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1.
Oncotarget ; 15: 220-231, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38484153

RESUMO

ABT199/venetoclax, an inhibitor of the pro-survival BCL-2 protein, has improved AML treatment. Its efficacy in hematopoietic stem cell transplantation (HSCT), when combined with other chemotherapeutic drugs, has not been thoroughly investigated. The present study demonstrates the synergistic cytotoxicity of ABT199/venetoclax with the DNA alkylator thiotepa (Thio) in AML cells. Cleavage of Caspase 3, PARP1 and HSP90, as well as increased Annexin V positivity, suggest potent activation of apoptosis by this two-drug combination; increased levels of γ-H2AX, P-CHK1 (S317), P-CHK2 (S19) and P-SMC1 (S957) indicate an enhanced DNA damage response. Likewise, the increased level of P-SAPK/JNK (T183/Y185) and decreased P-PI3Kp85 (Y458) suggest enhanced activation of stress signaling pathways. These molecular readouts were synergistically enhanced when ABT199/venetoclax and Thio were combined with fludarabine, cladribine and busulfan. The five-drug combination decreased the levels of BCL-2, BCL-xL and MCL-1, suggesting its potential clinical relevance in overcoming ABT199/venetoclax resistance. Moreover, this combination is active against P53-negative and FLT3-ITD-positive cell lines. Enhanced activation of apoptosis was observed in leukemia patient-derived cell samples exposed to the five-drug combination, suggesting a clinical relevance. The results provide a rationale for clinical trials using these two- and five-drug combinations as part of a conditioning regimen for AML patients undergoing HSCT.


Assuntos
Bussulfano , Leucemia Mieloide Aguda , Sulfonamidas , Vidarabina/análogos & derivados , Humanos , Bussulfano/farmacologia , Tiotepa/uso terapêutico , Cladribina/farmacologia , Leucemia Mieloide Aguda/genética , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Combinação de Medicamentos , Linhagem Celular Tumoral , Apoptose
2.
Transplant Cell Ther ; 30(5): 516.e1-516.e10, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38431075

RESUMO

Hepatosplenic T-cell lymphoma (HSTCL) is a rare and aggressive type of peripheral T-cell lymphoma with median overall survival (OS) of approximately 1 year. Data on the effectiveness of hematopoietic cell transplantation (HCT) is limited, as is the choice between autologous HCT (auto-HCT) and allogeneic HCT (allo-HCT) in the treatment of this disease. To evaluate the outcome of patients with HSTCL who underwent either auto-HCT or allo-HCT, we performed a multi-institutional retrospective cohort study to assess outcomes of HCT in HSTCL patients. Fifty-three patients with HSTCL were included in the study. Thirty-six patients received an allo-HCT and 17 received an auto-HCT. Thirty-five (66%) were males. Median age at diagnosis was 38 (range 2 to 64) years. Median follow-up for survivors was 75 months (range 8 to 204). The median number of prior lines of therapy was 1 (range 1 to 4). Median OS and progression-free survival (PFS) for the entire cohort were 78.5 months (95% CI: 25 to 79) and 54 months (95% CI: 18 to 75), respectively. There were no significant differences in OS (HR: 0.63, 95% CI: 0.28 to 1.45, P = .245) or PFS (HR: 0.7, 95% CI: 0.32 to 1.57, P = .365) between the allo-HCT and auto-HCT groups, respectively. In the allo-HCT group, the 3-year cumulative incidence of relapse was 35% (95% CI: 21 to 57), while 3-year cumulative incidence of NRM was 16% (95% CI: 7 to 35). In the auto-HCT group, the 3-year cumulative incidence of relapse and NRM were 43% (95% CI: 23 to 78) and 14% (95% CI: 4 to 52), respectively. Both Auto-HCT and Allo-HCT are effective consolidative strategies in patients with HSTCL, and patients should be promptly referred for HCT evaluation.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Adolescente , Estudos Retrospectivos , Criança , Adulto Jovem , Pré-Escolar , Resultado do Tratamento , Neoplasias Esplênicas/terapia , Estados Unidos/epidemiologia , Linfoma de Células T/terapia , Linfoma de Células T/mortalidade , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/terapia , Transplante Autólogo
5.
Transplant Cell Ther ; 29(12): 770.e1-770.e6, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37742746

RESUMO

Outcomes of myelofibrosis (MF) with allogeneic stem cell transplantation (allo-SCT) have improved over the past decade, related in part to advances in supportive treatments and conditioning regimens. Several factors are known to predict transplantation outcomes. However, most studies lack homogeneity in conditioning regimens used, limiting their ability to assess prognostic factors on transplantation outcomes. We aimed to identify the risk factors that predict transplantation outcomes in patients with MF who underwent matched or mismatched allo-SCT using a uniform myeloablative conditioning regimen consisting of busulfan and fludarabine with tacrolimus and methotrexate-based graft-versus-host disease prophylaxis. This single-center study included patients with MF who underwent allo-SCT with a matched unrelated donor (MUD), matched related donor (MRD), or mismatched unrelated donor (MMUD) and received busulfan and fludarabine conditioning with methotrexate/tacrolimus-based GVHD prophylaxis. Sixty-five patients with MF met the study criteria and were included in our analysis. At a median follow-up of 35.6 months, the 3-year cumulative incidence of relapse (CIR), nonrelapse mortality (NRM), and overall survival (OS) for all study patients were 27%, 20%, and 65%, respectively. In a multivariable analysis for CIR, prior use of JAK inhibitors was significantly associated with a decreased risk of relapse (hazard ratio [HR], .33; 95% confidence interval [CI], .11 to .99; P = .048). For NRM, Hematopoietic Cell Transplantation Comorbidity Index (≥3 versus <3; HR, 10.09; 95% CI, 2.09 to 48.76; P = .004) and donor type (MUD versus MRD: HR, 5.38; 95% CI, 1.14 to 25.30; P = .033; MMUD versus MRD: HR, 10.73; 95% CI, 1.05 to 109.4; P = .045) were associated with an increased risk of mortality. Likewise for OS, HCT-CI (≥3 versus <3; HR, 3.31; 95% CI, 1.22 to 8.99; P = .019) and donor type (MMUD versus MRD: HR, 5.20; 95% CI, 1.35 to 19.98; P = .016) were significantly associated with inferior survival. Longer time from diagnosis to allo-SCT seemed to confer worse survival, but the difference did not reach statistical significance (>12 months versus ≤12 months: NRM: HR, 7.20; 95% CI, .96 to 53.94; P = .055; OS: HR, 2.60; 95% CI, .95 to 7.14; P = .06). In a homogenous cohort of MF patients uniformly treated with busulfan/fludarabine myeloablative conditioning and methotrexate-based GVHD prophylaxis, we show that donor choice and HCT-CI are the 2 strongest predictors for improved survival after allo-SCT.


Assuntos
Doença Enxerto-Hospedeiro , Mielofibrose Primária , Humanos , Bussulfano/uso terapêutico , Tacrolimo/uso terapêutico , Metotrexato/uso terapêutico , Mielofibrose Primária/complicações , Mielofibrose Primária/tratamento farmacológico , Doença Enxerto-Hospedeiro/prevenção & controle , Recidiva
6.
Blood Adv ; 7(20): 6196-6205, 2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-37611156

RESUMO

Traditional conditioning regimens for patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) provide suboptimal outcomes, especially for older patients and those with comorbidities. We hypothesized that a fractionated myeloablative busulfan dose delivered over an extended period would reduce nonrelapse mortality (NRM) while retaining antileukemic effects. Here, we performed a phase 2 trial for adults with hematological malignancies receiving matched related or unrelated allo-HCT. Participants received busulfan 80 mg/m2 as outpatients on days -20 and -13 before transplant. Fludarabine 40 mg/m2 was administered on days -6 to -3, followed by busulfan dosed to achieve a target area under the curve of 20 000 mol/min for the whole course. The primary end point was day-100 NRM. Seventy-eight patients were included, with a median age of 61 years (range, 39-70 years), who received transplantation for acute leukemia (24%), myelodysplastic syndrome (27%), or myeloproliferative disease/chronic myeloid leukemia (44%). HCT-specific comorbidity index (HCT-CI) was ≥3 in 34 (44%). With a median follow-up of 36.4 months (range, 2.9-51.5), the 100-day, 1-year, and 3-year NRM rates were 3.8%, 8%, and 9.3%, respectively, without a significant difference in age or HCT-CI score. The 1-year and 3-year relapse incidence was 10% and 18%, respectively. The 3-year overall survival was 80%, without a significant difference in age or HCT-CI score and was similar for patients aged >60 years and those aged <60 years as well as for those with HCT-CI ≥3 and HCT-CI <3. Overall, a myeloablative fractionated busulfan regimen has low NRM without an increase in relapse rate, resulting in promising survival, even in older patients or in patients with comorbidities. This trial was registered at www.clinicaltrials.gov as #NCT02861417.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Adulto , Idoso , Humanos , Pessoa de Meia-Idade , Bussulfano/uso terapêutico , Comorbidade , Doença Enxerto-Hospedeiro/patologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Recidiva
8.
Blood Adv ; 7(19): 5691-5697, 2023 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-36696472

RESUMO

Patients with hematologic malignancies have both an increased risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and higher morbidity/mortality. They have lower seroconversion rates after vaccination, potentially leading to inferior coronavirus disease 2019 (COVID-19) outcomes, despite vaccination. We consequently evaluated the clinical outcomes of COVID-19 infections in 243 vaccinated and 175 unvaccinated patients with hematologic malignancies. Hospitalization rates were lower in the vaccinated group when compared with the unvaccinated group (31.3% vs 52.6%). However, the rates of COVID-19-associated death were similar at 7.0% and 8.6% in vaccinated and unvaccinated patients, respectively. By univariate logistic regression, females, older patients, and individuals with higher modified Charlson Comorbidity Index scores were at a higher risk of death from COVID-19 infections. To account for the nonrandomized nature of COVID-19 vaccination status, a propensity score weighting approach was used. In the final propensity-weighted model, vaccination status was not significantly associated with the risk of death from COVID-19 infections but was associated with the risk of hospitalization. The predicted benefit of vaccination was an absolute decrease in the probability of death and hospitalization from COVID-19 infections by 2.3% and 22.9%, respectively. In conclusion, COVID-19 vaccination status in patients with hematologic malignancies was associated with a decreased risk of hospitalization but not associated with a decreased risk of death from COVID-19 infections in the pre-Omicron era. Protective strategies, in addition to immunization, are warranted in this vulnerable patient population.


Assuntos
COVID-19 , Neoplasias Hematológicas , Feminino , Humanos , SARS-CoV-2 , Vacinas contra COVID-19 , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/terapia
9.
Blood Adv ; 6(7): 2267-2274, 2022 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-35008100

RESUMO

Secondary central nervous system large B-cell lymphoma (SCNSL) is rare, with a generally poor prognosis. There is limited data about the role of autologous stem cell transplantation (ASCT) in these high-risk patients. We explored in this study treatment outcomes and prognostic factors for patients with SCNSL who underwent ASCT. We included all consecutive patients who underwent ASCT at our institution. Primary endpoints were progression-free survival (PFS) and overall survival (OS). One-hundred two patients were identified. Median age at transplant was 56 (range, 21-71) years. With a median follow-up of 56 (range, 1-256) months, the median PFS and OS were 40 and 88 months, respectively. The 4-year PFS and OS were 48% and 57%, respectively. In univariate analysis, complete remission (CR) at transplant, prior lines of therapy (≤2), normal lactate dehydrogenase, and parenchymal involvement were significantly associated with improved PFS. For OS, only CR at transplant and ≤2 prior lines of therapy were associated with improved survival. On multivariable analysis for PFS, CR at transplant (hazard ratio [HR], 0.278; 95% CI, 0.153-0.506; P ≤ .0001) and ≤2 prior lines of therapy (HR, 0.485; 95% CI, 0.274-0.859; P = .0131) were significantly associated with superior PFS. Similarly, CR at transplant (HR, 0.352; 95% CI, 0.186-0.663; P = .0013) and ≤2 prior lines of therapy (HR, 0.476; 95% CI, 0.257-0.882; P = .0183) were associated with improved survival. In the largest single-center study, our findings indicate that ASCT is associated with durable responses and prolonged survival in patients with SCNSL. Patients in CR at transplant and those who received ≤2 lines of therapy have particularly excellent outcomes.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma Difuso de Grandes Células B , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Sistema Nervoso Central , Humanos , Linfoma Difuso de Grandes Células B/terapia , Transplante Autólogo
10.
Leuk Lymphoma ; 63(3): 710-721, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34686083

RESUMO

Standard-of-care for newly-diagnosed, autologous hematopoietic stem cell transplantation (auto-HCT)-eligible, multiple myeloma (MM) patients includes bortezomib, lenalidomide, and dexamethasone (VRD) induction followed by melphalan 200 mg/m2 (Mel200)-conditioned auto-HCT and lenalidomide maintenance. We completed a retrospective case series assessing outcomes of 187 MM patients who received this regimen at our institution. The 100-day non-relapse mortality incidence was zero. Before auto-HCT, 9.6 and 52.9% of patients achieved a complete response (CR) or ≥ very good partial response (VGPR), respectively. At day-100 post-transplant, 29.4 and 74.9% had achieved a CR/stringent-CR (sCR) or ≥ VGPR, respectively. At the last evaluation, 57.2% of patients had CR/sCR and 87.1% had ≥ VGPR. Median follow-up, progression-free survival (PFS), and overall survival (OS) were 63.2, 50, and 101.7 months, respectively. The 5-year PFS and OS were 43.1 and 79%. High-risk cytogenetics was associated with worse outcomes. This study illustrates that VRD induction, Mel200-conditioned auto-HCT, and lenalidomide maintenance are associated with good outcomes in MM.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bortezomib/uso terapêutico , Dexametasona/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Lenalidomida/efeitos adversos , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/tratamento farmacológico , Estudos Retrospectivos , Transplante Autólogo
11.
Blood Adv ; 5(14): 2799-2806, 2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34264268

RESUMO

The Endothelial Activation and Stress Index (EASIX) score, defined as [(creatinine × lactate dehydrogenase [LDH])/platelets], is a marker of endothelial activation that has been validated in the allogeneic hematopoietic stem cell transplant setting. Endothelial activation is one of the mechanisms driving immune-mediated toxicities in patients treated with chimeric antigen receptor-T (CAR-T)-cell therapy. This study's objective was to evaluate the association between EASIX and other laboratory parameters collected before lymphodepletion and the subsequent onset of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) those patients. Toxicity data were collected prospectively on 171 patients treated with axicabtagene ciloleucel (axi-cel) for large B-cell lymphoma (LBCL). CRS grades 2 to 4 were diagnosed in 81 (47%) patients and ICANS grades 2 to 4 in 84 (49%). EASIX combined with ferritin (EASIX-F) identified 3 risk groups with CRS grades 2 to 4 cumulative incidence of 74% (hazards ratio [HR], 4.8; 95% confidence interval [CI], 2.1-11; P < .001), 49% (HR, 2.3; 95% CI, 1.02-5; P = .04), and 23% (reference), respectively. EASIX combined with CRP and ferritin (EASIX-FC) identified 3 risk groups with an ICANS grade 2 to 4 cumulative incidence of 74% (HR, 3.6; 95% CI, 1.9-6.9; P < .001), 51% (HR, 2.1; 95% CI, 1.1-3.9; P = .025), and 29% (reference). Our results indicate that common laboratory parameters before lymphodepletion correlate with CAR-T-related toxicities and can help support clinical decisions, such as preemptive toxicity management, hospitalization length, and proper setting for CAR-T administration.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma Difuso de Grandes Células B , Receptores de Antígenos Quiméricos , Síndrome da Liberação de Citocina , Ferritinas , Humanos
12.
Front Immunol ; 12: 675679, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33995420

RESUMO

Background: COVID-19 Convalescent plasma (CCP) is safe and effective, particularly if given at an early stage of the disease. Our study aimed to identify an association between survival and specific antibodies found in CCP. Patients and Methods: Patients ≥18 years of age who were hospitalized with moderate to severe COVID-19 infection and received CCP at the MD Anderson Cancer Center between 4/30/2020 and 8/20/2020 were included in the study. We quantified the levels of anti-SARS-CoV-2 antibodies, as well as antibodies against antigens of other coronavirus strains, in the CCP units and compared antibody levels with patient outcomes. For each antibody, a Bayesian exponential survival time regression model including prognostic variables was fit, and the posterior probability of a beneficial effect (PBE) of higher antibody level on survival time was computed. Results: CCP was administered to 44 cancer patients. The median age was 60 years (range 37-84) and 19 (43%) were female. Twelve patients (27%) died of COVID-19-related complications. Higher levels of two non-SARS-CoV-2-specific antibodies, anti-HCoV-OC43 spike IgG and anti-HCoV-HKU1 spike IgG, had PBE = 1.00, and 4 SARS-CoV-2-specific antibodies had PBEs between 0.90 and 0.95. Other factors associated with better survival were shorter time to CCP administration, younger age, and female sex. Conclusions: Common cold coronavirus spike IgG antibodies anti-HCoV-OC43 and anti-HCoV-HKU1 may target a common domain for SARS-CoV-2 and other coronaviruses. They provide a promising therapeutic target for monoclonal antibody production.


Assuntos
Anticorpos Antivirais , Betacoronavirus/imunologia , COVID-19/terapia , Resfriado Comum/imunologia , Convalescença , Coronavirus Humano OC43/imunologia , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/administração & dosagem , Anticorpos Antivirais/imunologia , COVID-19/imunologia , COVID-19/mortalidade , Reações Cruzadas , Feminino , Humanos , Imunização Passiva , Masculino , Pessoa de Meia-Idade , Soroterapia para COVID-19
13.
Bone Marrow Transplant ; 56(8): 2005-2012, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33846563

RESUMO

Despite low nonrelapse mortality (NRM) at day 100 after allogeneic hematopoietic cell transplantation (HCT), NRM at 1 year remains substantial. In this study, we retrospectively analyzed 199 patients who were treated on a phase II clinical trial assessing safety and efficacy of myeloablative fractionated busulfan and fludarabine conditioning regimen for hematologic malignancies. The goal of the study was to identify factors associated with NRM occurring between days 101 and 365 post-HCT and generate a hypothesis for future studies to reduce the risk of NRM at 1 year. We found that a vast majority (83%) of patients who experienced NRM between days 101 and 365 had prior grade II-IV acute graft-versus-host disease (GVHD), which was the leading cause of death either by itself (33.3%) or complicated by infections (37.5%). In multivariate analysis, grade II-IV acute GVHD (hazard ratio (HR) 2.9, 95% confidence interval (CI) 1.3-6.6, p = 0.01) was the only significant predictor of NRM between days 101 and 365. Measures to reduce the risk of acute GVHD could lower the risk of NRM at 1 year and improve overall survival.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Bussulfano , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Estudos Retrospectivos , Análise de Sobrevida , Condicionamento Pré-Transplante/efeitos adversos , Transplante Homólogo
14.
medRxiv ; 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33758890

RESUMO

BACKGROUND: COVID-19 Convalescent plasma (CCP) is safe and effective, particularly if given at an early stage of the disease. Our study aimed to identify an association between survival and specific antibodies found in CCP. PATIENTS AND METHODS: Patients ≥18 years of age who were hospitalized with moderate to severe COVID-19 infection and received CCP at the MD Anderson Cancer Center between 4/30/2020 and 8/20/2020 were included in the study. We quantified the levels of anti-SARS-CoV-2 antibodies, as well as antibodies against antigens of other coronavirus strains, in the CCP units and compared antibody levels with patient outcomes. For each antibody, a Bayesian exponential survival time regression model including prognostic variables was fit, and the posterior probability of a beneficial effect (PBE) of higher antibody level on survival time was computed. RESULTS: CCP was administered to 44 cancer patients. The median age was 60 years (range 37-84) and 19 (43%) were female. Twelve patients (27%) died of COVID-19-related complications. Higher levels of two non-SARS-CoV-2-specific antibodies, anti-HCoV-OC43 spike IgG and anti-HCoV-HKU1 spike IgG, had PBE = 1.00, and 4 SARS-CoV-2-specific antibodies had PBEs between 0.90 and 0.95. Other factors associated with better survival were shorter time to CCP administration, younger age, and female sex. CONCLUSIONS: Common cold coronavirus spike IgG antibodies anti-HCoV-OC43 and anti-HCoV-HKU1 may target a common domain for SARS-CoV-2 and other coronaviruses. They provide a promising therapeutic target for monoclonal antibody production.

15.
Case Rep Hematol ; 2019: 4861673, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31662918

RESUMO

Transient cytopenias and bone marrow hypoplasia commonly occur during treatment of CML with TKIs (tyrosine kinase inhibitors). This is usually related to the eradication of CML clones that initially compose the majority of hematopoietic cells in the bone marrow at the time of diagnosis. With continuation of effective therapy, normal blood counts return as normal hematopoiesis is restored and CML clones are reduced. Though rare and more unusual than myelodysplastic syndrome (MDS), isolated instances of persistent marrow aplasia have been documented with chronic use of TKIs. We describe two such instances of chronic phase CML where no significant reduction of CML clones was achieved following treatment with TKIs, but bone marrow aplasia occurred resulting in persistent dysfunctional hematopoiesis. Due to prolonged aplasia/hypoplasia, such patients are no longer amenable to TKI treatment. CML progression to accelerated or blast phase in that setting would likely be fatal.

16.
Breast Cancer Res Treat ; 176(2): 253-260, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30900138

RESUMO

PURPOSE: Metastatic breast cancer is regarded as an incurable entity. In heavily pretreated patients with increasingly limited options for palliative management, ensuring proper quality of life continues is to be an elusive issue. With this in mind, the authors evaluated the efficacy and safety of the Vinorelbine/Capecitabine doublet (VINOCAP). PATIENTS AND METHODS: The investigators retrospectively analyzed a cohort of 67 women with HER2 negative MBC treated at a large breast cancer practice and a local cancer center with Vinorelbine 22.5 mg/m2 IV on days 1 and 8 combined with Capecitabine 1 g PO BID for 14 consecutive days of 21 day cycles. Patients had been treated with an average of 4 prior lines of chemotherapy. Patient characteristics and outcomes were evaluated. RESULTS: A total of 67 patients received VINOCAP, and an additional 2 underwent repeat exposure yielding a cohort of 69. Clinical benefit rate, defined as complete response (CR), partial response (PR) or stable disease ≥ 6 months (SD), was 55.07%. Complete response was seen in 4.34%, PR in 18.8% and SD ≥ 6 months in 31.9%. Median progression-free survival was 6.2 months and overall survival 35.47 months after VINOCAP exposure. The most common grade 3-4 toxicity was neutropenia in 10% of cases. Dose had to be reduced in 18% of cases due to toxicity of any type. The regimen was well tolerated, and serious side effects were uncommon. CONCLUSION: Vinorelbine/Capecitabine appears to be an active and well-tolerated regimen in women with MBC. In particular, encouraging was the efficacy of VINOCAP as fourth or greater line of chemotherapy.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Antineoplásicos Fitogênicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Capecitabina/administração & dosagem , Vinorelbina/administração & dosagem , Adulto , Idoso , Antimetabólitos Antineoplásicos/efeitos adversos , Antineoplásicos Fitogênicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/genética , Capecitabina/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Qualidade de Vida , Receptor ErbB-2/genética , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Vinorelbina/efeitos adversos
17.
Rare Tumors ; 10: 2036361318787626, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30038741

RESUMO

In patients with sarcoma, concomitant malignancy is found in 1.2% -2.5% of cases. Previous studies have demonstrated conflicting results in terms of positive or negative effects on cancer prognosis with comorbid sarcoidosis. Additionally, there are no data determining whether an association between sarcoidosis and sarcomas exists. Finding an association between the two entities could prevent inadvertent upstaging of a primary sarcoma based on pulmonary nodularity mistaken for metastatic disease. Here, we will describe eight sarcoma patients with concomitant occurrence of sarcoidosis identified since 2007. Eight patients with diagnosis of both sarcoma and sarcoidosis were identified over the period of 2007 -2016 at a single sarcoma center. Clinical and historical data including presentation, histology, treatment, and outcome was tabulated for analysis. The standardized incidence ratio was calculated for the state of Florida and our hospital catchment area. We compared the observed incidence to the expected incidence if the two entities were to be unrelated. Sarcoma subtype was gastrointestinal stromal tumor in five patients, the remaining three cases were unclassified spindled and epithelioid cell sarcoma, uterine leiomyosarcoma, and myxofibrosarcoma. Sarcoidosis was diagnosed before sarcoma in three patients, after sarcoma in four patients, and at the same time of sarcoma diagnosis in one patient. From our series, three patients have shown no progression of sarcoma, two are alive with sarcoma, two died due to progression of sarcoma, and one was lost to follow up. Statistical analyses showed a standardized incidence ratio of 305 (95% confidence interval: 131 -556) for the state of Florida and standardized incidence ratio of 950 (95% CI: 407 -1727) for our catchment area. This case series points to a statistically robust, nonrandom association between sarcoma and sarcoidosis that has not been previously described. Presumed metastatic sarcoma should be considered for biopsy particularly with demographic characteristics or imaging features suggestive of sarcoidosis.

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