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1.
Expert Opin Investig Drugs ; 29(2): 125-133, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31899984

RESUMO

Introduction: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and is strongly associated with obesity and insulin resistance. NAFLD refers to a spectrum of disorders ranging from asymptomatic hepatic steatosis (nonalcoholic fatty liver, NAFL) to nonalcoholic steatohepatitis (NASH), which increases the risk of developing more severe forms of liver disease such as progressive fibrosis, cirrhosis, and liver cancer. Currently, there are no food and drug administration (FDA) approved drugs to treat NASH. Pegbelfermin (BMS-986036) is a PEGylated fibroblast growth factor 21 (FGF21) analogue that is under investigation for the treatment of NASH.Areas covered: We reviewed the (pre)clinical pegbelfermin studies and compared these with other studies that assessed FGF21 and FGF21 analogues in the treatment of NASH.Expert opinion: With no FDA approved treatments available for NASH, there is an urgent need for novel therapies. Pegbelfermin is a systemic treatment with pleiotropic effects on various tissues. Short-term adverse effects are limited, but more research is required to study potential long-term safety issues. In a phase 2a trial, pegbelfermin has shown promising improvements in several NASH related outcomes. However, clinical trials demonstrating long-term benefits on hard outcomes such as liver histology, cirrhosis development, or survival are required for further validation.


Assuntos
Fatores de Crescimento de Fibroblastos/análogos & derivados , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Polietilenoglicóis/uso terapêutico , Animais , Progressão da Doença , Drogas em Investigação/efeitos adversos , Drogas em Investigação/farmacologia , Drogas em Investigação/uso terapêutico , Fatores de Crescimento de Fibroblastos/efeitos adversos , Fatores de Crescimento de Fibroblastos/farmacologia , Fatores de Crescimento de Fibroblastos/uso terapêutico , Humanos , Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Obesidade/complicações , Polietilenoglicóis/efeitos adversos , Polietilenoglicóis/farmacologia
2.
Ann Hematol ; 99(2): 331-341, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31853703

RESUMO

G-CSF administration after high-dose chemotherapy and autologous stem cell transplantation (ASCT) has been shown to expedite neutrophil recovery. Several studies comparing filgrastim and pegfilgrastim in the post-ASCT setting concluded that the two are at least equally effective. Lipegfilgrastim (LIP) is a new long-acting, once-per-cycle G-CSF. This multicentric, prospective study aimed to describe the use of LIP in multiple myeloma patients receiving high-dose melphalan and autologous stem cell transplantation (ASCT) and compare LIP with historic controls of patients who received short-acting agent (filgrastim [FIL]). Overall, 125 patients with a median age of 60 years received G-CSF after ASCT (80 patients LIP on day 1 post-ASCT and 45 patients FIL on day 5 post-ASCT). The median duration of grade 4 neutropenia (absolute neutrophil count [ANC] < 0.5 × 10 [9]/L) was 5 days in both LIP and FIL groups, whereas the median number of days to reach ANC ≥ 0.5 × 10 [9]/L was 10% lower in the LIP than in the FIL group (10 vs 11 days), respectively. Male sex was significantly associated with a faster ANC ≥ 0.5 × 10 [9] L response (p = 0.015). The incidence of FN was significantly lower in the LIP than in the FIL group (29% vs 49%, respectively, p = 0.024). The days to discharge after ASCT infusion were greater in patients with FN (p < 0.001). The study indicates that LIP had a shorter time to ANC recovery and is more effective than FIL for the prevention of FN in the ASCT setting.


Assuntos
Filgrastim/administração & dosagem , Melfalan/administração & dosagem , Mieloma Múltiplo/terapia , Polietilenoglicóis/administração & dosagem , Transplante de Células-Tronco , Idoso , Autoenxertos , Feminino , Filgrastim/efeitos adversos , Humanos , Masculino , Melfalan/efeitos adversos , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Polietilenoglicóis/efeitos adversos , Estudos Prospectivos , Fatores Sexuais
3.
J Oncol Pharm Pract ; 26(1): 193-199, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30823860

RESUMO

Pegaspargase, a long acting formulation of L-asparaginase, is an asparagine specific enzyme that selectively kills leukemic cells by depleting plasma asparagine. Pegaspargase is FDA approved for the first-line treatment of adult acute lymphoblastic leukemia and is a critical component of numerous multi-chemotherapeutic regimens. Pegaspargase is associated with well-described toxicities including hypersensitivity reactions, hepatotoxicity, and thrombosis. However, hypertriglyceridemia is a much rarer complication of pegaspargase and has only been described in a limited number of reports. We present a case of severe hypertriglyceridemia after a single dose of pegaspargase. The patient was re-challenged with pegaspargase and again developed hypertriglyceridemia which was complicated by pancreatitis. Here, we summarize published reports and a literature review describing the incidence of pegaspargase-induced hypertriglyceridemia in common acute lymphoblastic leukemia protocols.


Assuntos
Antineoplásicos/efeitos adversos , Asparaginase/efeitos adversos , Hipertrigliceridemia/induzido quimicamente , Polietilenoglicóis/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adulto , Feminino , Humanos
4.
J Oncol Pharm Pract ; 26(1): 74-92, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30917738

RESUMO

The incorporation of L-asparaginase and pegylated asparaginase into pediatric-inspired regimens has conferred a survival advantage in treatment of adults with acute lymphoblastic leukemia. Use of asparaginase products requires careful prevention, monitoring, and management of adverse effects including hypersensitivity, hepatotoxicity, pancreatitis, coagulopathy, and thrombosis. Currently, there is limited published literature to offer guidance on management of these toxicities. At the University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, a standard of practice guideline was created to prevent and manage asparaginase-related adverse events. By sharing our long-term experience with asparaginase products and clinical management of asparaginase-induced toxicities, this article aims to improve patient safety and optimize treatment outcomes.


Assuntos
Antineoplásicos/administração & dosagem , Asparaginase/administração & dosagem , Institutos de Câncer/normas , Gerenciamento Clínico , Monitoramento de Medicamentos/normas , Polietilenoglicóis/administração & dosagem , Guias de Prática Clínica como Assunto/normas , Adulto , Antineoplásicos/efeitos adversos , Asparaginase/efeitos adversos , Pré-Escolar , Relação Dose-Resposta a Droga , Monitoramento de Medicamentos/métodos , Humanos , Polietilenoglicóis/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Trombose/induzido quimicamente , Trombose/epidemiologia , Trombose/prevenção & controle , Resultado do Tratamento
5.
Bone Joint J ; 101-B(12): 1506-1511, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31786997

RESUMO

AIMS: The aim of this study was to compare the osseous reactions elicited by all-suture, polyetheretherketone (PEEK), and two different biodegradable anchors used during rotator cuff repair. PATIENTS AND METHODS: Transosseous-equivalent rotator cuff repair was performed in 73 patients. The patients were divided into two groups, in both of which two different medial-row anchors were used. In group 1, anchor A comprised 30% ß-tricalcium phosphate (TCP) + 70% fast-absorbing poly lactic-co-glycolic acid copolymer (85% polylactic acid enantiomers + 15% polyglycolic acid) and anchor B comprised all-sutures. In group 2, anchor C comprised 23% micro ß-TCP + 77% polylactic acid enantiomers and anchor D comprised PEEK polymer. There were 37 patients in group 1 and 36 patients in group 2. The presence and severity of fluid collection around anchors and healing of the rotator cuff were assessed using MRI scans, approximately one year postoperatively. The severity of the collection was graded as 0 (no perianchor fluid signal), 1 (minimal perianchor fluid), 2 (local collection of fluid), 3 (fluid collection around the whole length of the anchor but of a diameter less than twice the anchor diameter), or 4 (fluid collection around the whole length of the anchor and of a diameter greater than twice the anchor diameter). RESULTS: A perianchor fluid signal was seen in three patients (8.1%) with anchor A, four (10.8%) with anchor B, 15 (41.7%) with anchor C, and 15 (41.7%) with anchor D. The severity of the collection around anchor was grade 2:1:0:0 for anchor A, grade 2:2:0:0 for anchor B, grade 12:2:0:1 for anchor C, and grade 11:3:0:1 for anchor D (grade 1:2:3:4, respectively). The prevalence and severity of fluid formation was not significantly different between anchors A and B, and anchors C and D. However, on intergroup analysis, there were significant differences for the prevalence and severity of fluid formation between anchors in group 1 and group 2. The prevalence of failure to heal was not significant in group 1 (seven, 18.9%) or group 2 (nine, 25.0%). There was no relationship between the presence of perianchor fluid and each type of anchor, and the integrity of the rotator cuff repair, in either group. CONCLUSION: Despite the nonabsorbable nature of all-suture and PEEK anchors, all-suture anchors produced less osseous reaction after rotator cuff repair. In deciding which kind of anchor to use, consideration should be given not only to the strength of the initial fixation, but also to the postoperative biological reaction. Cite this article: Bone Joint J 2019;101-B:1506-1511.


Assuntos
Materiais Biocompatíveis/efeitos adversos , Reação a Corpo Estranho/etiologia , Cetonas/efeitos adversos , Procedimentos Ortopédicos/instrumentação , Polietilenoglicóis/efeitos adversos , Complicações Pós-Operatórias/etiologia , Lesões do Manguito Rotador/cirurgia , Âncoras de Sutura/efeitos adversos , Adulto , Idoso , Feminino , Seguimentos , Reação a Corpo Estranho/diagnóstico por imagem , Reação a Corpo Estranho/epidemiologia , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/epidemiologia , Prevalência , Estudos Prospectivos , Lesões do Manguito Rotador/diagnóstico por imagem , Resultado do Tratamento , Cicatrização
6.
BMC Infect Dis ; 19(1): 848, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31615436

RESUMO

BACKGROUND: Pegylated liposomal doxorubicin plays an important role in the treatment of patients with severe refractory human immunodeficiency virus (HIV)-associated Kaposi sarcoma (KS). High cumulative doses of conventional doxorubicin exceeding 500 mg/m2 are known to cause cardiac toxicity. However, the safe cumulative dose of pegylated liposomal doxorubicin is unclear. CASE PRESENTATION: A 40-year-old Japanese man with HIV infection presented with pain, edema, and multiple skin nodules on both legs which worsened over several months. He was diagnosed with HIV-associated KS. He received long-term pegylated liposomal doxorubicin combined with antiretroviral therapy for advanced, progressive KS. The cumulative dose of pegylated liposomal doxorubicin reached 980 mg/m2. The patient's left ventricular ejection fraction remained unchanged from baseline during treatment. After he died as a result of cachexia and wasting, caused by recurrent sepsis and advanced KS, an autopsy specimen of his heart revealed little or no evidence of histological cardiac damage. We also conducted a literature review focusing on histological changes of the myocardium in patients treated with a cumulative dose of pegylated liposomal doxorubicin exceeding 500 mg/m2. CONCLUSIONS: This case report and literature review suggest that high (> 500 mg/m2) cumulative doses of pegylated liposomal doxorubicin may be used without significant histological/clinical cardiac toxicity in patients with HIV-associated KS.


Assuntos
Doxorrubicina/análogos & derivados , Infecções por HIV/patologia , Sarcoma de Kaposi/tratamento farmacológico , Adulto , Antirretrovirais/uso terapêutico , Relação Dose-Resposta a Droga , Doxorrubicina/efeitos adversos , Doxorrubicina/química , Doxorrubicina/uso terapêutico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Coração/diagnóstico por imagem , Humanos , Masculino , Miocárdio/patologia , Polietilenoglicóis/efeitos adversos , Polietilenoglicóis/química , Polietilenoglicóis/uso terapêutico , Sarcoma de Kaposi/diagnóstico , Sarcoma de Kaposi/etiologia
7.
Cancer Sci ; 110(12): 3754-3760, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31646714

RESUMO

Preoperative or induction chemotherapy with docetaxel, cisplatin, plus 5-fluorouracil (DCF) is a promising regimen for advanced esophageal cancer. However, the DCF regimen is associated with a high risk of severe neutropenia or febrile neutropenia (FN). However, the current guidelines fail to recommend an optimal dosing schedule of pegfilgrastim along with the DCF regimen to prevent FN. In the present study, we assessed the efficacy and safety of giving pegfilgrastim early on day 3 during DCF therapy for esophageal cancer. In this single-arm phase II study, patients with squamous cell carcinoma of the esophagus were recruited. They were treated with the DCF therapy on days 1-5, with pegfilgrastim given on day 3. Primary endpoint was the occurrence of grade 4 neutropenia. Secondary endpoints included the incidence of FN, grade 3 neutropenia, dose delays/reductions, antitumor effect, and safety. Between July 2016 and December 2018, 23 patients were enrolled. The incidence of grade 4 neutropenia was 8.7% (95% confidence interval 1.1%-28.0%). No patient experienced FN. Of the 19 patients who received two cycles of DCF, one required a dose reduction/treatment delay due to hematological toxicity in the second treatment cycle. No serious adverse events, considered relevant to pegfilgrastim, were observed. This is the first prospective study that showed an efficacious dosing schedule of pegfilgrastim for preventing hematological toxicity during DCF therapy. The results might be generalized to other similar regimens where continuous infusions of 5-fluorouracil are used.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Esofágicas/tratamento farmacológico , Filgrastim/uso terapêutico , Polietilenoglicóis/uso terapêutico , Adulto , Idoso , Cisplatino/administração & dosagem , Docetaxel/administração & dosagem , Feminino , Filgrastim/efeitos adversos , Fluoruracila/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Neutropenia/prevenção & controle , Polietilenoglicóis/efeitos adversos , Estudos Prospectivos
8.
Gynecol Oncol ; 155(2): 301-304, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31575390

RESUMO

OBJECTIVE: Pegylated liposomal doxorubicin (PLD) has similar reported clinical efficacy compared with conventional doxorubicin with less cardiotoxicity. The manufacturer of PLD advises that cardiac function should be evaluated with endomyocardial biopsy, echocardiography or multigated radionucleotide scan (MUGA) pre-treatment and during therapy. This study was designed to assess the necessity of pre-treatment cardiac evaluation in patients receiving PLD. METHODS: After IRB approval, a retrospective study of all women with gynecologic cancer who received PLD from 2006 to 2018 was performed. Demographic information, treatment records, cardiac risk factors, and cardiac surveillance testing were examined. Wilcoxon signed rank sum test and logistic regression were used to evaluate the association of cumulative PLD exposure with cardiotoxicity. RESULTS: A total of 235 patients received PLD for gynecologic cancer. Patients received a median of 3 cycles of PLD with a cumulative dosage of 237 mg over a median follow-up time of 24 months. Sixteen patients in the cohort (7%) had no cardiac surveillance at all. Of the remaining patients who underwent cardiac testing, 183 (84%) received MUGA scans and 36 (16%) had echocardiography. Of the 56 patients who had both pre- and post-treatment cardiac testing, there was no significant difference in median ejection fraction (p = 0.17). Three patients developed PLD-associated cardiac toxicity but only one patient had severe manifestations requiring discontinuation of PLD therapy. CONCLUSIONS: Routine cardiac testing before, during or after treatment with PLD may be unnecessary. Cardiac testing may be more appropriate for individual patients for whom the clinical suspicion of PLD-related cardiac toxicity is high.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Doxorrubicina/análogos & derivados , Neoplasias dos Genitais Femininos/tratamento farmacológico , Cardiopatias/induzido quimicamente , Doxorrubicina/efeitos adversos , Substituição de Medicamentos , Ecocardiografia/métodos , Feminino , Cardiopatias/fisiopatologia , Cardiopatias/prevenção & controle , Humanos , Pessoa de Meia-Idade , Imagem Multimodal/métodos , Polietilenoglicóis/efeitos adversos , Angiografia Cintilográfica/métodos , Estudos Retrospectivos , Volume Sistólico/efeitos dos fármacos
9.
Int J Nanomedicine ; 14: 7489-7502, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571860

RESUMO

Background: 3,5,4'-trimethoxy-trans-stilbene (BTM) is a methylated derivative of resveratrol. To improve the pharmaceutical properties of BTM, BTM loaded PEG-PE micelles (BTM@PEG-PE) were fabricated and its anti-cancer efficacy against colon cancer was evaluated. Methods: BTM@PEG-PE micelles were prepared by the solvent evaporation method and were characterized by nuclear magnetic resonance (NMR), size, zeta potential, polymer disperse index (PDI) and transmission electron microscopy (TEM). Cellular uptake, cell viability assay, caspase-3 activity assay and flow cytometry were performed to evaluate the cell internalization and anti-cancer efficacy of BTM@PEG-PE micelles in vitro. Pharmacokinetic profiles of BTM and BTM@PEG-PE micelles were compared and in vivo anti-cancer therapeutic efficacy and safety of BTM@PEG-PE micelles on CT26 xenograft mice were evaluated. Results: BTM was successfully embedded in the core of PEG-PE micelles, with a drug loading capacity of 5.62±0.80%. PEG-PE micelles facilitated BTM entering to the CT26 cells and BTM@PEG-PE micelles exerted enhanced anti-cancer efficacy against CT26 cells. BTM@PEG-PE micelles showed prolonged half-life and increased bioavailability. More importantly, BTM@PEG-PE micelles treatment suppressed tumor growth in tumor-bearing mice and prolonged survival with minimal damage to normal tissues. Conclusion: Altogether, the BTM@PEG-PE micelles might be a promising strategy to enhance the pharmacokinetic and pharmacodynamic potentials of BTM for colon cancer therapy.


Assuntos
Neoplasias do Colo/tratamento farmacológico , Micelas , Fosfatidiletanolaminas/uso terapêutico , Polietilenoglicóis/uso terapêutico , Animais , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Disponibilidade Biológica , Caspase 3/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular , Neoplasias do Colo/patologia , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Endocitose , Feminino , Humanos , Camundongos Endogâmicos BALB C , Fosfatidiletanolaminas/efeitos adversos , Fosfatidiletanolaminas/farmacocinética , Polietilenoglicóis/efeitos adversos , Polietilenoglicóis/farmacocinética , Polímeros/química , Ratos Sprague-Dawley , Resultado do Tratamento
10.
Acta Gastroenterol Belg ; 82(3): 407-415, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31566329

RESUMO

OBJECTIVE: To assess the efficacy adjunction of oral simethicone to polyethylene glycol as bowel preparation agent on cecal intubation rate. METHODS: We searched EMBASE, PubMed and Cochrane library for randomized controlled trials regarding simeticone plus polyethylene glycol as oral drinking agents before gastroscopy,we used the soft RevMan5.3 to perform statistical analysis and stata12.0 for publication bias. RESULTS: 12 randomized trials that met the inclusion criteria were therefore pooled into a meta-analysis, which included a total of 5,112 patients. There were no significant differences on cecal intubation rate in two groups(RR=1.0,95%CI : 0.99-1.01, P=0.93) with moderate level of evidence;Subgroups analysis of 2LPEG+ Simethicone VS 2LPEG(RR =1.0, 95% CI : 0.98,1.01), 2LPEG+ Simethicone VS 4L PEG (RR=1.00, 95% CI : 0.98,1.02), PEG+ Simethicone with bisacodyl vs PEG (RR =1.00, 95% CI : 0.99,1.02), PEG+Simethicone without bisacodyl vs PEG (RR =1.00, 95% CI : 0.98,1.02) showed no difference on cecal intubation rate.There was aslo no significant difference on cecal intubation time.Abdominal bloating incidence was lower in PEG+Simethicone group than that in PEG group (RR=0.53, 95%CI : 0.31, 0.91, P=0.02). The meta-analysis result also showed a better acceptability in PEG+Simethicone group (RR=1.28, 95% CI : 1.01, 1.49, P=0.001). CONCLUSION: Adjunction of oral simethicone to polyethylene glycol as bowel preparation agent dose not improve cecal intubation rate on colonoscopy,but with better gastrointestinal tolerability and acceptability.


Assuntos
Catárticos/administração & dosagem , Colonoscopia/métodos , Polietilenoglicóis/administração & dosagem , Simeticone/administração & dosagem , Catárticos/efeitos adversos , Humanos , Intubação Intratraqueal , Polietilenoglicóis/efeitos adversos , Simeticone/efeitos adversos
11.
Dis Colon Rectum ; 62(12): 1518-1527, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31567921

RESUMO

BACKGROUND: Split-dose bowel preparation is recommended for morning colonoscopy, although a same-day dose regimen is an alternative for afternoon colonoscopy. Same-day preparation for morning colonoscopy has rarely been evaluated. OBJECTIVE: We compared the bowel cleansing efficacy, bowel movement kinetics, safety profile, and patient tolerability of split-dose and same-day preparation using 4-L polyethylene glycol. DESIGN: This was a prospective, randomized, assessor-blinded study. SETTINGS: This study was performed at a tertiary center in Korea. PATIENTS: Study subjects were randomly assigned to the same-day or split-dose groups. For the same-day dose group, 4 L of polyethylene glycol were ingested on the day of colonoscopy starting at 5:00 AM for morning colonoscopy or 7:00 AM for afternoon colonoscopy. In the split-dose group, 2 L of polyethylene glycol were ingested at 9:00 PM the day before colonoscopy, and the remaining 2 L from 7:00 AM for morning colonoscopy or from 10:00 AM for afternoon colonoscopy. Colonoscopy was performed from 10:00 AM. MAIN OUTCOME MEASURES: The efficacy of bowel cleansing was evaluated using the Boston bowel preparation scale. The participants completed questionnaires asking about adverse events, bowel movement kinetics, and tolerability of the preparation before colonoscopy. RESULTS: A total of 339 subjects were included (same-day dose = 172; split dose = 167). One subject in each group did not undergo colonoscopy. The rate of successful cleansing did not differ between the groups (same-day dose = 98.8% vs split dose = 98.2%; p = 0.681). There were no instances of hemodynamic instability or aspiration in either group. Tolerability, including overall satisfaction and willingness to reuse, were comparable between the groups. LIMITATIONS: This was a single-center study. CONCLUSIONS: The bowel cleansing efficacy, safety profile, and tolerability of same-day dosing with polyethylene glycol were comparable with those of split dose. Therefore, same-day dosing with 4 L of polyethylene glycol is a feasible bowel preparation method. See Video Abstract at http://links.lww.com/DCR/B44. COMPARACIÓN DE LA EFICACIA DE LA LIMPIEZA INTESTINAL, LA SEGURIDAD, LA CINÉTICA DEL MOVIMIENTO INTESTINAL Y LA TOLERABILIDAD DEL PACIENTE DE LA PREPARACIÓN INTESTINAL EN EL MISMO DÍA Y EN DOSIS DIVIDIDAS UTILIZANDO 4 L DE POLIETILENGLICOL: UN ESTUDIO PROSPECTIVO ALEATORIZADO: Se recomienda la preparación del intestino en dosis divididas para la colonoscopia de la mañana, aunque un régimen de una sola dosis el mismo día es una alternativa para la colonoscopia en la tarde. La preparación de una sola dosis el mismo día para la colonoscopia matutina rara vez se ha evaluado.Comparamos la eficacia de la limpieza intestinal, la cinética del movimiento intestinal, el perfil de seguridad y la tolerabilidad del paciente de la dosis dividida y la preparación el mismo día utilizando 4 L de polietilenglicol.Este fue un estudio prospectivo, aleatorizado, cegado por el evaluador.Este estudio se realizó en un centro terciario en Corea.Los sujetos del estudio fueron asignados aleatoriamente a el grupo de una dosis en el mismo día o al grupo de dosis dividida. Para el grupo de dosis del mismo día, se ingirieron 4 L de polietilenglicol el día de la colonoscopia a partir de las 5 a.m. para la colonoscopia de la mañana o las 7 a.m. para la colonoscopia de la tarde. En el grupo de dosis dividida, se ingirieron 2 L de polietilenglicol a las 9 p.m. el día anterior a la colonoscopia, y los otros 2 L restantes a partir de las 7 a.m. para la colonoscopia de la mañana o desde las 10 a.m. para la colonoscopia de la tarde. La colonoscopia se realizó a partir de las 10 a.m.La eficacia de la limpieza intestinal se evaluó mediante la escala de preparación intestinal de Boston. Los participantes completaron cuestionarios preguntando sobre los eventos adversos, la cinética del movimiento intestinal y la tolerabilidad de la preparación antes de la colonoscopia.Se incluyeron un total de 339 sujetos (dosis el mismo día, 172; dosis dividida, 167). Un sujeto en cada grupo no se sometió a colonoscopia. La tasa de limpieza exitosa no difirió entre los grupos (dosis el mismo día, 98.8% versus dosis dividida, 98.2%; p = 0.681). No hubo casos de inestabilidad hemodinámica o aspiración en ninguno de los grupos. La tolerabilidad, incluida la satisfacción general y la voluntad de reutilización, fueron comparables entre los grupos.Este fue un estudio de centro único.La eficacia de la limpieza intestinal, el perfil de seguridad y la tolerabilidad de la dosificación en el mismo día con polietilenglicol fueron comparables con los de la dosis dividida. Por lo tanto, la dosificación en el mismo día con 4 L de polietilenglicol es un método factible de preparación intestinal. Vea el video del resumen en http://links.lww.com/DCR/B44.


Assuntos
Catárticos/administração & dosagem , Polietilenoglicóis/administração & dosagem , Idoso , Catárticos/efeitos adversos , Colonoscopia/estatística & dados numéricos , Defecação/efeitos dos fármacos , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Polietilenoglicóis/efeitos adversos , Estudos Prospectivos , Inquéritos e Questionários , Centros de Atenção Terciária , Resultado do Tratamento
12.
BMC Cancer ; 19(1): 792, 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31399079

RESUMO

BACKGROUND: Febrile neutropenia (FN) is a serious complication of myelosuppressive chemotherapy. Clinical practice guidelines recommend routine prophylactic coverage with granulocyte colony-stimulating factor (G-CSF)-such as pegfilgrastim-for most patients receiving chemotherapy with an intermediate to high risk for FN. Patterns of pegfilgrastim prophylaxis during the chemotherapy course and associated FN risks in US clinical practice have not been well characterized. METHODS: A retrospective cohort design and data from two commercial healthcare claims repositories (01/2010-03/2016) and Medicare Claims Research Identifiable Files (01/2007-09/2015) were employed. Study population included patients who had non-metastatic breast cancer or non-Hodgkin's lymphoma and received intermediate/high-risk regimens. Pegfilgrastim prophylaxis use and FN incidence were ascertained in each chemotherapy cycle, and all cycles were pooled for analyses. Adjusted odds ratios for FN were estimated for patients who did versus did not receive pegfilgrastim prophylaxis in that cycle. RESULTS: Study population included 50,778 commercial patients who received 190,622 cycles of chemotherapy and 71,037 Medicare patients who received 271,944 cycles. In cycle 1, 33% of commercial patients and 28% of Medicare patients did not receive pegfilgrastim prophylaxis, and adjusted odds of FN were 2.6 (95% CI 2.3-2.8) and 1.6 (1.5-1.7), respectively, versus those who received pegfilgrastim prophylaxis. In cycle 2, 28% (commercial) and 26% (Medicare) did not receive pegfilgrastim prophylaxis; corresponding adjusted FN odds were comparably elevated (1.9 [1.6-2.2] and 1.6 [1.5-1.8]). Results in subsequent cycles were similar. Across all cycles, 15% of commercial patients and 23% of Medicare patients did not receive pegfilgrastim prophylaxis despite having FN in a prior cycle, and prior FN increased odds of subsequent FN by 2.1-2.4 times. CONCLUSIONS: Notwithstanding clinical practice guidelines, a large minority of patients did not receive G-CSF prophylaxis, and FN incidence was substantially higher among this subset of the population. Appropriate use of pegfilgrastim prophylaxis may reduce patient exposure to this potentially fatal but largely preventable complication of myelosuppressive chemotherapy.


Assuntos
Quimioprevenção , Neutropenia Febril Induzida por Quimioterapia/prevenção & controle , Filgrastim/uso terapêutico , Fármacos Hematológicos/uso terapêutico , Polietilenoglicóis/uso terapêutico , Padrões de Prática Médica , Idoso , Quimioprevenção/métodos , Neutropenia Febril Induzida por Quimioterapia/epidemiologia , Neutropenia Febril Induzida por Quimioterapia/etiologia , Gerenciamento Clínico , Feminino , Filgrastim/administração & dosagem , Filgrastim/efeitos adversos , Fármacos Hematológicos/administração & dosagem , Fármacos Hematológicos/efeitos adversos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/efeitos adversos , Estudos Retrospectivos , Risco , Estados Unidos/epidemiologia
13.
Plast Reconstr Surg ; 144(3): 433e-443e, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31461029

RESUMO

BACKGROUND: Pediatric calvarial reconstruction is challenging because of the unique anatomical and growth considerations in this population. Comparative studies evaluating current cranioplasty materials are lacking. This review addresses the knowledge gap in pediatric cranioplasty outcomes with emphasis on current materials used. METHODS: A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Outcome data comparing fresh bone, banked bone, titanium, poly(methyl methacrylate), and polyetheretherketone were abstracted. RESULTS: Twenty studies met the authors' selection criteria. The mean patient age ranged from 4 to 17.4 years. Autologous cranioplasty was performed in 439 patients, and 201 patients underwent alloplastic reconstruction. Fresh bone grafts and titanium mesh were associated with the lowest infection rates (0.4 percent and 3.3 percent, respectively; p < 0.001), graft failures (2.9 percent and 3.3 percent, respectively; p < 0.001), and surgical-site occurrence rates (8.8 percent and 6.7 percent, respectively; p < 0.001). Banked bone flaps had the highest overall complication rates (51 percent; p < 0.001), bone resorption (39.7 percent; p < 0.001), and failure rates (40.2 percent; p < 0.001), whereas polyetherether ketone had the highest rates of infection (16.1 percent; p < 0.001). CONCLUSIONS: Based on the available evidence to date, fresh bone grafts and titanium mesh demonstrated the lowest surgical-site infection, surgical-site occurrence, and graft failure rates. Banked bone flaps had the highest overall surgical-site complications and graft failures. Pediatric cranioplasty outcomes studies are needed to evaluate current and novel cranioplasty materials.


Assuntos
Transplante Ósseo/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Próteses e Implantes/efeitos adversos , Procedimentos Cirúrgicos Reconstrutivos/efeitos adversos , Adolescente , Fatores Etários , Transplante Ósseo/métodos , Criança , Pré-Escolar , Craniotomia , Humanos , Cetonas/efeitos adversos , Polietilenoglicóis/efeitos adversos , Polimetil Metacrilato/efeitos adversos , Complicações Pós-Operatórias/etiologia , Procedimentos Cirúrgicos Reconstrutivos/instrumentação , Procedimentos Cirúrgicos Reconstrutivos/métodos , Retalhos Cirúrgicos , Titânio/efeitos adversos , Transplante Autólogo/efeitos adversos , Transplante Autólogo/métodos , Resultado do Tratamento
14.
Pediatr Hematol Oncol ; 36(5): 277-286, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31296092

RESUMO

Asparaginase is an important component of multi-agent chemotherapy for the treatment of pediatric acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LLy). Hypersensitivity to the PEGylated form, pegaspargase, is the most common toxicity observed and is ideally addressed by substituting multiple doses of erwinia asparaginase for each subsequent dose of pegaspargase. An international shortage of erwinia asparaginase has limited the therapeutic options for those experiencing pegaspargase hypersensitivity. Here, we report pegaspargase can be safely administered, while maintaining sustained levels of asparaginase activity, to patients who have had a prior hypersensitivity reaction to pegaspargase by using a standard rapid desensitization protocol. Ten patients with prior hypersensitivity reactions to pegaspargase were treated by using a standardized rapid desensitization protocol. Eight patients had therapeutic asparaginase levels between days 4 and 7 of ≥0.05 IU/mL, and seven patients continued to have sustained levels above ≥0.1 IU/mL between days 10 and 14. Based on chemotherapy regimens, five of these patients successfully received more than one dose of pegaspargase utilizing this protocol.


Assuntos
Asparaginase , Proteínas de Bactérias , Dessensibilização Imunológica , Hipersensibilidade a Drogas/prevenção & controle , Polietilenoglicóis , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Adulto , Asparaginase/administração & dosagem , Asparaginase/efeitos adversos , Asparaginase/imunologia , Proteínas de Bactérias/administração & dosagem , Proteínas de Bactérias/efeitos adversos , Proteínas de Bactérias/imunologia , Criança , Pré-Escolar , Hipersensibilidade a Drogas/imunologia , Escherichia coli/enzimologia , Feminino , Humanos , Masculino , Pectobacterium chrysanthemi/enzimologia , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia
16.
Expert Opin Investig Drugs ; 28(8): 667-673, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31353973

RESUMO

Introduction: A PEGylated form of irinotecan, a topoisomerase I inhibitor, is now available in commerce; its safety and efficacy have been tested in platinum resistant/refractory ovarian cancer (PROC) patients. This novel agent is known as Etirinotecan Pegol (EP). EP, like irinotecan, exerts its action through its principal metabolite SN-38. Areas covered: This drug evaluation article focuses on the most recent investigations and clinical progress regarding EP, a long-acting polymer conjugate of irinotecan for the treatment of PROC. Expert opinion: EP provides prolonged and continuous exposure of SN-38 in tumors, when compared to its parent drug irinotecan. Results from phase II studies are comparable in terms of efficacy to other agents of proven use in PROC. A limitation of the use of EP is the schedule-dependent toxicities (mainly diarrhea and dehydration). In the future, EP could be investigated in association with other agents, even in attempts to restore sensitivity to other treatments. PROC remains a very difficult setting and EP might be a valid agent for patients with good performance status that have exhausted therapeutic options. In such a setting, participation in clinical trials is strongly encouraged.


Assuntos
Compostos Heterocíclicos de 4 ou mais Anéis/administração & dosagem , Neoplasias Ovarianas/tratamento farmacológico , Polietilenoglicóis/administração & dosagem , Inibidores da Topoisomerase I/administração & dosagem , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos , Feminino , Compostos Heterocíclicos de 4 ou mais Anéis/efeitos adversos , Humanos , Irinotecano/administração & dosagem , Irinotecano/efeitos adversos , Recidiva Local de Neoplasia , Neoplasias Ovarianas/patologia , Polietilenoglicóis/efeitos adversos , Inibidores da Topoisomerase I/efeitos adversos , Inibidores da Topoisomerase I/farmacologia
17.
BMC Gastroenterol ; 19(1): 79, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31146679

RESUMO

BACKGROUND: Colonoscopy requires colon cleansing. For this, many polyethylene glycol (PEG)-based preparations still require a high preparation-volume intake. Using an increased osmotic load with ascorbate (Asc), five new low-volume PEG-based bowel preparations (LVPEG) were tested for clinical proof of concept. METHODS: This two-part, open-label study examined preparation-volumes of 1-1.25 L and total required fluid volumes of 2-3 L. Part 1, in healthy volunteers, used mean cumulative 24-h stool weight (target > 2750 g) to identify a lead candidate. Part 2 was endoscopist-blinded: patients undergoing screening colonoscopy were randomized before treatment with the selected lead, one of two variants of it, or the control 2 L PEG + Asc. Two primary endpoints were used for proof of concept demonstration: mean 24-h stool weight and bowel cleansing success (Harefield Cleansing Scale). RESULTS: A total of 120 subjects (30 per group) were enrolled/randomized 1:1:1:1 (max 40:60 gender ratio) per completed Part. In Part 1, LVPEG-3 achieved the largest mean stool weight (3399 g: P < 0.0001 vs target) and was selected for Part 2. In Part 2, stool weights exceeded the target, notably for LVPEG-4 (3215 g: P < 0.001), which achieved 100% cleansing success after a total required fluid intake of 2 L. The control achieved 90% cleansing success. Adverse events were few, gastrointestinal in nature and similar between groups. CONCLUSIONS: LVPEG-4 achieved a clinically useful combination of cleansing, safety/tolerability and low consumption volume: 1 L preparation + 1 L required additional fluid. Named NER1006, LVPEG-4 demonstrated clinical proof of concept and warrants further investigation. TRIAL REGISTRATION: October 2012. Identifier: NCT01714466 . EudraCT: 2012-003052-37 The trial was prospectively registered.


Assuntos
Catárticos/administração & dosagem , Colonoscopia , Polietilenoglicóis/administração & dosagem , Adulto , Idoso , Ácido Ascórbico/administração & dosagem , Ácido Ascórbico/efeitos adversos , Catárticos/efeitos adversos , Fezes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/efeitos adversos , Estudo de Prova de Conceito , Método Simples-Cego
18.
Future Oncol ; 15(19): 2211-2225, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31074641

RESUMO

The increasing incidence of breast cancer brain metastases is a major clinical problem with its associated poor prognosis and limited treatment options. The long-acting topoisomerase-1 inhibitor, etirinotecan pegol, was designed to preferentially accumulate in tumor tissue including brain metastases, providing sustained cytotoxic SN38 levels. Motivated by improved survival findings from subgroup analyses from the Phase III BEACON trial, this ongoing randomized, Phase III trial compares etirinotecan pegol to drugs commonly used for advanced breast cancer in patients with stable, treated breast cancer brain metastases who have been previously treated with an anthracycline, taxane and capecitabine. The primary end point is overall survival. Secondary end points include objective response rate, progression-free survival and time to CNS disease progression or recurrence in patients with/without CNS lesions present at study entry. Trial registration number: NCT02915744.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Neoplasias da Mama/tratamento farmacológico , Compostos Heterocíclicos de 4 ou mais Anéis/administração & dosagem , Recidiva Local de Neoplasia/tratamento farmacológico , Polietilenoglicóis/administração & dosagem , Adulto , Idoso , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/secundário , Neoplasias da Mama/patologia , Feminino , Compostos Heterocíclicos de 4 ou mais Anéis/efeitos adversos , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/patologia , Polietilenoglicóis/efeitos adversos , Intervalo Livre de Progressão , Inibidores da Topoisomerase I/administração & dosagem , Inibidores da Topoisomerase I/efeitos adversos
19.
BMC Endocr Disord ; 19(1): 36, 2019 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-30953492

RESUMO

BACKGROUND: This study aimed to investigate the occurrence and risk factors of thyroid dysfunction (TD) in patients with chronic hepatitis C (CHC) infection in Taiwan. METHODS: The data in this study were obtained from the Taiwan National Health Insurance Research (Taiwan NHIR) database between 2001 and 2013. CHC patients treated with pegylated interferon/ribavirin (PEG-IFN/RBV) were enrolled as case patients, and nontreated CHC patients were enrolled as controls and were matched at a control:case ratio of 3:1 by index date, age (± 3 years), and sex. We compared the cumulative incidence of TD between the cohorts at follow-up until 2013. RESULTS: During the study period, 3810 cases and 9393 controls were included in the study. Among the study subjects, 173 (4.5%) case patients and 244 (2.6%) controls were diagnosed with TD during the follow-up period. The types of TD were hypothyroidism (42.9%), hyperthyroidism (31.2%), and thyroiditis (25.9%). Compared to controls during the 13-year follow-up, patients treated with PEG-IFN/RBV had a higher incidence rate of TD (P < 0.0001), as determined using the Kaplan-Meier method. Cox proportional hazards regression analysis showed that female sex (adjusted hazard ratio (HR): 1.49; 95% confidence interval (CI): 1.23-1.75; P < 0.001), treatment with PEG-IFN/RBV (HR: 1.68; 95% CI: 1.38-2.06; P < 0.001), hyperlipidemia (HR: 1.38; 95% CI: 1.12-1.71; P < 0.001), and past history of goiter (HR: 6.40; 95% CI: 5.00-8.18; P < 0.001) were independent predictors for the development of TD. CONCLUSIONS: PEG-IFN/RBV treatment may be an independent risk factor for thyroid dysfunction among patients with hepatitis C virus (HCV) infection. Monitoring thyroid function keenly during PEG-IFN/RBV therapy in patients with chronic HCV infection is recommended for clinicians, especially for female patients and for patients with a history of hyperlipidemia and goiter.


Assuntos
Antivirais/efeitos adversos , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/efeitos adversos , Polietilenoglicóis/efeitos adversos , Ribavirina/efeitos adversos , Doenças da Glândula Tireoide/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Quimioterapia Combinada , Feminino , Seguimentos , Hepatite C Crônica/virologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas Recombinantes/efeitos adversos , Fatores de Risco , Taiwan , Doenças da Glândula Tireoide/induzido quimicamente , Doenças da Glândula Tireoide/epidemiologia , Adulto Jovem
20.
Asia Pac J Clin Oncol ; 15(4): 231-237, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30997742

RESUMO

AIM: Neutropenia is a common side effect of myelosuppressive chemotherapy. Administration of granulocyte colony-stimulating factor is being used for neutropenia prophylaxis, but there are patients who develop neutropenia or febrile neutropenia despite prophylaxis. We attempted to identify potential risk factors for chemotherapy-induced neutropenia in patients with pegfilgrastim prophylaxis. METHODS: This was a single-center, retrospective, observational study of patients with breast cancer or diffuse large B-cell lymphoma. We obtained patients' data from electronic medical records, including baseline demographics and clinical characteristics regarding diseases, treatments and laboratory values. The outcome measures assessed were the incidence of neutropenia and febrile neutropenia. RESULTS: There were a total of 127 patients, including 77 patients with diffuse large B-cell lymphoma (DLBCL) and 50 patients with breast cancer, and we analyzed 722 chemotherapy cycles. We found 88 cases (12.2%) of grade 3 or 4 neutropenia and 39 cases of febrile neutropenia (5.4%). In the univariate analysis, variables associated with both grade 3 or 4 neutropenia and febrile neutropenia were age, cancer type, cancer stage, radiotherapy and platelet count. A multivariate logistic regression model revealed that age, radiotherapy and platelet count were significant factors in severe neutropenia, whereas platelet count was the only statistically significant factor in febrile neutropenia. Platelet counts of less than 150 000/mm3 increased the risk of neutropenia and febrile neutropenia approximately fourfold. In the subgroup analysis of patients with DLBCL, it was found that platelet count was a significant factor for both neutropenia and febrile neutropenia. CONCLUSION: Among cancer patients with pegfilgrastim prophylaxis, advanced age, absence of radiation therapy and low platelet count were independent predictors of neutropenia, and low platelet count was the predictor of febrile neutropenia.


Assuntos
Neoplasias da Mama/complicações , Neoplasias da Mama/tratamento farmacológico , Neutropenia Febril/etiologia , Filgrastim/efeitos adversos , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Linfoma Difuso de Grandes Células B/complicações , Neutropenia/etiologia , Polietilenoglicóis/efeitos adversos , Neoplasias da Mama/patologia , Neutropenia Febril/patologia , Feminino , Filgrastim/farmacologia , Fator Estimulador de Colônias de Granulócitos/farmacologia , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Neutropenia/patologia , Polietilenoglicóis/farmacologia , Estudos Retrospectivos , Fatores de Risco
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