Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 15 de 15
Filtrar
1.
Blood Adv ; 2024 04 19.
Artículo en Inglés | MEDLINE | ID: mdl-38640348

RESUMEN

Ivosidenib is a first-in-class mutant isocitrate dehydrogenase 1 (mIDH1) inhibitor and has shown efficacy and tolerability in patients with advanced mIDH1 hematologic malignancies, leading to approval in front-line and relapsed/refractory (R/R) mIDH1 AML populations. We report final data from a phase I single-arm substudy (NCT02074839) of patients with R/R mIDH1 MDS following failure of standard-of-care therapies. Oral ivosidenib was taken once daily on days 1-28 in 28-day cycles. Primary objectives were to determine safety, tolerability, and clinical activity. The primary efficacy endpoint was the complete remission + partial remission (CR+PR) rate. Nineteen patients were enrolled; 18 were included in the efficacy analysis. Treatment-related adverse events occurred in eight (42.1%) patients, including a grade 1 QT interval prolongation in one (5.3%) patient and grade 2 differentiation syndrome in two (10.5%) patients. Rates of CR+PR and objective response (CR +PR+marrow CR) were 38.9% (95% confidence interval [CI]: 17.3, 64.3) and 83.3% (95% CI: 58.6, 96.4), respectively. Kaplan-Meier estimates showed a 68.6% probability of patients in CR achieving a remission duration of >=5 years, and a median OS of 35.7 months. Of note, 71.4% and 75.0% baseline red blood cell (RBC) and platelet transfusion-dependent patients, respectively, became transfusion independent (TI; no transfusion >=56 days); 81.8% and 100% of baseline RBC and platelet TI patients, respectively, remained TI. One (5.3%) patient proceeded to a hematopoietic stem cell transplant by data cut-off. In conclusion, ivosidenib is clinically active, with durable remissions and a manageable safety profile observed in patients with mIDH1 R/R MDS.

2.
Lancet Haematol ; 11(1): e15-e26, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38135371

RESUMEN

BACKGROUND: The DNA methyltransferase inhibitors azacitidine and decitabine for individuals with myelodysplastic syndromes or chronic myelomonocytic leukaemia are available in parenteral form. Oral therapy with similar exposure for these diseases would offer potential treatment benefits. We aimed to compare the safety and pharmacokinetics of oral decitabine plus the cytidine deaminase inhibitor cedazuridine versus intravenous decitabine. METHODS: We did a registrational, multicentre, open-label, crossover, phase 3 trial of individuals with myelodysplastic syndromes or chronic myelomonocytic leukaemia and individuals with acute myeloid leukaemia, enrolled as separate cohorts; results for only participants with myelodysplastic syndromes or chronic myelomonocytic leukaemia are reported here. In 37 academic and community-based clinics in Canada and the USA, we enrolled individuals aged 18 years or older who were candidates to receive intravenous decitabine, with Eastern Cooperative Oncology Group performance status 0 or 1 and a life expectancy of at least 3 months. Participants were randomly assigned (1:1) to receive 5 days of oral decitabine-cedazuridine (one tablet once daily containing 35 mg decitabine and 100 mg cedazuridine as a fixed-dose combination) or intravenous decitabine (20 mg/m2 per day by continuous 1-h intravenous infusion) in a 28-day treatment cycle, followed by 5 days of the other formulation in the next treatment cycle. Thereafter, all participants received oral decitabine-cedazuridine from the third cycle on until treatment discontinuation. The primary endpoint was total decitabine exposure over 5 days with oral decitabine-cedazuridine versus intravenous decitabine for cycles 1 and 2, measured as area under the curve in participants who received the full treatment dose in cycles 1 and 2 and had decitabine daily AUC0-24 for both oral decitabine-cedazuridine and intravenous decitabine (ie, paired cycles). On completion of the study, all patients were rolled over to a maintenance study. This study is registered with ClinicalTrials.gov, NCT03306264. FINDINGS: Between Feb 8, 2018, and June 7, 2021, 173 individuals were screened, 138 (80%) participants were randomly assigned to a treatment sequence, and 133 (96%) participants (87 [65%] men and 46 [35%] women; 121 [91%] White, four [3%] Black or African-American, three [2%] Asian, and five [4%] not reported) received treatment. Median follow-up was 966 days (IQR 917-1050). Primary endpoint of total exposure of oral decitabine-cedazuridine versus intravenous decitabine was 98·93% (90% CI 92·66-105·60), indicating equivalent pharmacokinetic exposure on the basis of area under the curve. The safety profiles of oral decitabine-cedazuridine and intravenous decitabine were similar. The most frequent adverse events of grade 3 or worse were thrombocytopenia (81 [61%] of 133 participants), neutropenia (76 [57%] participants), and anaemia (67 [50%] participants). The incidence of serious adverse events in cycles 1-2 was 31% (40 of 130 participants) with oral decitabine-cedazuridine and 18% (24 of 132 participants) with intravenous decitabine. There were five treatment-related deaths; two deemed related to oral therapy (sepsis and pneumonia) and three to intravenous treatment (septic shock [n=2] and pneumonia [n=1]). INTERPRETATION: Oral decitabine-cedazuridine was pharmacologically and pharmacodynamically equivalent to intravenous decitabine. The results support use of oral decitabine-cedazuridine as a safe and effective alternative to intravenous decitabine for treatment of individuals with myelodysplastic syndromes or chronic myelomonocytic leukaemia. FUNDING: Astex Pharmaceuticals.


Asunto(s)
Leucemia Mielomonocítica Crónica , Síndromes Mielodisplásicos , Neumonía , Masculino , Humanos , Femenino , Decitabina/efectos adversos , Resultado del Tratamiento , Leucemia Mielomonocítica Crónica/tratamiento farmacológico , Síndromes Mielodisplásicos/tratamiento farmacológico , Síndromes Mielodisplásicos/etiología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neumonía/etiología
3.
Eur J Haematol ; 111(6): 844-850, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37587783

RESUMEN

INTRODUCTION: Four to 10% of cases of myeloid malignancies are inherited. We report our experience on hereditary myeloid malignancy syndromes (HMMS) incorporating a novel questionnaire in the screening platform for patients with myeloid malignancies and aplastic anemia. METHODS: The questionnaire was sent via electronic patient portal prior to clinic visits. Patients screened positive based on responses to questionnaire items, presence of suspicion disease characteristics (young age, family history, monosomy 7 etc.) and/or presence of signs of HMMS. Those deemed at-risk based on questionnaire responses, clinical features and/or somatic mutation profile were offered germline testing. RESULTS: A total of 408 patients were screened, 141 (35%) were deemed at-risk. Fifty-four (38%) of at-risk patients were seen in the genetics clinic. Forty-one (76%) of the patients seen agreed to germline testing and 13 declined due to cost or personal decision. Twenty pathogenic (P)/likely-pathogenic (LP) germline mutations were identified in 16 (39%) of the tested patients. Five patients also had a variant of uncertain significance (VUS) and an additional 13 had at least 1 VUS without P/LP mutations (total 29 VUS's were found in 18 (44%) of tested patients). The median age of diagnosis for patients with P/LP mutations was 56 years versus 66 years in the entire cohort. CONCLUSION: Incorporating an electronic questionnaire is an effective screening method for HMMS. Many patients declined testing due to cost. These results highlight the importance of germline testing in patients with myeloid malignancies, further research in HMMS, and coverage by healthcare plans.


Asunto(s)
Trastornos Mieloproliferativos , Neoplasias , Humanos , Persona de Mediana Edad , Predisposición Genética a la Enfermedad , Trastornos Mieloproliferativos/genética , Mutación , Mutación de Línea Germinal , Síndrome
4.
Acta Med Acad ; 52(1): 30-36, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37326395

RESUMEN

OBJECTIVE: Patients diagnosed with hematologic malignancies are at increased risk for severe SARS-CoV-2 infection. We evaluated the serological IgG response following two doses of the SARS-CoV-2 vaccine in patients with hematologic malignancies. METHODS: Patients treated at UT Southwestern Medical Center with a diagnosis of a myeloid or lymphoid neoplasm were included. SARS-CoV-2 vaccination response was defined as a positive quantifiable spike IgG antibody titer. RESULTS: Sixty patients were included in the study and 60% were diagnosed with a myeloid neoplasm. The majority (85%) of the patients with a myeloid malignancy and 50% of the patients with a lymphoid malignancy mounted a serological response after receiving two doses of the vaccine. CONCLUSION: Vaccination should be offered irrespective of ongoing treatment or active disease. Findings require validation in a larger cohort of patients.


Asunto(s)
COVID-19 , Neoplasias Hematológicas , Humanos , Vacunas contra la COVID-19 , Inmunoglobulina G , SARS-CoV-2 , Formación de Anticuerpos , COVID-19/prevención & control , Vacunación
5.
Leuk Lymphoma ; 64(6): 1123-1128, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37052347

RESUMEN

Venetoclax (VEN) in combination with hypomethylating agents (HMA) or low-dose cytarabine has become the standard of care for patients with acute myeloid leukemia (AML) who are ineligible to receive intensive induction chemotherapy. Clinical trials are performed in a controlled setting that can be difficult to emulate in the real world. We sought to investigate outcomes of patients treated with VEN-based therapy in the real world. Patients with an age of ≥65 years who received frontline VEN-based therapy were identified using the COTA database (n = 112). The majority of patients (91%) were treated in the community setting and had adverse-risk AML (63%). The real-world overall response rate (rwORR) was 55% with a median real-world overall survival (rwOS) of 13 months after VEN/HMA. The rwORR was lower and median rwOS was shorter than those reported in the VIALE-A trial, underscoring the importance of studying novel therapies using real-world data.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Leucemia Mieloide Aguda , Anciano , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Compuestos Bicíclicos Heterocíclicos con Puentes/efectos adversos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/etiología , Sulfonamidas/efectos adversos
6.
Cancer ; 129(15): 2308-2320, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-37078412

RESUMEN

BACKGROUND: Patients with acute myeloid leukemia (AML) who have tumor protein p53 (TP53) mutations or a complex karyotype have a poor prognosis, and hypomethylating agents are often used. The authors evaluated the efficacy of entospletinib, an oral inhibitor of spleen tyrosine kinase, combined with decitabine in this patient population. METHODS: This was a multicenter, open-label, phase 2 substudy of the Beat AML Master Trial (ClinicalTrials.gov identifier NCT03013998) using a Simon two-stage design. Eligible patients aged 60 years or older who had newly diagnosed AML with mutations in TP53 with or without a complex karyotype (cohort A; n = 45) or had a complex karyotype without TP53 mutation (cohort B; n = 13) received entospletinib 400 mg twice daily with decitabine 20 mg/m2 on days 1-10 every 28 days for up to three induction cycles, followed by up to 11 consolidation cycles, in which decitabine was reduced to days 1-5. Entospletinib maintenance was given for up to 2 years. The primary end point was complete remission (CR) and CR with hematologic improvement by up to six cycles of therapy. RESULTS: The composite CR rates for cohorts A and B were 13.3% (95% confidence interval, 5.1%-26.8%) and 30.8% (95% confidence interval, 9.1%-61.4%), respectively. The median duration of response was 7.6 and 8.2 months, respectively, and the median overall survival was 6.5 and 11.5 months, respectively. The study was stopped because the futility boundary was crossed in both cohorts. CONCLUSIONS: The combination of entospletinib and decitabine demonstrated activity and was acceptably tolerated in this patient population; however, the CR rates were low, and overall survival was short. Novel treatment strategies for older patients with TP53 mutations and complex karyotype remain an urgent need.


Asunto(s)
Leucemia Mieloide Aguda , Proteína p53 Supresora de Tumor , Humanos , Decitabina , Proteína p53 Supresora de Tumor/genética , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Cariotipo , Resultado del Tratamiento , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos
7.
Transpl Immunol ; 77: 101808, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36842566

RESUMEN

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only curative option for high-risk myeloid malignancies. Post-transplant cyclophosphamide (PT-Cy) has proven to be effective for graft versus host disease (GVHD) prophylaxis. Given that graft-versus-tumor (GVT) effect plays a major role in reducing the risk of disease relapse, the application of PT-Cy must balance the risk of relapse. Mixed chimerism (MC) refers to a state of concurrent presence of recipient and donor cells post allo-HSCT which may precede relapse disease. OBJECTIVE: We investigated the impact of PT-Cy on early MC (EMC) and disease relapse in patients with a myeloid malignancy post allo-HSCT. STUDY DESIGN: This retrospective single-center study included patients that underwent allo-HSCT between 2015 and 2021. Patient and disease characteristics were collected from the electronic health records. EMC was defined as <95% donor cells at day 90-120 post allo-HSCT. RESULTS: A total of 144 patient that received an allo-HSCT were included in the study. One hundred and eight (75%) patients received PT-Cy as part of the GVHD prophylaxis regimen. The majority underwent allo-HSCT for acute myeloid leukemia (62%) or myelodysplastic syndrome (31%). Sixty-five percent received allo-HSCT from a matched unrelated donor transplant and 65% received a myeloablative conditioning regimen. A lower rate of chronic GVHD (p = 0.03) and a higher rate of EMC (p = 0.04) were observed in patients that received PT-Cy. PT-Cy was not associated with overall survival (OS) and relapse-free survival (RFS). Multivariable analysis identified measurable residual disease status (p = 0.003), hematopoietic cell transplantation-specific comorbidity index (p = 0.012) and chronic GVHD (p = 0.006) as independent prognostic variables for OS. AML-adverse risk (p = 0.004) and EMC (p = 0.018) were independently prognostic for RFS. While EMC overall was not significantly associated with higher risk of relapse, EMC was associated with shorter RFS within adverse-risk AML patients. CONCLUSION: Our study shows that PT-Cy was associated with an increased risk of EMC. The predictive value of EMC for relapse remains unclear and may depend on the underlying disease, which should be validated in a larger cohort.


Asunto(s)
Quimerismo , Ciclofosfamida , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Síndromes Mielodisplásicos , Ciclofosfamida/administración & dosificación , Ciclofosfamida/uso terapéutico , Trasplante Homólogo , Enfermedad Injerto contra Huésped/prevención & control , Recurrencia , Registros Electrónicos de Salud , Estudios Retrospectivos , Leucemia Mieloide Aguda/patología , Leucemia Mieloide Aguda/terapia , Síndromes Mielodisplásicos/patología , Síndromes Mielodisplásicos/terapia , Acondicionamiento Pretrasplante , Medición de Riesgo , Humanos , Masculino , Femenino , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Tasa de Supervivencia , Análisis de Regresión
9.
Leuk Lymphoma ; 63(7): 1651-1659, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35133215

RESUMEN

Race and ethnic backgrounds affect the disease characteristics and clinical outcomes in many cancers, including acute myeloid leukemia; however, the association of race/ethnicity on myelodysplastic syndrome (MDS) is still controversial. Therefore, we aimed to study the impact of race/ethnicity on the disease characteristics and survival outcomes in patients with MDS. Adult patients with MDS diagnosed in 2004-2016 were selected using the SEER database. Race/ethnicity was categorized as non-Hispanic White (NHW), non-Hispanic Black (NHB), and Hispanic. Hispanic and NHB patients had significantly lower incidence rate ratio (IRR) in age group ≥01 years (p < .001) compared to NHW; however, in the age group <50 years, NHB patients had significantly higher IRR with an increased incidence rate of 49%. NHB patients had better overall survival than Hispanic and NHW patients (p < .001), even after adjusting for confounding variables. MDS have significant differences in age at diagnosis, disease risk, and survival outcomes based on racial/ethnic backgrounds.


Asunto(s)
Etnicidad , Síndromes Mielodisplásicos , Adulto , Negro o Afroamericano , Hispánicos o Latinos , Humanos , Lactante , Persona de Mediana Edad , Síndromes Mielodisplásicos/diagnóstico , Síndromes Mielodisplásicos/epidemiología , Síndromes Mielodisplásicos/terapia , Población Blanca
10.
Blood ; 137(13): 1792-1803, 2021 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-33024987

RESUMEN

Ivosidenib (AG-120) and enasidenib (AG-221) are targeted oral inhibitors of the mutant isocitrate dehydrogenase (mIDH) 1 and 2 enzymes, respectively. Given their effectiveness as single agents in mIDH1/2 relapsed or refractory acute myeloid leukemia (AML), this phase 1 study evaluated the safety and efficacy of ivosidenib or enasidenib combined with intensive chemotherapy in patients with newly diagnosed mIDH1/2 AML. Ivosidenib 500 mg once daily and enasidenib 100 mg once daily were well tolerated in this setting, with safety profiles generally consistent with those of induction and consolidation chemotherapy alone. The frequency of IDH differentiation syndrome was low, as expected given the concurrent administration of cytotoxic chemotherapy. In patients receiving ivosidenib, the frequency and grades of QT interval prolongation were similar to those observed with ivosidenib monotherapy. Increases in total bilirubin were more frequently observed in patients treated with enasidenib, consistent with this inhibitor's known potential to inhibit UGT1A1, but did not appear to have significant clinical consequences. In patients receiving ivosidenib (n = 60) or enasidenib (n = 91), end-of-induction complete remission (CR) rates were 55% and 47%, respectively, and CR/CR with incomplete neutrophil or platelet recovery (CR/CRi/CRp) rates were 72% and 63%, respectively. In patients with a best overall response of CR/CRi/CRp, 16/41 (39%) receiving ivosidenib had IDH1 mutation clearance and 15/64 (23%) receiving enasidenib had IDH2 mutation clearance by digital polymerase chain reaction; furthermore, 16/20 (80%) and 10/16 (63%), respectively, became negative for measurable residual disease by multiparameter flow cytometry. This trial was registered at www.clinicaltrials.gov as #NCT02632708.


Asunto(s)
Aminopiridinas/uso terapéutico , Antineoplásicos/uso terapéutico , Glicina/análogos & derivados , Leucemia Mieloide Aguda/tratamiento farmacológico , Piridinas/uso terapéutico , Triazinas/uso terapéutico , Adulto , Anciano , Aminopiridinas/efectos adversos , Antineoplásicos/efectos adversos , Femenino , Glicina/efectos adversos , Glicina/uso terapéutico , Humanos , Isocitrato Deshidrogenasa/genética , Leucemia Mieloide Aguda/genética , Masculino , Persona de Mediana Edad , Mutación/efectos de los fármacos , Piridinas/efectos adversos , Resultado del Tratamiento , Triazinas/efectos adversos , Adulto Joven
11.
J Clin Oncol ; 39(1): 57-65, 2021 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-33119479

RESUMEN

PURPOSE: Ivosidenib is an oral inhibitor of the mutant isocitrate dehydrogenase 1 (IDH1) enzyme, approved for treatment of IDH1-mutant (mIDH1) acute myeloid leukemia (AML). Preclinical work suggested that addition of azacitidine to ivosidenib enhances mIDH1 inhibition-related differentiation and apoptosis. PATIENTS AND METHODS: This was an open-label, multicenter, phase Ib trial comprising dose-finding and expansion stages to evaluate safety and efficacy of combining oral ivosidenib 500 mg once daily continuously with subcutaneous azacitidine 75 mg/m2 on days 1-7 in 28-day cycles in patients with newly diagnosed mIDH1 AML ineligible for intensive induction chemotherapy (ClinicalTrials.gov identifier: NCT02677922). RESULTS: Twenty-three patients received ivosidenib plus azacitidine (median age, 76 years; range, 61-88 years). Treatment-related grade ≥ 3 adverse events occurring in > 10% of patients were neutropenia (22%), anemia (13%), thrombocytopenia (13%), and electrocardiogram QT prolongation (13%). Adverse events of special interest included all-grade IDH differentiation syndrome (17%), all-grade electrocardiogram QT prolongation (26%), and grade ≥ 3 leukocytosis (9%). Median treatment duration was 15.1 months (range, 0.3-32.2 months); 10 patients remained on treatment as of February 19, 2019. The overall response rate was 78.3% (18/23 patients; 95% CI, 56.3% to 92.5%), and the complete remission rate was 60.9% (14/23 patients; 95% CI, 38.5% to 80.3%). With median follow-up of 16 months, median duration of response in responders had not been reached. The 12-month survival estimate was 82.0% (95% CI, 58.8% to 92.8%). mIDH1 clearance in bone marrow mononuclear cells by BEAMing (beads, emulsion, amplification, magnetics) digital polymerase chain reaction was seen in 10/14 patients (71.4%) achieving complete remission. CONCLUSION: Ivosidenib plus azacitidine was well tolerated, with an expected safety profile consistent with monotherapy with each agent. Responses were deep and durable, with most complete responders achieving mIDH1 mutation clearance.


Asunto(s)
Azacitidina/administración & dosificación , Inhibidores Enzimáticos/administración & dosificación , Glicina/análogos & derivados , Leucemia Mieloide Aguda/tratamiento farmacológico , Piridinas/administración & dosificación , Anciano , Anciano de 80 o más Años , Apoptosis/efectos de los fármacos , Quimioterapia Combinada , Femenino , Glicina/administración & dosificación , Humanos , Isocitrato Deshidrogenasa/genética , Leucemia Mieloide Aguda/genética , Masculino , Persona de Mediana Edad
12.
Clin Cancer Res ; 26(23): 6132-6140, 2020 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-32998961

RESUMEN

PURPOSE: The Polo-like kinase 1 (PLK1) is a master regulator of mitosis and overexpressed in acute myeloid leukemia (AML). We conducted a phase Ib study of the PLK1 inhibitor, onvansertib, in combination with either low-dose cytarabine (LDAC) or decitabine in patients with relapsed or refractory (R/R) AML. PATIENTS AND METHODS: Onvansertib was administered orally, in escalating doses, on days 1-5 in combination with either LDAC (20 mg/m2; days 1-10) or decitabine (20 mg/m2; days 1-5) in a 28-day cycle. The primary endpoint was to evaluate first-cycle dose-limiting toxicities and the MTD. Secondary and exploratory endpoints included safety, pharmacokinetics, antileukemic activity, and response biomarkers. RESULTS: Forty patients were treated with onvansertib (12-90 mg/m2) in combination with LDAC (n = 17) or decitabine (n = 23). Onvansertib was well tolerated with most grades 3 and 4 adverse events related to myelosuppression. In the decitabine arm, the MTD was established at 60 mg/m2, and 5 (24%) of the 21 evaluable patients achieved complete remission with or without hematologic count recovery. Decrease in mutant circulating tumor DNA (ctDNA) during the first cycle of therapy was associated with clinical response. Engagement of the PLK1 target, TCTP, was measured in circulating blasts and was associated with greater decrease in bone marrow blasts. CONCLUSIONS: The onvansertib and decitabine combination was well tolerated and had antileukemic activity particularly in patients with target engagement and decreased mutant ctDNA following treatment. This combination will be further investigated in the ongoing phase II trial.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Resistencia a Antineoplásicos/efectos de los fármacos , Leucemia Mieloide Aguda/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Terapia Recuperativa , Adulto , Anciano , Anciano de 80 o más Años , Citarabina/administración & dosificación , Decitabina/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Leucemia Mieloide Aguda/patología , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Piperazinas/administración & dosificación , Pronóstico , Pirazoles/administración & dosificación , Quinazolinas/administración & dosificación
14.
ACG Case Rep J ; 4: e48, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28377936

RESUMEN

A 48-year-old man with hepatitis C virus (HCV) cirrhosis complicated by hepatocellular carcinoma underwent liver transplantation. His course was complicated by fever, diarrhea, abdominal pain, and pancytopenia. He developed a diffuse erythematous rash, which progressed to erythroderma. Biopsies of the colon and skin were consistent with acute graft-versus-host disease. Donor-derived lymphocytes were present in the peripheral blood. The patient was treated with corticosteroids and cyclosporine; however, he had minimal response to intensive immunosuppressive therapy. Extracorporeal photopheresis was initiated as a salvage therapy. He had a dramatic response, and his rash, diarrhea, and pancytopenia resolved. He is maintained on minimal immunosuppression 24 months later.

15.
Anticancer Drugs ; 22(4): 311-6, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21301320

RESUMEN

5-Fluorouracil (5-FU) is the most widely used agent for the management of colorectal cancer. Capecitabine is metabolized by three enzymatic actions, the last of which is mediated by thymidine phosphorylase, to produce 5-FU. Given the oral bioavailability of capecitabine as well as in-vitro and in-vivo findings showing higher expression of thymidine phosphorylase in tumor cells and xenografts compared with normal tissue, capecitabine is an evolving candidate in the management of colorectal cancer with antimetabolite-based therapy. An ideal radiosensitizing agent must balance oncological outcomes with adverse effects and feasibility of administration. This discussion addresses the evolving role of 5-FU in the management of rectal cancer in the neoadjuvant setting in combination with ionizing radiation.


Asunto(s)
Antimetabolitos Antineoplásicos/uso terapéutico , Fluorouracilo/uso terapéutico , Fármacos Sensibilizantes a Radiaciones/uso terapéutico , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/radioterapia , Antimetabolitos Antineoplásicos/farmacocinética , Antimetabolitos Antineoplásicos/farmacología , Capecitabina , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacocinética , Desoxicitidina/uso terapéutico , Fluorouracilo/análogos & derivados , Fluorouracilo/farmacocinética , Fluorouracilo/farmacología , Humanos , Terapia Neoadyuvante , Fármacos Sensibilizantes a Radiaciones/farmacocinética , Fármacos Sensibilizantes a Radiaciones/farmacología , Neoplasias del Recto/metabolismo
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...