RESUMEN
Purpose This is a retrospective, single-center PSM study evaluating the efficacy and safety of chidamide combined with the CHOEP (C-CHOEP) regimen versus the single CHOEP regimen in patients with untreated peripheral T cell lymphomas (PTCL). Patients Patients newly diagnosed with PTCL between January 2015 and June 2021 were recruited, and were 1:1 divided into C-CHOEP and CHOEP groups according to their first-line chemotherapy regimens. The PSM method was used to match the baseline variables to balance the confounding factors. Results A cohort of 33 patients each in the C-CHOEP and CHOEP groups was generated after propensity score-matching (PSM). The complete remission (CR) rates of the C-CHOEP regimen were higher than that of the CHOEP regimen (56.3 vs. 25.8%, p = 0.014), whereas the duration of response of the C-CHOEP group was shorter (median DOR 30 vs. 57 months), resulting in roughly similar progression-free survival (PFS) and (overall survival) OS between the two groups. The responding patients who received chidamide maintenance therapy showed a trend of superior PFS and OS compared with patients who did not receive maintenance therapy. Conclusions The C-CHOEP regimen was well tolerated but failed to show advantages over the CHOEP regimen in patients with untreated PTCL; however, the chidamide maintenance may contribute to a more durable response and stable long-term survival (AU)
Asunto(s)
Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Linfoma de Células T Periférico/tratamiento farmacológico , Linfoma de Células T Periférico/patología , Estudios Retrospectivos , Estudios de Cohortes , Prednisona/administración & dosificación , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Etopósido/administración & dosificación , Estudios de Seguimiento , Puntaje de Propensión , Vincristina/administración & dosificación , Vindesina/administración & dosificaciónRESUMEN
Adult T-cell leukaemia/lymphoma (ATL) patients have a poor prognosis. Here, we investigated the impact of TP53 gene mutations on prognosis of ATL treated in different ways. Among 177 patients, we identified 47 single nucleotide variants or insertion-deletions (SNVs/indels) of the TP53 gene in 37 individuals. TP53 copy number variations (CNVs) were observed in 38 patients. Altogether, 67 of 177 patients harboured TP53 SNVs/indels or TP53 CNVs, and were categorized as having TP53 mutations. In the entire cohort, median survival of patients with and without TP53 mutations was 1·0 and 6·7 years respectively (P < 0·001). After allogeneic haematopoietic stem cell transplantation (HSCT), median survival of patients with (n = 16) and without (n = 29) TP53 mutations was 0·4 years and not reached respectively (P = 0·001). For patients receiving mogamulizumab without allogeneic HSCT, the median survival from the first dose of antibody in patients with TP53 mutations (n = 27) was only 0·9 years, but 5·1 years in those without (n = 42; P < 0·001). Thus, TP53 mutations are associated with unfavourable prognosis of ATL, regardless of treatment strategy. The establishment of alternative modalities to overcome the adverse impact of TP53 mutations in patients with ATL is required.
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Genes p53 , Leucemia-Linfoma de Células T del Adulto/genética , Mutación , Adulto , Anciano , Anciano de 80 o más Años , Aloinjertos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Antígenos CD28/genética , Carboplatino/administración & dosificación , Ciclofosfamida/administración & dosificación , Variaciones en el Número de Copia de ADN , Doxorrubicina/administración & dosificación , Etopósido/administración & dosificación , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Mutación INDEL , Estimación de Kaplan-Meier , Lenalidomida/administración & dosificación , Leucemia-Linfoma de Células T del Adulto/tratamiento farmacológico , Leucemia-Linfoma de Células T del Adulto/mortalidad , Leucemia-Linfoma de Células T del Adulto/terapia , Masculino , Persona de Mediana Edad , Compuestos de Nitrosourea/administración & dosificación , Polimorfismo de Nucleótido Simple , Prednisolona/administración & dosificación , Prednisona/administración & dosificación , Pronóstico , Receptores CCR4/genética , Vincristina/administración & dosificación , Vindesina/administración & dosificaciónRESUMEN
High-dose methotrexate (HD-MTX) at 3 g/m2 is one of the strategies for central nervous system (CNS) prophylaxis in the first-line treatment of aggressive lymphomas, especially in diffuse large B cell lymphoma patients with high-risk CNS-International Prognostic Index. The objective of our study was to retrospectively analyze the safety of 2 cycles of systemic HD-MTX administered as an ambulatory regimen. Between January 2013 and December 2016, 103 patients were carefully selected on 6 criteria, including age < 60, albumin > 34, performance status 0 or 1, normal renal and hepatic functions, good understanding of practical medical guidance, and no loss of weight. Strict procedures of HD-MTX infusion were observed including alkalinization, urine pH monitoring, and leucovorin rescue. Renal and hepatic functions were monitored at days 2 and 7. MTX clearance was not monitored. Toxicities and grades of toxicity were collected according to the NCI-CTCAE (version 4.0). Among the 103 selected patients, 92 (89%) patients successfully completed the planned 2 cycles of HD-MTX on an outpatient basis. Eleven patients completed only 1 cycle, 3 because of lymphoma progression and 8 because of toxicity including 3 grade II hepatotoxicity, 2 grade I/II renal toxicity, 1 grade III neutropenia, 1 active herpetic infection, and 1 grade III ileus reflex. Reported adverse events (AE) included 92 (84%) grade I/II and 18 (16%) grade III/IV. Grade III hepatotoxicity, mostly cytolysis, was the most frequent AE observed with 8 (8%) events. Grade III/IV hematologic toxicities concerned 9 patients with 8 grade III/IV neutropenia and 1 thrombocytopenia. Renal toxicity was rare, mild, and transient, observed with 4 (4%) grade I/II events. Ambulatory administration of HD-MTX at 3 g/m2 without MTX clearance monitoring is safe with strict medical guidance. It requires careful selection of patients before administration, and a renal and hepatic monitoring after the administration.
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Antimetabolitos Antineoplásicos/uso terapéutico , Sistema Nervioso Central/patología , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma no Hodgkin/tratamiento farmacológico , Metotrexato/uso terapéutico , Adolescente , Adulto , Atención Ambulatoria , Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Bleomicina/administración & dosificación , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Enfermedades Hematológicas/inducido químicamente , Humanos , Infusiones Intravenosas , Enfermedades Renales/inducido químicamente , Pruebas de Función Renal , Leucovorina/uso terapéutico , Pruebas de Función Hepática , Linfoma de Células B Grandes Difuso/patología , Linfoma no Hodgkin/patología , Masculino , Metotrexato/administración & dosificación , Metotrexato/efectos adversos , Persona de Mediana Edad , Invasividad Neoplásica , Servicio Ambulatorio en Hospital , Prednisona/administración & dosificación , Estudios Retrospectivos , Rituximab/administración & dosificación , Vincristina/administración & dosificación , Vindesina/administración & dosificación , Adulto JovenRESUMEN
NonHodgkin lymphoma (NHL) is a form of lymphoid malignancy, with diffuse large B cell lymphoma (DLBCL) being the most common NHL isoform. Approximately half of patients with DLBCL are successfully cured via firstline Rituximab, Cyclophosphamide, Epirubicin, Vindesine, Prednisolone (RCHOP) treatment. However, 3040% of patients with DLBCL ultimately suffer from treatmentrefractory or relapsed disease. These patients often suffer from high mortality rates owing to a lack of suitable therapeutic options, and all patients are at a high risk of serious treatmentassociated dosedependent toxicity. As such, it is essential to develop novel treatments for NHL that are less toxic and more efficacious. Oncolytic Vaccinia virus (OVV) has shown promise as a means of treating numerous types of cancer. Gene therapy strategies further enhance OVVbased therapy by improving tumor cell recognition and immune evasion. Beclin1 is an autophagyassociated gene that, when upregulated, induces excess autophagy and cell death. The present study aimed to develop an OVVBeclin1 therapy capable of inducing autophagic tumor cell death. OVVBeclin1 was able to efficiently kill NHL cells and to increase the sensitivity of these cells to RCHOP, thereby decreasing the dosedependent toxic side effects associated with this chemotherapeutic regimen. The combination of OVVBeclin1 and RCHOP also significantly improved tumor growth inhibition and survival in a BALB/c murine model system owing to the synergistic induction of autophagic cell death. Together, these findings suggest that OVVBeclin1 infection can induce significant autophagic cell death in NHL, highlighting this as a novel means of inducing tumor cell death via a mechanism that is distinct from apoptosis and necrosis.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Beclina-1/inmunología , Linfoma de Células B Grandes Difuso/terapia , Viroterapia Oncolítica/métodos , Virus Vaccinia/genética , Anciano , Anciano de 80 o más Años , Animales , Muerte Celular Autofágica/efectos de los fármacos , Muerte Celular Autofágica/inmunología , Beclina-1/genética , Biopsia , Línea Celular Tumoral , Terapia Combinada/métodos , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Ingeniería Genética , Humanos , Linfoma de Células B Grandes Difuso/inmunología , Linfoma de Células B Grandes Difuso/patología , Masculino , Ratones , Persona de Mediana Edad , Virus Oncolíticos/inmunología , Prednisona/administración & dosificación , Rituximab/administración & dosificación , Escape del Tumor/efectos de los fármacos , Virus Vaccinia/inmunología , Vincristina/administración & dosificación , Vindesina/administración & dosificación , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Adult T-cell leukemia/lymphoma (ATL) is a mature T-cell neoplasm and is classified into four subtypes (acute, lymphoma, chronic, and smoldering) according to the Shimoyama classification, established in 1991 through several nationwide surveys based on the clinical diversity of patients diagnosed in 1983-1987 in Japan. Thereafter, no such studies have been conducted. Recently, we conducted a nationwide hospital survey using the method of the 1980s studies, collected baseline data on 996 ATL patients diagnosed in 2010-2011 from 126 hospitals, and reported their unique epidemiological characteristics. Here, we report the follow-up results of registered ATL patients with the goal of evaluating current prognoses and treatment modalities as of 2016-2017. Of 770 evaluable patients, 391 (50.8%) had acute-type, 192 (24.9%) had lymphoma-type, 106 (13.8%) had chronic-type, and 81 (10.5%) had smoldering-type ATL. The initial therapy regimens used for acute/lymphoma-type ATL were vincristine, cyclophosphamide, doxorubicin and prednisone, followed by doxorubicin, ranimustine, and prednisone and then by vindesine, etoposide, carboplatin, and prednisone (VCAP-AMP-VECP)-like in 38.5/41.7% and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-like in 14.6/13.7% of patients. Allogeneic hematopoietic stem cell transplantation was used to treat 15.9/10.4% of acute/lymphoma-type ATL patients. The 4-year survival rates (the median survival time, days) for acute-, lymphoma-, unfavorable chronic-, favorable chronic-, and smoldering-type ATL were 16.8% (252), 19.6% (305), 26.6% (572), 62.1% (1937), and 59.8% (1851), respectively. The 4-year survival rates for acute- and lymphoma-type ATL improved compared with those reported in 1991, but those for chronic- and smoldering-type ATL were not. Further efforts are warranted to develop more efficient therapeutic strategies to improve the prognosis of ATL in Japan.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Leucemia-Linfoma de Células T del Adulto/mortalidad , Leucemia-Linfoma de Células T del Adulto/terapia , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Causas de Muerte , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Encuestas de Atención de la Salud/estadística & datos numéricos , Hospitales/estadística & datos numéricos , Humanos , Japón/epidemiología , Leucemia-Linfoma de Células T del Adulto/sangre , Leucemia-Linfoma de Células T del Adulto/clasificación , Masculino , Persona de Mediana Edad , Compuestos de Nitrosourea/administración & dosificación , Prednisona/administración & dosificación , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Vincristina/administración & dosificación , Vindesina/administración & dosificaciónRESUMEN
OBJECTIVE: To explore the effectiveness and safety of dexamethasone, vindesine, ifosfamide, pegaspargase, and etoposide combination (SVILE regimen) in the treatment of relapsed/refractory extranodal natural killer/T-cell lymphoma, nasal type (R/R-ENKTL). METHODS: This descriptive, retrospective medical chart review assessed data from 20 R/R-ENKTL patients treated with the SVILE regimen between November 2014 and August 2019. Complete response (CR) rate, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) since SVILE treatment were analysed. RESULTS: After receiving 1-5 SVILE regimen chemotherapy cycles (median 2 cycles), patients had ORR and CR rates of 70.0 % and 45.0 %, respectively. Stage â /â ¡ patients had CR rate of 100.0 % and stage â ¢/â £ patients had ORR and CR rates of 60.0 % and 26.7 %, respectively. Three-year PFS and OS rates of the 20 patients were 43.8 % and 54.2 %, respectively. Three-year PFS and OS rates of stage â /â ¡ patients and stage â ¢/â £ patients were 100.0 % vs. 26.7 % and 100.0 % vs. 40.0 % (P ï¼ 0.05), respectively. The PFS and OS of patients who achieved CR after SVILE chemotherapy were significantly better than those of non-CR patients. The main adverse events were reversible haematological toxicity. CONCLUSIONS: The SVILE regimen is a new treatment option that is effective and safe for R/R-ENKTL patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Resistencia a Antineoplásicos/efectos de los fármacos , Linfoma Extranodal de Células NK-T/tratamiento farmacológico , Neoplasias Nasales/tratamiento farmacológico , Adolescente , Adulto , Anciano , Asparaginasa/administración & dosificación , Dexametasona/administración & dosificación , Etopósido/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Ifosfamida/administración & dosificación , Linfoma Extranodal de Células NK-T/patología , Masculino , Persona de Mediana Edad , Neoplasias Nasales/patología , Polietilenglicoles/administración & dosificación , Pronóstico , Estudios Retrospectivos , Terapia Recuperativa , Tasa de Supervivencia , Vindesina/administración & dosificación , Adulto JovenRESUMEN
PURPOSE: To investigate whether coadministration of vindesine is a risk factor for acute kidney injury caused by high-dose methotrexate in patients with hematologic malignancies and identify its mechanism. METHODS: A retrospective analysis was conducted on 211 cycles of HD-MTX therapy in 178 patients with hematological malignancies. Multivariate logistic regression analysis was performed to evaluate whether VDS coadministration was a risk factor for AKI and the inhibitory effect of VDS on MTX was studied in cell models in vitro. RESULTS: The occurrence of AKI was significantly higher in the MTX + VDS group than in the MTX group. Multivariate logistic regression analysis showed that VDS coadministration was an important risk factor for the occurrence of AKI [odds ratio (OR) = 2.62, 95% confidence interval (CI) 1.03-6.66]. After coadministration of VDS, serum MTX concentrations at 24 h, 48 h, and 72 h increased from 0.42 ± 0.46 µmol/L, 0.07 ± 0.01 µmol/L, and 0.03 ± 0.01 µmol/L to 0.98 ± 2.73 µmol/L, 0.18 ± 0.42 µmol/L, and 0.09 ± 0.21 µmol/L (p < 0.05, p < 0.01, and p < 0.01), respectively. Delayed elimination was closely related to AKI (p < 0.001). The transfected cell model results showed that VDS is an inhibitor of the transporters BCRP, MRP2, and OAT1/OAT3. VDS inhibited BCRP and MRP2-mediated transport of MTX with IC50 values of 17.91 µM and 34.73 µM, respectively. CONCLUSIONS: Coadministration of VDS increases HD-MTX-induced AKI in patients with hematologic malignancies, which may be explained by the fact that VDS increases the exposure to and decreases the excretion of MTX by inhibiting OAT1/OAT3, BCRP, and MRP2.
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Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/metabolismo , Lesión Renal Aguda/tratamiento farmacológico , Metotrexato/administración & dosificación , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , Proteínas de Neoplasias/metabolismo , Proteína 1 de Transporte de Anión Orgánico/metabolismo , Transportadores de Anión Orgánico Sodio-Independiente/metabolismo , Vindesina/administración & dosificación , Lesión Renal Aguda/metabolismo , Adolescente , Línea Celular , Línea Celular Tumoral , Femenino , Células HEK293 , Humanos , Masculino , Proteína 2 Asociada a Resistencia a Múltiples Medicamentos , Adulto JovenRESUMEN
WHAT IS KNOWN AND OBJECTIVES: The etoposide, doxorubicin hydrochloride, vincristine sulphate, cyclophosphamide and prednisone (EPOCH) chemotherapy regimen is effective in patients with relapsed or refractory non-Hodgkin's lymphoma. However, vincristine and doxorubicin hydrochloride are relatively toxic, leading to neurovirulence and cardiotoxicity, respectively. In this study, we replaced these drugs with vindesine and epirubicin hydrochloride to reduce the cardiotoxicity and evaluated admixtures containing these drugs along with etoposide in a single infusion bag in vitro. METHODS: The appearance and pH of the admixtures were evaluated, and the number of particles was detected. High-performance liquid chromatography was used to measure the concentration and degradation rates of etoposide, epirubicin hydrochloride and vindesine sulphate in each admixture. RESULTS AND DISCUSSION: No precipitation occurred when mixing clinically relevant concentrations of etoposide, epirubicin hydrochloride and vindesine sulphate in a 0.9% NaCl injection solution. Furthermore, the delta pH of the admixtures was ≤0.12 throughout the experiment, and the number of particles (≥10 and ≥25 µm) in the solutions over the 24 hours post-preparation period met USP standards. Etoposide, epirubicin hydrochloride and vindesine sulphate were retained at >96% of their initial concentrations in the admixtures at 25°C over the course of the experiment. Etoposide, epirubicin hydrochloride and vindesine sulphate are compatible when mixed in a 0.9% NaCl injection solution, and the admixtures are stable for at least 24 hours when stored in infusion bags. WHAT IS NEW AND CONCLUSION: This in vitro analysis indicates the suitability of our novel admixtures containing less toxic drug equivalents in a single infusion bag for clinical application.
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Epirrubicina/administración & dosificación , Etopósido/administración & dosificación , Vindesina/administración & dosificación , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Estabilidad de Medicamentos , Humanos , Bombas de Infusión , Linfoma no Hodgkin/tratamiento farmacológico , Prednisona/administración & dosificación , Vincristina/administración & dosificaciónRESUMEN
Patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) after, or ineligible for, autologous stem cell transplantation (ASCT) have a dismal prognosis. This phase II study evaluated treatment with R-PECC (rituximab, prednisolone, etoposide, chlorambucil, lomustine), every 28 days for 4 cycles in 62 patients, followed by radio-immunotherapy consolidation with 90 Y-ibritumomab tiuxetan in responsive patients. Primary endpoints were failure-free survival (FFS) and incidence of grade ≥3 adverse events from start of 90 Y-ibritumomab tiuxetan. The overall response rate after R-PECC was 50%. Twenty-nine of 31 responsive patients proceeded to 90 Y-ibritumomab tiuxetan. Five out of 15 partial remission patients converted to complete remission after 90 Y-ibritumomab tiuxetan. One-year FFS and overall survival (OS) from start of 90 Y-ibritumomab tiuxetan was 52% (95% confidence interval [CI], 33-68%) and 62% (95% CI, 42-77%), respectively. One-year FFS and OS from start of R-PECC was 28% (95% CI, 17-39%) and 49% (95% CI, 36-61%), respectively. Toxicities of R-PECC and 90 Y-ibritumomab tiuxetan were mainly haematological. In conclusion, for relapsed DLBCL patients the largely oral R-PECC regimen achieves promising response rates, combined with an acceptable safety profile. Consolidation with 90 Y-ibritumomab tiuxetan resulted in long-term response durations in approximately one third of the patients that received it.
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Anticuerpos Monoclonales/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Linfoma de Células B Grandes Difuso/mortalidad , Linfoma de Células B Grandes Difuso/terapia , Rituximab/administración & dosificación , Trasplante de Células Madre , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Autoinjertos , Carmustina/administración & dosificación , Carmustina/efectos adversos , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prednisona/administración & dosificación , Prednisona/efectos adversos , Rituximab/efectos adversos , Tasa de Supervivencia , Vindesina/administración & dosificación , Vindesina/efectos adversosRESUMEN
BACKGROUND: Clear cell sarcoma of the kidney (CCSK) is a rare and aggressive malignant renal tumor. We describe our experience with neoadjuvant transcatheter arterial chemoembolization (TACE) and systematic chemotherapy for the treatment of advanced CCSK in children. METHODS: Between January 2010 and December 2016, seven patients (3 boys and 4 girls; median 2.2â¯years) with advanced CCSK received preoperative TACE of renal artery and systemic chemotherapy. The chemoembolic emulsion for TACE consisted of cisplatin, pirarubicin, vindesine, and iodized oil. Preoperative systemic chemotherapy with vindesine, ifosfamide, and etoposide was administered three weeks after TACE. Nephrectomy was performed three weeks after systemic chemotherapy. After surgery, patients received radiotherapy and postoperative chemotherapy. RESULTS: No cardiotoxicity, renal insufficiency, or hepatic dysfunction was found in any patients. Grade II-III marrow suppression developed in four patients. One patient with tumor progress during neoadjuvant therapy failed to successfully undergo surgery and died. Six patients underwent nephrectomy after neoadjuvant therapy. Median follow-up period was 49.5â¯months (range, 11-83â¯months). Five patients have recurrence-free survival. One patient is still in postoperative chemotherapy after nephrectomy, radiotherapy and thoracoscopic resection of lung metastases. CONCLUSIONS: Neoadjuvant TACE and systemic chemotherapy appeared to be feasible in the treatment of advanced CCSK in this pilot study. THE TYPE OF STUDY: A case series with no comparison group. LEVEL OF EVIDENCE: Level IV.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioembolización Terapéutica/métodos , Neoplasias Renales/terapia , Nefrectomía/métodos , Sarcoma de Células Claras/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Quimioembolización Terapéutica/efectos adversos , Niño , Preescolar , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Terapia Combinada , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Doxorrubicina/análogos & derivados , Femenino , Humanos , Lactante , Aceite Yodado/administración & dosificación , Aceite Yodado/efectos adversos , Riñón/patología , Neoplasias Renales/patología , Masculino , Terapia Neoadyuvante/métodos , Nefrectomía/efectos adversos , Proyectos Piloto , Estudios Retrospectivos , Resultado del Tratamiento , Vindesina/administración & dosificación , Vindesina/efectos adversosRESUMEN
Adult T-cell lymphoma/leukemia (ATL) is a rare T-cell lymphoproliferative neoplasm caused by human T-lymphotrophic virus 1. In its more common, aggressive forms, ATL carries one of the poorest prognoses of the non-Hodgkin lymphomas. The disease has clinical subtypes (ie, acute, lymphoma, chronic, and smoldering forms) defined by the presenting features, and therefore, the clinical course can vary. For the smoldering and lower-risk chronic forms, combinations involving antiviral therapies have shown some success. However, in many patients, the more indolent forms will evolve into the more aggressive subtypes. In the more aggressive acute, lymphoma, and higher-risk chronic forms, the literature supports initial treatment with combination chemotherapy followed by allogeneic transplantation as a potentially curative approach. Recently, mogamulizumab and lenalidomide have shown promise in the treatment of ATL. With better understanding of the molecular drivers of this disease, we hope that the therapeutic landscape will continue to expand.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia-Linfoma de Células T del Adulto/tratamiento farmacológico , Leucemia-Linfoma de Células T del Adulto/patología , Anticuerpos Monoclonales Humanizados/administración & dosificación , Antivirales/administración & dosificación , Carboplatino/administración & dosificación , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Etopósido/uso terapéutico , Humanos , Leucemia-Linfoma de Células T del Adulto/epidemiología , Prednisona/uso terapéutico , Vincristina/uso terapéutico , Vindesina/administración & dosificaciónRESUMEN
BACKGROUND: Long-term outcomes of adults with first-relapsed/refractory (R/R) systemic anaplastic large-cell lymphoma (ALCL) are not definitively established and should be evaluated. PATIENTS AND METHODS: We previously published the long-term outcomes of adults with ALCL initially treated with polychemotherapy in LYmphoma Study Association (LYSA) prospective clinical trials conducted during the pre-brentuximab vedotin era. Herein, we report the long-term outcomes of those patients after the first-relapsed/refractory (R/R) events. RESULTS: Among the 138 (64 (anaplastic lymphoma kinase (ALK(+)) and 74 ALK(-) ALCL) adults initially treated in clinical trials, 40 (14 ALK(+) and 26 ALK(-)) first-R/R ALCL patients and their long-term outcomes were analysed. Median follow-up from the first-R/R events was 12.5 years. For ALK(+) and ALK(-) patients, respectively, median [range] findings were as follows: age at first-R/R event: 35 [19-76] and 61 [34-81] years; time between inclusion in first-line clinical trials and first-R/R events was 6 [1.5-34] and 11.1 [1-67] months (P = 0.36); with median (95% confidence interval) progression-free survival after the first-R/R events: 3.8 (0.7-14.8) and 5.3 (2.4-8.4) months (P = 0.39); and overall survival: 13.6 (0.7-89) and 8.1 (3.3-25) months (P = 0.96). ALCL was the main cause of death. CONCLUSION: Most adults with first-R/R ALCL have poor outcomes, with no significant differences between patients with ALK(+) or ALK(-) disease. These results could be used as reference for the evaluation of new drugs to treat R/R ALCL.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma Anaplásico de Células Grandes/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Bleomicina/administración & dosificación , Brentuximab Vedotina , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Humanos , Inmunoconjugados/administración & dosificación , Masculino , Persona de Mediana Edad , Prednisona/administración & dosificación , Estudios Retrospectivos , Análisis de Supervivencia , Vincristina/administración & dosificación , Vindesina/administración & dosificación , Adulto JovenRESUMEN
Six patients (aged 3-36 mo) with vaginal tumors (rhabdomyosarcoma and endodermal sinus tumor [EST]; n = 3 each) received intraarterial chemotherapy (IAC) and intravenous chemotherapy. Patients underwent internal iliac artery infusion with cisplatin, pirarubicin, and vindesine. Intravenous chemotherapy with vindesine, ifosfamide, and etoposide was administered after 3 weeks. Vaginal tumors disappeared in all patients after 2 or 3 cycles of alternating therapy. Two patients underwent resection of pelvic metastases. Intravenous consolidation chemotherapy was applied. Four patients were disease-free at a median follow-up of 5.8 years. One patient had pelvic recurrence treated with "salvage" therapy with IAC and surgery and was disease-free for 2.5 years.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Tumor del Seno Endodérmico/tratamiento farmacológico , Terapia Neoadyuvante , Rabdomiosarcoma Embrionario/tratamiento farmacológico , Neoplasias Vaginales/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Biopsia , Preescolar , China , Cisplatino/administración & dosificación , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Doxorrubicina/análogos & derivados , Esquema de Medicación , Tumor del Seno Endodérmico/diagnóstico por imagen , Tumor del Seno Endodérmico/secundario , Tumor del Seno Endodérmico/cirugía , Etopósido/administración & dosificación , Femenino , Humanos , Ifosfamida/administración & dosificación , Arteria Ilíaca , Lactante , Infusiones Intraarteriales , Infusiones Intravenosas , Metastasectomía , Neoplasias Pélvicas/tratamiento farmacológico , Neoplasias Pélvicas/secundario , Neoplasias Pélvicas/cirugía , Estudios Retrospectivos , Rabdomiosarcoma Embrionario/diagnóstico por imagen , Rabdomiosarcoma Embrionario/secundario , Rabdomiosarcoma Embrionario/cirugía , Factores de Tiempo , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Neoplasias Vaginales/diagnóstico por imagen , Neoplasias Vaginales/patología , Vindesina/administración & dosificaciónRESUMEN
PURPOSE: Natural killer (NK) cells are well known to be the most important effector cells mediating antibody-dependent cellular cytotoxicity (ADCC) which is an important mechanism of action of antibody drugs. We evaluated the effects of chemotherapy on the cell number and activity of NK cells from patients who received the vincristine-cyclophosphamide-doxorubicin-prednisone (VCAP), doxorubicin-ranimustine-prednisone (AMP), and vindesine-etoposide-carboplatin-prednisone (VECP) (mLSG15) or mLSG15-like (-L) regimen, which is one of the standard of cares for newly diagnosed adult T-cell leukemia-lymphoma (ATL), or the cyclophosphamide-doxorubicin-vincristine-prednisone (CHOP) or CHOP-L regimen which is another standard of care for ATL and peripheral T-cell lymphoma (PTCL). METHODS: The number of lymphocytes and NK cells, and NK cell activity, were assessed using flow cytometry and a (51)Cr release assay, respectively. RESULTS: A total of 26 patients with untreated ATL or PTCL were enrolled, and blood samples from 25 patients were evaluable. NK cell number in ATL decreased after mLSG15/-L treatment, and the degree of decrease in the NK cell number was more prominent just before VECP therapy (Day 15-17 of each cycle) than just before VCAP therapy (Day 1 of each cycle). The NK cell number in ATL after CHOP/-L treatment also decreased. Interestingly, the NK cell activity showed a tendency to increase after the treatment. NK cell number in PTCL did not decrease by CHOP/-L regimen, but the activity was slightly decreased after the treatment. CONCLUSIONS: These results indicate that the effects of chemotherapeutic agents on NK cells vary according to the disease type and intensity of chemotherapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Células Asesinas Naturales/efectos de los fármacos , Leucemia-Linfoma de Células T del Adulto/tratamiento farmacológico , Linfoma de Células T Periférico/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Carboplatino/administración & dosificación , Estudios de Casos y Controles , Ciclofosfamida/administración & dosificación , Ciclofosfamida/farmacología , Ciclofosfamida/uso terapéutico , Doxorrubicina/administración & dosificación , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Etopósido/administración & dosificación , Femenino , Citometría de Flujo , Humanos , Células Asesinas Naturales/metabolismo , Leucemia-Linfoma de Células T del Adulto/patología , Linfoma de Células T Periférico/patología , Masculino , Persona de Mediana Edad , Compuestos de Nitrosourea/administración & dosificación , Prednisona/administración & dosificación , Prednisona/farmacología , Prednisona/uso terapéutico , Vincristina/administración & dosificación , Vincristina/farmacología , Vincristina/uso terapéutico , Vindesina/administración & dosificaciónAsunto(s)
Leucemia-Linfoma de Células T del Adulto/inmunología , Púrpura Trombocitopénica Idiopática/inmunología , Corticoesteroides/administración & dosificación , Aloinjertos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Benzoatos/uso terapéutico , Carboplatino/administración & dosificación , Terapia Combinada , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Etopósido/administración & dosificación , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Hidrazinas/uso terapéutico , Leucemia-Linfoma de Células T del Adulto/complicaciones , Leucemia-Linfoma de Células T del Adulto/tratamiento farmacológico , Leucemia-Linfoma de Células T del Adulto/terapia , Persona de Mediana Edad , Compuestos de Nitrosourea/administración & dosificación , Prednisolona/uso terapéutico , Prednisona/administración & dosificación , Púrpura Trombocitopénica Idiopática/complicaciones , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Pirazoles/uso terapéutico , Remisión Espontánea , Vincristina/administración & dosificación , Vindesina/administración & dosificaciónRESUMEN
OBJECTIVE: We compared the efficacy and clinical outcomes of vindesine and prednisone (VP) and cyclophosphamide, etoposide, vindesine, and prednisone (CEVP) regimens as first-line treatment for multisystem (MS) or multifocal single system (SS-m) adult Langerhans cell histiocytosis (LCH). METHOD: Clinical features, treatment response, and survival of adults with Langerhans cell histiocytosis treated at our center from January 2001 to January 2015 were reviewed retrospectively. RESULTS: Forty-five adult MS or SS-m LCH patients were treated (N=31, CEVP group; N=14, VP group). Both treatment groups had similar gender distributions, patient ages, and extent of disease. The non-active disease rate for both groups was 70.0% and 64.3% (P=0.775), respectively. Median follow-up was 74.9 (range: 2.8-183.6) months and recurrence rates were 71.0% and 78.6% (P=0.593), respectively. The need for second-line therapy was 64.5% and 71.4% (P=0.649), respectively, and mortality rates were 9.7% and 15.4% (P=0.586), respectively. Neutropenia occurred in 48.4% of CEVP-treated patients and 7.1% of VP-treated patients (P=0.008). CONCLUSIONS: CEVP or VP regimens for the treatment of adult SS-m or MS LCH showed similar efficacies, and both regimens were associated with high disease recurrence and the need for second-line therapy.
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Quimioterapia Combinada/métodos , Histiocitosis de Células de Langerhans/tratamiento farmacológico , Adolescente , Adulto , Anciano , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Etopósido/administración & dosificación , Etopósido/efectos adversos , Femenino , Histiocitosis de Células de Langerhans/mortalidad , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Prednisona/administración & dosificación , Prednisona/efectos adversos , Recurrencia , Estudios Retrospectivos , Resultado del Tratamiento , Vindesina/administración & dosificación , Vindesina/efectos adversos , Adulto JovenRESUMEN
OBJECTIVE: The aim of this study was to evaluate a diffusion-weighted magnetic resonance imaging to represent therapeutic response of induction chemoradiation and outcome in patients with non-small cell lung cancer of the superior sulcus. METHODS: Seventeen patients with non-small cell lung cancer of the superior sulcus (median age, 57 years; range, 44-70 years) received induction chemoradiation, followed by surgery. Diffusion-weighted magnetic resonance imaging of the lesion using b values of 0 and 800 s/mm(2) was acquired before treatment and after induction chemoradiation. Changes in tumoral apparent diffusion coefficient were compared with clinical and histopathological response. Cumulative disease-free survival and proportion of surviving were estimated by the Kaplan-Meier method. Survival of diffusion responders and non-responders were compared by log-rank test. RESULTS: A significant correlation was observed between changes of diffusion response after induction chemoradiation and overall survival. Using a defined threshold of percent increase in mean apparent diffusion coefficient, nine out of 17 patients (53%) were classified as diffusion responders and had a mean increase in mean apparent diffusion coefficient of 40.7 ± 11.2%, while eight diffusion non-responding patients (47%) had a mean increase of 11.0 ± 15.5% (P < 0.0001). Significant difference was found in overall survival between diffusion responders and diffusion non-responders (88.9 months versus 20.3 months, P = 0.002). CONCLUSIONS: Diffusion-weighted magnetic resonance imaging represented therapeutic effect and prognosis after induction chemoradiation in patients with non-small cell lung cancer of the superior sulcus.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/terapia , Quimioradioterapia , Imagen de Difusión por Resonancia Magnética , Quimioterapia de Inducción , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Terapia Neoadyuvante/métodos , Toracotomía , Adulto , Anciano , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Cisplatino/administración & dosificación , Supervivencia sin Enfermedad , Fraccionamiento de la Dosis de Radiación , Esquema de Medicación , Femenino , Humanos , Infusiones Intravenosas , Estimación de Kaplan-Meier , Neoplasias Pulmonares/diagnóstico por imagen , Metástasis Linfática/diagnóstico , Masculino , Persona de Mediana Edad , Mitomicina/administración & dosificación , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Pronóstico , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Vindesina/administración & dosificaciónRESUMEN
PURPOSE: The randomized HD2000 trial compared six cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), four escalated plus two standard cycles of BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone), and six cycles of COPP-EBV-CAD (cyclophosphamide, lomustine, vindesine, melphalan, prednisone, epidoxorubicin, vincristine, procarbazine, vinblastine, and bleomycin; CEC) in patients with advanced-stage Hodgkin lymphoma. After a median follow-up of 42 months, patients who received BEACOPP were reported to have experienced better progression-free survival (PFS) but not better overall survival (OS) results than those receiving ABVD. We here report a post hoc analysis of this trial after a median follow-up of 10 years. PATIENTS AND METHODS: Three hundred seven patients were enrolled, 295 of whom were evaluable. At the time of our analysis, the median follow-up for the entire group was 120 months (range, 4 to 169 months). RESULTS: The 10-year PFS results for the ABVD, BEACOPP, and CEC arms were 69%, 75%, and 76%, respectively; corresponding OS results were 85%, 84%, and 86%. Overall, 13 second malignancies were reported: one in the ABVD arm and six each in the BEACOPP and CEC arms. The cumulative risk of developing second malignancies at 10 years was 0.9%, 6.6%, and 6% with ABVD, BEACOPP, and CEC, respectively; the risk with either BEACOPP or CEC was significantly higher than that reported with ABVD (P = .027 and .02, respectively). CONCLUSION: With these mature results, we confirm that patients with advanced Hodgkin lymphoma have similar OS results when treated with ABVD, BEACOPP, or CEC. However, with longer follow-up, we were not able to confirm the superiority of BEACOPP over ABVD in terms of PFS, mainly because of higher mortality rates resulting from second malignancies observed after treatment with BEACOPP and CEC.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/patología , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Bleomicina/administración & dosificación , Ciclofosfamida/administración & dosificación , Dacarbazina/administración & dosificación , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Esquema de Medicación , Epirrubicina/administración & dosificación , Etopósido/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Italia/epidemiología , Estimación de Kaplan-Meier , Lomustina/administración & dosificación , Masculino , Melfalán/administración & dosificación , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Primarias Secundarias/inducido químicamente , Neoplasias Primarias Secundarias/epidemiología , Prednisona/administración & dosificación , Procarbazina/administración & dosificación , Resultado del Tratamiento , Vinblastina/administración & dosificación , Vincristina/administración & dosificación , Vindesina/administración & dosificaciónRESUMEN
BACKGROUND/AIM: The drug combination of procarbazine, lomustine (CCNU) and vincristine (PCV) has been associated with efficacy in oligodendroglial gliomas (OG) when added to radiotherapy as the first line of treatment, despite the important toxicity of this treatment schedule. The aim of the present study was to analyze the tolerance, feasibility and impact of the dose intensity of the PCV regimen on outcome for patients with OG. PATIENTS AND METHODS: We retrospectively reviewed all patients with OG receiving PCV (CCNU=110 mg/m(2)) who were referred to our two Institutions. The total dose and dose adaptation, cycle delay, dose intensity, toxicity and discontinuation of CCNU were analyzed. Impacts on the outcome were evaluated. RESULTS: Between 2007 and 2011, 89 patients received PCV. PCV was administered at relapse in 73% of patients. Only 37% completed six cycles, 13.4% discontinued PCV because of toxicity, the other patients discontinued due to tumor progression. Cycle delay and dose reduction were observed for 62% and 70% patients, respectively. Grade 3 and 4 toxicities were observed in 38% and 8% patients, respectively. Among patients whose disease did not progress under the PCV regimen, discontinuation due to toxicity was significantly correlated to poor progression-free survival (PFS: p=0.023, hazard ratio=2.354) and poor overall survival (OS: p=0.021, hazard ratio=5.093). A factor that negatively impacted PFS was the absence of CCNU dose adaptation (p=0.001), while OS was negatively impacted by the absence of cycle delay (p=0.049) and grade 3/4 toxicities (p=0.045). CONCLUSION: Despite the efficacy of the PCV regimen, significant toxicity is associated with this schedule, which appears to impact its feasibility and efficacy. The optimal PCV schedule with the appropriate CCNU dose-intensity adaptation should be redefined taking into account this finding.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias Encefálicas/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Oligodendroglioma/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Encefálicas/patología , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Supervivencia sin Enfermedad , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Oligodendroglioma/patología , Estudios Retrospectivos , Resultado del Tratamiento , Vindesina/administración & dosificación , Vindesina/efectos adversosRESUMEN
The purpose of this study is to compare the efficacy and safety of Gefitinib versus VMP in combination with three-dimensional conformal radiotherapy (3D-CRT) for multiple brain metastases from non-small cell lung cancer (NSCLC). A total of 73 NSCLC patients with brain metastases from January 2010 to August 2013 were randomly divided into Gefitinib group (37 patients) and VMP chemotherapy group (36 patients). Patients in VMP group received VM-26 100 mg/day by intravenous injection, from day 1 to day 3, cisplatin 25 mg/m2 by intravenous injection, from day 1 to day 3. One cycle was defined as a 21-day therapy duration, with a total of 3 cycles; 2 cycles were used for consolidation. Patients in Gefitinib group received Gefitinib orally. Both groups received 3D-CRT, DT50 Gy/25f/35d from first day and target areas were treated with whole brain radiotherapy. The results of the study are listed below: There was no significant difference in the short-term effects of the two groups (P > 0.05). Median survival time (MST) of Gefitinib was 13.3 months whereas median survival time of VMP group is 12.7 months (P < 0.05). In Gefitinib group, we did not observe any difference of the median survival time between the patients with and without mutation EGFR. Toxicity of Gefitinib groups were characterized by rash, whereas chemotherapy resulted in hematologic toxicities, which included 6 cases of III/IV leucopenia (17.6 %), 3 cases of anemia (8.8 %), and 5 cases of thrombocytopenia (14.7 %), and non-hematological toxicity which was less serious symptoms for gastrointestinal disorders, hair loss, etc. These adverse reactions can be released after symptomatic treatment. No treatment-related deaths occurred. Two patients in VMP group quit due to IV leucopenia. Both oral Gefitinib and systemic VMP chemotherapy in combination with three-dimensional conformal radiotherapy (3D-CRT) could be used to treat brain metastases from non-small cell lung cancer. There were no difference in the short-term effects of the two groups, but long-term effect of Gefitinib group was slightly better than VMP group. Moreover, Gefitinib group showed low toxicity. All together, our finding implicated that Gefitinib is an effective method for patients with brain metastases from NSCLC.