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1.
Ann Oncol ; 32(4): 552-559, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33352201

RESUMO

BACKGROUND: Current treatment options for peripheral T-cell lymphomas (PTCLs) in the relapsed/refractory setting are limited and demonstrate modest response rates with rare achievement of complete response (CR). PATIENTS AND METHODS: This phase I/II study (NCT03052933) investigated the safety and efficacy of copanlisib, a phosphatidylinositol 3-kinase-α/-δ inhibitor, in combination with gemcitabine in 28 patients with relapsed/refractory PTCL. Patients received escalating doses of intravenous copanlisib on days 1, 8, and 15, administered concomitantly with fixed-dose gemcitabine (1000 mg/m2 on days 1 and 8) in 28-day cycles. RESULTS: Dose-limiting toxicity was not observed in the dose-escalation phase and 60 mg copanlisib was selected for phase II evaluation. Twenty-five patients were enrolled in phase II of the study. Frequent grade ≥3 adverse events (AEs) included transient hyperglycemia (57%), neutropenia (45%), thrombocytopenia, (37%), and transient hypertension (19%). However, AEs were manageable, and none were fatal. The overall response rate was 72% with a CR rate of 32%. Median duration of response was 8.2 months, progression-free survival was 6.9 months, and median overall survival was not reached. Combination treatment produced a greater CR rate in patients with angioimmunoblastic T-cell lymphoma than those with PTCL-not otherwise specified (55.6% versus 15.4%, respectively, P = 0.074) and progression-free survival was significantly longer (13.0 versus 5.1 months, respectively, P = 0.024). In an exploratory gene mutation analysis of 24 tumor samples, TSC2 mutation was present in 25% of patients and occurred exclusively in responders. CONCLUSION: The combination of copanlisib and gemcitabine is a safe and effective treatment option in relapsed/refractory PTCLs and represents an important new option for therapy in this rare group of patients.


Assuntos
Linfoma de Células T Periférico , Desoxicitidina/análogos & derivados , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Pirimidinas , Quinazolinas , Resultado do Tratamento , Gencitabina
2.
J Thromb Haemost ; 15(4): 655-661, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28150907

RESUMO

Essentials Data on venous thromboembolism (VTE) after L-asparaginase (L-asp) in Asian lymphoma are scarce. This is a population-based study in Asian patients with lymphoid disease and L-asp-related VTE. The overall incidence of L-asp-associated VTE was similar to reports on Caucasians. This first and largest study in Asians shows that mainly adult patients are at risk of thrombosis. SUMMARY: Background L-asparaginase (L-asp)-associated venous thromboembolism (VTE) is a serious adverse complication associated with acute lymphoblastic leukemia (ALL) and lymphoma treatment. The incidence rate of L-asp-related VTE in Asian cancer patients is not well known. Methods We performed a population-based study between 2009 and 2013 using claim databases, including both diagnostic and medication codes, such as anti-cancer treatment with L-asp and VTE diagnoses from the starting date until 3 months after cessation of L-asp. Results A total of 3286 patients were prescribed L-asp treatment for any type of lymphoid malignancy including ALL and lymphoma; 116 patients (3.5%) experienced VTE. The most common site of thrombosis was the upper extremities (34.5%). Cerebral vein thrombosis (1.7%) occurred in two pediatric patients; 2.4% (43/1795) of pediatric patients and 4.9% (72/1486) of adult patients suffered from VTE, respectively; 2.7% (56/2064) of ALL and 4.9% (59/1217) of lymphoma patients were diagnosed with VTE after L-asp exposure. After univariate analysis, both the diagnosis of lymphoma (vs. ALL) and being an adult patient (vs. pediatric patient) were risk factors for VTE occurrence. However, after multivariate analysis, only age > 18 remained a risk factor for VTE (odds ratio, 1.79; 95% confidence interval, 1.14-2.81). Conclusions This is the first and largest population-based study in Asian patients with lymphoid malignancies treated with L-asp demonstrating that adult patients are at elevated risk of thrombosis after L-asp exposure. The overall incidence of L-asp-related VTE amongst these patients was similar to that in Caucasian populations.


Assuntos
Asparaginase/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Tromboembolia Venosa/induzido quimicamente , Tromboembolia Venosa/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Asparaginase/uso terapêutico , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , Análise Multivariada , República da Coreia , Fatores de Risco , Trombose , Adulto Jovem
3.
Ann Oncol ; 27(6): 1081-1088, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26951627

RESUMO

BACKGROUND: The use of imatinib combined with chemotherapy has demonstrated improved outcome in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL). However, a substantial proportion of patients continue to die as a result of disease progression. PATIENTS AND METHODS: We assessed the minimal residual disease (MRD)-based effect and long-term outcome of first-line incorporation of dasatinib (100 mg once daily) into chemotherapy alternatively for adults with Ph-positive ALL. The primary end point was the major molecular response (MMR) rate by the end of the second dasatinib cycle. Patients with a donor proceeded to allogeneic stem cell transplantation (SCT) as early as possible. MRD monitoring was centrally evaluated by real-time quantitative polymerase chain reaction (4.5-log sensitivity) using bone marrow samples. RESULTS: Fifty-one patients (median age, 46 years) were enrolled and treated with this strategy. After the first dasatinib cycle, 50 patients (98.0%) achieved complete remission (CR). By the end of the second dasatinib cycle, 46 (93.9%) of 49 assessable patients had persistent CR, and 38 (77.6%) had MMR (32.7%) or undetectable MRD (44.9%). On the basis of the MRD kinetics by this time point, the numbers of early-stable, late, and poor molecular responders were 23 (46.9%), 15 (30.7%), and 11 (22.4%), respectively. Thirty-nine patients (76.5%) underwent allogeneic SCT in CR1. After a median follow-up of 54 months, the 4-year cumulative incidence of relapse and disease-free survival (DFS) rate for all patients were 30.0% and 52.0%, respectively, and the corresponding outcomes among those receiving allogeneic SCT in CR1 were 20.5% and 64.1%, respectively. Poor molecular responders had a higher risk of relapse and DFS than those of early-stable molecular responders. CONCLUSION: This dasatinib-based protocol was effective for achieving a good quality molecular response and durable DFS in adults with Ph-positive ALL. TRIAL REGISTRATION: clinicaltrials.gov, NCT01004497.


Assuntos
Dasatinibe/administração & dosagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Neoplasia Residual/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/epidemiologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Masculino , Pessoa de Meia-Idade , Neoplasia Residual/epidemiologia , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Indução de Remissão , Transplante de Células-Tronco , Transplante Homólogo , Resultado do Tratamento
4.
J Thromb Haemost ; 12(7): 1035-43, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24837640

RESUMO

BACKGROUND: Data on the incidence of venous thromboembolism (VTE) following major surgery in Asian populations are limited. METHODS: Using the Korean Health Insurance Review and Assessment Service database, we performed a nationwide population-based epidemiologic study to estimate the incidence of VTE after major orthopedic, cancer, and benign surgeries. VTE cases were identified from all patients undergoing major surgery between 2007 and 2011 using both diagnostic and drug codes as treatment evidence of VTE within 5 weeks of surgery. We also calculated the relative risk of VTE in major orthopedic and cancer surgery compared to benign surgery. RESULTS: The overall rates of postoperative VTE were 1.24%, 0.67%, and 0.05% for major orthopedic, cancer, and benign surgeries, respectively. Hip fracture (1.60%) and colorectal cancer surgeries (1.67%) were associated with the highest rates of VTE, and the rates steadily increased during the study period. Advanced age, female sex, and general anesthesia were independent risk factors for VTE. Patients undergoing surgery for colorectal, pancreatic, ovarian, and esophageal cancer, and major orthopedic surgery had a > 20-fold higher risk of VTE than those undergoing benign surgery. CONCLUSIONS: This is the largest epidemiologic study to investigate the incidence of VTE after major surgery in Asia, demonstrating that the rates of postoperative VTE are lower than in Caucasian populations. This study contributes to a better understanding of the differences in postoperative VTE development between Korean and Caucasian populations; the data also suggest that perioperative prophylactic strategies in Asians should be based on studies of such populations.


Assuntos
Complicações Pós-Operatórias , Tromboembolia Venosa/complicações , Tromboembolia Venosa/epidemiologia , Idoso , Anestesia/efeitos adversos , Bases de Dados Factuais , Feminino , Humanos , Incidência , Seguro Saúde , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/cirurgia , Razão de Chances , Procedimentos Ortopédicos/efeitos adversos , Período Pós-Operatório , República da Coreia , Medição de Risco , Fatores de Risco , Resultado do Tratamento
5.
Bone Marrow Transplant ; 48(3): 425-32, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22941384

RESUMO

The aims of this study were to investigate the outcomes of second salvage auto-SCT and to identify the impacts of a second auto-SCT compared with systemic chemotherapy alone on disease outcome. Data from 48 patients who underwent second auto-SCT were matched to 144 patients (1:3) who received systemic chemotherapy alone from the Korean Myeloma Registry. Groups were matched for nine potential prognostic factors and compared for treatment outcomes. The median age of matching-pairs at relapse was 55.5 years. A total of 156 patients (81%) received vincristine, doxorubicin and dexamethasone induction therapy before the first auto-SCT. Thirty-five patients (73%) in the second auto-SCT group received novel agent-based therapies before the second auto-SCT, and similar proportion in both groups received novel therapies after relapse of front-line auto-SCT. With a median follow-up of 55.3 months, patients who underwent a second auto-SCT had significantly better median OS (55.5 vs 25.4 months, P=0.035). In multivariate analysis for OS, <18 months time to progression after first auto-SCT, International Staging System III and salvage chemotherapy alone were independent predictors for worse OS. The outcomes of second auto-SCT appear to be superior to those of systemic chemotherapy alone. A randomized trial comparing both treatment strategies is required.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/cirurgia , Transplante de Células-Tronco/métodos , Adulto , Idoso , Terapia Combinada , Dexametasona/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Feminino , Humanos , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Terapia de Salvação , Transplante de Células-Tronco/efeitos adversos , Taxa de Sobrevida , Resultado do Tratamento , Vincristina/administração & dosagem
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