)-positive], and without HBV infection (HBsAg-negative and anti-HBc-negative). The incidence of HBV infection and past HBV infection in cHL patients were 7.4% (26/352) and 16.5% (58/352), respectively. The median age of patients without HBV infection was lower than those in other two groups (p<0.001). The complete remission rates after first-line therapy were different among 3 groups (65.4% for the group with HBV infection, 87.9% for the group with past HBV infection, and 76.1% for the group without HBV infection, respectively, p=0.049). After a median follow-up of 34.6 months, the 3-year progression-free survival rates for the three groups were 69%, 74% and 80%, respectively (p=0.566) and the 3-year overall survival rates were 72%, 91% and 87%, respectively (p=0.096). No HBV reactivation was observed during chemotherapy among 3 groups, but 1 patient in the group with HBV infection experienced delayed HBV reactivation when prophylactic entecavir was discontinued 12 months after the last cycle of chemotherapy. HBV infection status did not affect the clinical outcome and prognosis of cHL patients, especially in the era of prophylactic antiviral therapy.


Assuntos
Hepatite B/complicações , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/virologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/uso terapêutico , Dacarbazina/uso terapêutico , Doxorrubicina/uso terapêutico , Antígenos do Núcleo do Vírus da Hepatite B , Antígenos de Superfície da Hepatite B , Humanos , Prognóstico , Estudos Retrospectivos , Vimblastina/uso terapêutico
10.
BMJ Case Rep ; 12(12)2019 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-31818889

RESUMO

A 63-year-old man presented to the hospital with generalised weakness, fatigue and a 22 kg weight loss 4 months after being diagnosed with sarcoidosis on a mediastinal lymph node biopsy, with minimal improvement in symptoms on prednisone and methotrexate therapy. On arrival, he was found to have a haemoglobin of 57 g/L and platelet count of 82×109/L. Further work-up revealed six of eight diagnostic criteria for haemophagocytic lymphohistiocytosis (HLH): fever >38.9°C, splenomegaly, cytopaenia, hypertriglyceridaemia, haemophagocytosis and elevated ferritin >31 000 ng/mL. He was also found to have Epstein-Barr viraemia with greater than 17 000 copies. Bone marrow biopsy showed the presence of haemophagocytic histiocytes and evidence of classic Hodgkin's lymphoma. He was started on HLH-94 protocol. Later treatment was switched to lymphoma-directed therapy and he finished six cycles of A+AVD (brentuximab vedotin, doxorubicin, vinblastine and dacarbazine) with end-of-treatment positron emission tomography/CT and bone marrow negative for lymphoma.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/complicações , Doença de Hodgkin/tratamento farmacológico , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Linfo-Histiocitose Hemofagocítica/etiologia , Dacarbazina/uso terapêutico , Doxorrubicina/uso terapêutico , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/diagnóstico , Doença de Hodgkin/diagnóstico , Humanos , Linfo-Histiocitose Hemofagocítica/diagnóstico , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Vimblastina/uso terapêutico , Viremia/complicações , Viremia/diagnóstico
11.
J Glob Oncol ; 5: 1-13, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31834832

RESUMO

PURPOSE: Escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) improves overall survival (OS) in patients with Hodgkin lymphoma (HL) relative to ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) therapy. However, the associated higher cost and toxicity discourage clinicians from prescribing it. Identifying high-risk patients and administering escalated BEACOPP remains an effective strategy. We assessed the significance of interim positron emission tomography (iPET) scan after 2 cycles (iPET2) in identifying this high-risk subset. PATIENTS AND METHODS: This cohort study used secondary data from 12 tertiary care centers in South India gathered over 10 years (2008-2018). OS, event-free survival (EFS), determinants of EFS, and complete response (CR) in iPET2 were assessed. RESULTS: The study included 409 patients with HL (mean age, 34.5 years; male/female ratio, 1.4:1). The median duration of follow-up was 2.8 years. Of 409 patients, 63% underwent PET-based staging and 37% underwent computerized tomography (CT) staging. Stage IV (28.9%) and bone involvement (9.2%) were seen more often with PET than with CT staging (9.2% and 2%, respectively). Among 171 patients with iPET2 results, 24% did not achieve CR, and no factors were significantly associated. The 5-year EFS and OS rates of the entire cohort were 78% and 97%, respectively. The 5-year EFS and OS rates of patients with CR on iPET2 were 90% and 99%, respectively, whereas these were 65% and 100%, respectively, for patients not achieving CR. On univariable analysis, sex, stage, and iPET2 response significantly predicted inferior EFS. On multivariate analysis, only iPET2 response significantly predicted EFS (P < .000). CONCLUSION: Our study supports the use of PET for staging and iPET2 for response assessment. Nonachievement of CR on iPET2 indicates unfavorable outcome, and such patients may benefit from more intensive treatment.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/tratamento farmacológico , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bleomicina/efeitos adversos , Bleomicina/uso terapêutico , Criança , Pré-Escolar , Dacarbazina/efeitos adversos , Dacarbazina/uso terapêutico , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Feminino , Doença de Hodgkin/mortalidade , Doença de Hodgkin/patologia , Humanos , Índia , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Análise de Sobrevida , Resultado do Tratamento , Vimblastina/efeitos adversos , Vimblastina/uso terapêutico , Adulto Jovem
12.
Eur J Cancer ; 123: 58-71, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31670077

RESUMO

BACKGROUND: Although a myriad of novel treatments entered the treatment paradigm for advanced melanoma, there is lack of head-to-head evidence. We conducted a network meta-analysis (NMA) to estimate each treatment's relative effectiveness and safety. METHODS: A systematic literature review (SLR) was conducted in Embase, MEDLINE and Cochrane to identify all phase III randomised controlled trials (RCTs) with a time frame from January 1, 2010 to March 11, 2019. We retrieved evidence on treatment-related grade III/IV adverse events, progression-free survival (PFS) and overall survival (OS). Evidence was synthesised using a Bayesian fixed-effect NMA. Reference treatment was dacarbazine. In accordance with RCTs, dacarbazine was pooled with temozolomide, paclitaxel and paclitaxel plus carboplatin. To increase homogeneity of the study populations, RCTs were only included if patients were not previously treated with novel treatments. RESULTS: The SLR identified 28 phase III RCTs involving 14,376 patients. Nineteen and seventeen treatments were included in the effectiveness and safety NMA, respectively. For PFS, dabrafenib plus trametinib (hazard ratio [HR] PFS: 0.21) and vemurafenib plus cobimetinib (HR PFS: 0.22) were identified as most favourable treatments. Both had, however, less favourable safety profiles. Five other treatments closely followed (dabrafenib [HR PFS: 0.30], nivolumab plus ipilimumab [HR PFS: 0.34], vemurafenib [HR PFS: 0.38], nivolumab [HR PFS: 0.42] and pembrolizumab [HR PFS: 0.46]). In contrast, for OS, nivolumab plus ipilimumab (HR OS: 0.39), nivolumab (HR OS: 0.46) and pembrolizumab (HR OS: 0.50) were more favourable than dabrafenib plus trametinib (HR OS: 0.55) and vemurafenib plus cobimetinib (HR OS: 0.57). CONCLUSIONS: Our NMA identified the most effective treatment options for advanced melanoma and provided valuable insights into each novel treatment's relative effectiveness and safety. This information may facilitate evidence-based decision-making and may support the optimisation of treatment and outcomes in everyday clinical practice.


Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Vacinas Anticâncer/uso terapêutico , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Azetidinas/administração & dosagem , Azetidinas/uso terapêutico , Benzimidazóis/administração & dosagem , Benzimidazóis/uso terapêutico , Carboplatina/administração & dosagem , Carboplatina/uso terapêutico , Dacarbazina/administração & dosagem , Dacarbazina/uso terapêutico , Humanos , Hidrazinas/administração & dosagem , Hidrazinas/uso terapêutico , Imidazóis/administração & dosagem , Imidazóis/uso terapêutico , Interleucina-2/administração & dosagem , Interleucina-2/uso terapêutico , Ipilimumab/administração & dosagem , Ipilimumab/uso terapêutico , Lenalidomida/administração & dosagem , Lenalidomida/uso terapêutico , Melanoma/imunologia , Melanoma/patologia , Metanálise em Rede , Compostos de Nitrosoureia/administração & dosagem , Compostos de Nitrosoureia/uso terapêutico , Nivolumabe/administração & dosagem , Nivolumabe/uso terapêutico , Compostos Organofosforados/administração & dosagem , Compostos Organofosforados/uso terapêutico , Oximas/administração & dosagem , Oximas/uso terapêutico , Paclitaxel/administração & dosagem , Paclitaxel/uso terapêutico , Piperidinas/administração & dosagem , Piperidinas/uso terapêutico , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Piridonas/administração & dosagem , Piridonas/uso terapêutico , Pirimidinonas/administração & dosagem , Pirimidinonas/uso terapêutico , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Sorafenibe/administração & dosagem , Sorafenibe/uso terapêutico , Taxa de Sobrevida , Temozolomida/administração & dosagem , Temozolomida/uso terapêutico , Resultado do Tratamento
13.
J Pak Med Assoc ; 69(9): 1266-1272, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31511710

RESUMO

Purpose: Hodgkin lymphoma (HL) is one of the most curable paediatric cancers, with long-term survival rates now exceeding 90% after treatment with chemotherapy alone or combined with radiotherapy (RT). Treatment options for Hodgkin's Lymphoma differ among various study groups and there is still no consensus regarding the standard treatment for Hodgkin's lymphoma. Taking into account the impact of treatment-related mortality in low- and middle-income countries we propose to study the the clinical features and treatment outcomes by using different chemotherapy protocols in Hodgk in s' s Lymphoma children's at Shaukat khanam hospital Lahore.. METHODS: Clinical data from a large regional cancer center Pediatrics patients with Hodgkin's Lymphoma from January 2009 till December 2015 was retrospectively collected after Institutional Review Board (IRB) approval. RESULTS: A total of 748 patients were reviewed retrospectively. Mostly (45%) were in 6-10 years age group. Male showed predominance ,male to female ratio was 4:1. B symptoms were present in 51%, bulky disease in 44% and ESR was more than 30mm in 26% of patients. CD 30 was positive in 95%, Bone marrow involved in 13% of patients. Stage I in 8%, stage- II in 27%, stage -III in 39% and stage IV in 26% was seen. COPDAc/ABVD was given in 412 patients, CHLVPP/ABVD in 176 patients, OEPA/COPP in 57 patients, OEPA in 35 patients, OEPA/COPDAC in 33 Patients and remaining 33 received various chemotherapy protocol combination. XRT was given in 17% of patients. Of these 86% of patients were alive ,5% patients died , 3% patients abandoned, 6% patients relapsed ,3% patients progressed while on chemotherapy. Five years Overall survival was 94% and 5 Years Event free survival was 91%. Minimum haematological and other toxicity was seen in patients who had received COPDac/ABVD when compared to other regimen. CONCLUSIONS: Hodgkin's lymphoma patients had good outcome with different chemotherapy regimens, however our experience showed that the COPDac/ABVD regimen wass better tolerated with minimum toxicity.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Adolescente , Bleomicina/uso terapêutico , Criança , Pré-Escolar , Clorambucila/uso terapêutico , Ciclofosfamida/uso terapêutico , Dacarbazina/uso terapêutico , Doxorrubicina/uso terapêutico , Etoposídeo/uso terapêutico , Feminino , Doença de Hodgkin/patologia , Humanos , Lactente , Estimativa de Kaplan-Meier , Masculino , Estadiamento de Neoplasias , Paquistão , Prednisolona/uso terapêutico , Prednisona/uso terapêutico , Procarbazina/uso terapêutico , Prognóstico , Radioterapia Adjuvante , Estudos Retrospectivos , Taxa de Sobrevida , Centros de Atenção Terciária , Resultado do Tratamento , Vimblastina/uso terapêutico , Vincristina/uso terapêutico
14.
Cancer Immunol Immunother ; 68(9): 1547-1559, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31482307

RESUMO

Engineered cytokine products represent promising agents for the treatment of immunogenic tumors, such as malignant melanoma, in addition to immune checkpoint inhibitors. Here we describe the results of a controlled, randomized phase II clinical trial, aimed at assessing the therapeutic potential of L19IL2, a fully human fusion protein consisting of the L19 antibody specific to the alternatively spliced extra-domain B of fibronectin, fused to human interleukin-2 in advanced metastatic melanoma. In one arm, patients received dacarbazine (DTIC; 1000 mg/m2 of body surface on day 1 of 21-day cycles) as single agent, while in two other arms L19IL2 (22.5 million international units of IL2 equivalents) was added, based on two different schedules of administration. In total, 69 patients with stage IV melanoma were enrolled (24 in the dacarbazine arm, 23 and 22 in the other combination arms, respectively) and 67 received treatment. Analyses of efficacy results show a statistically significant benefit in terms of overall response rate and median progression-free survival for patients receiving L19IL2 in combination with DTIC, compared to DTIC as single agent. In light of these results, further clinical investigations with L19IL2 (alone or in combination with other agents) are warranted.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Dacarbazina/uso terapêutico , Melanoma/terapia , Proteínas Recombinantes de Fusão/uso terapêutico , Neoplasias Cutâneas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Melanoma/mortalidade , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Cutâneas/mortalidade , Análise de Sobrevida , Adulto Jovem
15.
Expert Rev Hematol ; 12(10): 801-808, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31432732

RESUMO

Introduction: Outcomes of patients with classical Hodgkin lymphoma are excellent, and the intent of frontline therapy for even advanced-stage disease has been curative. This review summarizes the role of brentuximab vedotin in the upfront treatment of advanced stage classical Hodgkin lymphoma in the context of reducing therapy-related toxicity without compromising the high cure rate. Areas covered: Strategies to reduce bleomycin-induced lung toxicity include a response-adapted approach investigated in the RATHL study and a replacement of bleomycin with brentuximab vedotin in frontline chemotherapy regimens. In both studies, omission of bleomycin in the non-standard arms decreased the rate of pulmonary toxicity while maintaining high progression-free survival and overall survival rates. Expert opinion: The approval of A+AVD in North America offers a new bleomycin-free regimen for the treatment of advanced-stage HL, but it must be balanced against a risk-adapted approach. Recently presented subset analyses raise a question about which patients benefit most from this therapy.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bleomicina/administração & dosagem , Brentuximab Vedotin/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Imunotoxinas/uso terapêutico , Antineoplásicos Imunológicos/economia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bleomicina/efeitos adversos , Bleomicina/economia , Brentuximab Vedotin/economia , Ensaios Clínicos como Assunto , Análise Custo-Benefício , Dacarbazina/economia , Dacarbazina/uso terapêutico , Doxorrubicina/economia , Doxorrubicina/uso terapêutico , Feminino , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/economia , Doença de Hodgkin/mortalidade , Humanos , Imunotoxinas/economia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Guias de Prática Clínica como Assunto , Análise de Sobrevida , Vimblastina/economia , Vimblastina/uso terapêutico
16.
Am J Health Syst Pharm ; 76(6): 381-386, 2019 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-31361838

RESUMO

PURPOSE: A novel value-based approach to evaluate costly specialty drugs for formulary addition was developed. SUMMARY: In February 2016, Stanford Health Care launched the specialty drug subcommittee (SDSC), a subcommittee of the pharmacy and therapeutics committee, responsible for the formulary review of specialty pharmaceuticals. A process was developed for value-based review that includes not only consideration of clinical trial data and institutional acquisition costs but also internal patient outcomes and a cost-effectiveness model using internal financial data. A Markov model was developed to assess the value of trabectedin, which was approved for formulary addition in April 2016, relative to the addition of dacarbazine. The economic model and internal patient outcome analysis were presented to the prescribing oncologist and the SDSC for review. Internal data revealed that fewer patients than had been estimated received trabectedin, with outcomes significantly worse than those observed in the clinical trial leading to Food and Drug Administration approval. In the cost-effectiveness model, trabectedin had higher costs and poorer outcomes compared with dacarbazine. Based on the economic model, low utilization, and real-world outcomes, trabectedin was removed from formulary and a restrictive treatment pathway for nonformulary use, developed by the primary prescriber, was implemented. This process has since been applied to 11 more specialty drugs. CONCLUSION: Internal cost-effectiveness models in combination with real-world patient outcomes data can be effective formulary management tools. Engagement and collaboration with the requesting provider are key to developing thoughtful treatment pathways.


Assuntos
Análise Custo-Benefício , Farmacoeconomia , Formulários Farmacêuticos como Assunto , Assistência Farmacêutica/organização & administração , Comitê de Farmácia e Terapêutica/organização & administração , Centros Médicos Acadêmicos/organização & administração , Ensaios Clínicos como Assunto , Dacarbazina/economia , Dacarbazina/uso terapêutico , Aprovação de Drogas/economia , Custos de Medicamentos , Revisão de Uso de Medicamentos/métodos , Revisão de Uso de Medicamentos/organização & administração , Humanos , Comunicação Interdisciplinar , Cadeias de Markov , Modelos Econômicos , Neoplasias/tratamento farmacológico , Neoplasias/economia , Trabectedina/economia , Trabectedina/uso terapêutico , Resultado do Tratamento , Estados Unidos , United States Food and Drug Administration
17.
Rev Med Chil ; 147(4): 437-443, 2019 Apr.
Artigo em Espanhol | MEDLINE | ID: mdl-31344204

RESUMO

BACKGROUND: Hodgkin lymphoma has a high rate of curability, even in advanced stages. AIM: To assess the results of Hodgkin lymphoma treatment using the ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) chemotherapy regimen. MATERIAL AND METHODS: Analysis of a database held by the Chilean Ministry of Health, including all patients treated at accredited cancer treatment centers. RESULTS: Data for 915 patients, median age 35 years (range 15-86 years) and followed for a median of 97 months (range 1-347 months) were analyzed. Forty-one percent had localized disease. Overall survival at five years for localized and advanced stages was 92% and 74%, respectively. The figures for progression free survival were 87% and 64%, respectively. Patients with relapse who received autologous stem cell transplantation (ASCT) had a five year overall survival of 92%, compared to 64% among those who did not undergo this procedure (p < 0.01). The Guarantees in Health Program set up by the Ministry of Health, was associated with earlier stage disease at diagnosis. CONCLUSIONS: The ABVD regimen achieves high rates of cure in localized stages of the disease but the results in advanced stages are not optimal. ASCT significantly improves survival in patients with relapse. The Guarantees in Health Program is associated with earlier diagnosis of the disease.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bleomicina/uso terapêutico , Chile , Dacarbazina/uso terapêutico , Intervalo Livre de Doença , Doxorrubicina/uso terapêutico , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Doença de Hodgkin/mortalidade , Doença de Hodgkin/patologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento , Vimblastina/uso terapêutico , Adulto Jovem
18.
Blood ; 134(15): 1238-1246, 2019 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-31331918

RESUMO

Patients with advanced-stage Hodgkin lymphoma (HL) demonstrated excellent 2-year progression-free survival (PFS) after receiving positron emission tomography (PET)-adapted therapy on SWOG S0816. Patients received 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). Patients achieving complete response (CR) on PET scan following cycle 2 of ABVD (PET2) continued 4 additional cycles of ABVD. Patients not achieving CR on PET2 were switched to escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (eBEACOPP) for 6 cycles. After a median follow-up of 5.9 years, a subset of 331 eligible patients with central review of PET2 was analyzed. PET2 was negative in 82% and positive in 18%. For all patients, the estimated 5-year PFS and OS was 74% (95% confidence interval [CI], 69%-79%) and 94% (95% CI, 91%-96%), respectively. For PET2- and PET2+ patients, the 5-year PFS was 76% (95% CI, 70%-81%) and 66% (95% CI, 52%-76%), respectively. Seven (14%) and 6 (2%) patients reported second cancers after treatment with eBEACOPP and ABVD, respectively (P = .001). Long-term OS of HL patients treated on S0816 remains high. Nearly 25% of PET2- patients experienced relapse events, demonstrating limitations ABVD therapy and of the negative predictive value of PET2. In PET2+ patients who received eBEACOPP, PFS was favorable, but was associated with a high rate of second malignancies compared with historical controls. Our results emphasize the importance of long-term follow-up, and the need for more efficacious and less toxic therapeutic approaches for advanced-stage HL patients. This trial was registered at www.clinicaltrials.gov as #NCT00822120.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/tratamento farmacológico , Tomografia por Emissão de Pósitrons , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bleomicina/administração & dosagem , Bleomicina/uso terapêutico , Ciclofosfamida/administração & dosagem , Ciclofosfamida/uso terapêutico , Dacarbazina/administração & dosagem , Dacarbazina/uso terapêutico , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Etoposídeo/administração & dosagem , Etoposídeo/uso terapêutico , Feminino , Seguimentos , Doença de Hodgkin/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Tomografia por Emissão de Pósitrons/métodos , Prednisona/administração & dosagem , Prednisona/uso terapêutico , Procarbazina/administração & dosagem , Procarbazina/uso terapêutico , Vimblastina/administração & dosagem , Vimblastina/uso terapêutico , Vincristina/administração & dosagem , Vincristina/uso terapêutico , Adulto Jovem
19.
Clin Neurol Neurosurg ; 184: 105445, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31325903

RESUMO

OBJECTIVE: To explore therapeutic results of different radiotherapy (RT) dose schedules combined to Temozolomide (TMZ)-RT treatment in newly diagnosed glioblastoma (GB), according to the O (6)-methylguanine-DNA methyltransferase (MGMT) methylation status. PATIENTS AND METHODS: Patients with newly diagnosed GB received either standard (60-59.4 Gy) or reduced (54-52 Gy) dose radiation therapy (RT) with concurrent and adjuvant TMZ between June 2010 and October 2016. We retrospectively evaluated the therapeutic effectiveness of the RT ranges schedules in terms of overall survival (OS) with univariate and multivariate analysis, after analyzing the MGMT methylation status. RESULTS: One hundred and seventeen patients were selected for the present analysis out of 146 total treated patients accrued. Seventy-two out of the selected cases received the standard RT-TMZ course (SDRT-TMZ) whereas the remaining 45 underwent the reduced dose schedule (RDRT-TMZ). The analysis according to the MGMT promoter methylation status showed that, in methylated-MGMT GB patients, SDRT-TMZ and RDRT-TMZ groups did not show different median OS (p = ns) according to the two RT schedules, independently by the extent of surgical resection. Instead, a difference in survival outcomes was confirmed in unmethylated-MGMT GB patients with better survival for patients undergoing to SDRT, particularly in sub-total resection. CONCLUSION: In our experience, a reduction of radiation dose schedule does not seem to jeopardize survival in methylated-MGMT patients independently by the extent of resection. A therapeutic approach to a standard reduction of RT dose for the methylated subset of patients may be feasible and could deserve prospective trials for validation.


Assuntos
Neoplasias Encefálicas/radioterapia , Quimiorradioterapia , Dacarbazina/uso terapêutico , Glioblastoma/radioterapia , Adulto , Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/genética , Quimiorradioterapia/métodos , Metilases de Modificação do DNA/genética , Feminino , Glioblastoma/genética , Humanos , Masculino , Pessoa de Meia-Idade
20.
Medicine (Baltimore) ; 98(25): e15873, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31232921

RESUMO

RATIONALE: Ameloblastoma is generally characterized as a benign tumor originating in odontogenic epithelium. However, few cases of metastatic malignant ameloblastoma have also been reported. Due to the low incidence of malignant ameloblastoma, there is no established treatment regimen. To explore effective treatment for malignant ameloblastoma, we reported this case study. PATIENTS CONCERNS: This report described a case of a 28-year-old malignant ameloblastoma female patient with multiple metastasis (brain and lung). DIAGNOSES: The patient presented ameloblastoma of the left mandible in 2012. Three years later, local recurrence and brain metastasis was observed during a follow-up examination. Five years later, malignant ameloblastoma was detected by imaging and immunohistochemistry in the bilateral multiple pulmonary nodules and mediastinal lymph nodes. INTERVENTIONS: The patient was initially treated with tumor resection. Three years later after local recurrence and brain metastasis, she was accepted the extensive mandibulectomy supplemented with brain stereotactic body radiotherapy (SBRT). When diagnosed with pulmonary metastasis, the patient received combined chemotherapy regimen of MAID (mesna, adriamycin, ifosfamide and dacarbazine) for 6 cycles. OUTCOMES: The efficacy evaluation was partial remission (PR) after the 6 cycles of MAID. The last patient follow-up was July 24th 2018, and no evidence of progression was observed. The progression-free survival (PFS) of the patient was more than 9 months. LESSONS: Surgical resection is the optimal treatment for locally recurrent ameloblastoma. SBRT may be an effective treatment for unresectable oligometastasis of malignant ameloblastoma. Finally, combined chemotherapy of MAID showed encouraging effects in the management of metastatic malignant ameloblastoma.


Assuntos
Ameloblastoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Maxilomandibulares/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Ameloblastoma/diagnóstico por imagem , Ameloblastoma/secundário , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/secundário , Dacarbazina/administração & dosagem , Dacarbazina/uso terapêutico , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Feminino , Humanos , Ifosfamida/administração & dosagem , Ifosfamida/uso terapêutico , Neoplasias Maxilomandibulares/diagnóstico por imagem , Neoplasias Maxilomandibulares/patologia , Neoplasias Pulmonares/secundário , Mesna/administração & dosagem , Mesna/uso terapêutico , Metástase Neoplásica , Resultado do Tratamento
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