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1.
Zhonghua Nei Ke Za Zhi ; 59(2): 117-123, 2020 Feb 01.
Artigo em Chinês | MEDLINE | ID: mdl-32074684

RESUMO

Objective: To evaluate the efficacy and safety of Oryz-Aspergillus enzyme and pancreatin tablets (Combizym(®)) in the treatment of postprandial distress syndrome (PDS) in the elderly, compared with gastrointestinal motility drugs. Methods: A prospective randomized controlled trial was designed and registered in the China Clinical Trials Registry (ChiCTR-IPR-16008185). The elderly patients with PDS were randomly divided into three groups, including Mosapride group with Mosapride citrate tablets 5 mg 3 times per day for 2 weeks; Combizym(®) group with Combizym tablets 244 mg 3 times per day for 2 weeks; combined treatment group with both drugs and same doses for 2 weeks. The modified Nepean dyspepsia index (NDSI) score, discomfort intensity score and PDS score were calculated on patients before treatment, at the end of first and second week of treatment, as well as 4 weeks after treatment finished, respectively. Adverse effects were evaluated. Results: A total of 323 patients from 16 tertiary hospitals in China were enrolled in this study. Among them, 105 patients were in Mosapride group, 109 in Combizym(®) group and 109 in combined treatment group. There were 148 males (45.8%) and 175 females (54.2%) with median age 71.4±9.0 years (60-100 years). Baseline characteristics of three groups were comparable. After treatment, the NDSI scores in three groups all decreased significantly (P<0.001), while they were similar between groups (P>0.05). The discomfort intensity score and PDS score in three groups showed a significant reduction after treatment (P<0.001), especially in the combined treatment group. Compared with Mosapride group, the scores in Combizym(®) group decreased significantly after one or two weeks [discomfort intensity score: after one week, 4.0(2.5, 8.0) vs. 6.0(3.0, 10.0); after two weeks, 3.0(0.0, 5.0) vs. 4.0(2.0, 6.0); all P<0.05. PDS score: after one week, 6.0(3.0, 9.0) vs. 7.0(3.5, 10.5); after two weeks, 3.0(0.0, 5.0) vs. 4.0(2.0, 7.0); all P<0.05]. The efficacy rate in all patients after first week of treatment was over 15.0%. The efficacy rates after two weeks were 55.2%, 68.8% and 73.4% in Mosapride group, Combizym(®) group and combined treatment group, respectively. After two week treatment, the efficacy rates in Combizym(®) group (P=0.041) and combined group (P=0.006) were higher than that of Mosapride group. The recurrence rate of Mosapride group was 9.5%, which was significantly higher than that of Combizym(®) group (1.8%, P<0.05) and combined treatment group (1.8%, P<0.05). There were no serious adverse effects in the three groups. Conclusions: The efficacy of Oryz-Aspergillus enzyme and pancreatin tablets is comparable with that of Mosapride in elderly PDS patients, with fewer adverse effects and low recurrence rate. Combination regimen indicates better efficacy than that of Oryz-Aspergillus enzyme and pancreatin tablets or Mosapride alone.


Assuntos
Benzamidas/uso terapêutico , Dispepsia/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Motilidade Gastrointestinal/efeitos dos fármacos , Glicosídeo Hidrolases/uso terapêutico , Morfolinas/uso terapêutico , Pancreatina/uso terapêutico , Peptídeo Hidrolases/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Grupo com Ancestrais do Continente Asiático , Benzamidas/efeitos adversos , China , Combinação de Medicamentos , Dispepsia/diagnóstico , Dispepsia/patologia , Feminino , Fármacos Gastrointestinais/efeitos adversos , Glicosídeo Hidrolases/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Morfolinas/efeitos adversos , Pancreatina/efeitos adversos , Peptídeo Hidrolases/efeitos adversos , Período Pós-Prandial , Estudos Prospectivos , Resultado do Tratamento
2.
Medicine (Baltimore) ; 99(2): e18702, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31914075

RESUMO

BACKGROUND/AIMS: Old age is a risk factor of suboptimal bowel preparation. This study aimed to evaluate the efficacy of mosapride citrate with a split dose of polyethylene glycol (PEG) plus ascorbic acid for bowel preparation in elderly patients (aged ≥65 years) before they underwent a colonoscopy. MATERIALS AND METHODS: This prospective investigator-blinded randomized study was conducted from November 2017 to October 2018. The patients were randomly divided into 2 groups, a mosapride group (mosapride citrate with a split-dose of PEG plus ascorbic acid) or a non-mosapride group (a split-dose of PEG plus ascorbic acid alone). Mosapride citrate 15 mg (Gastin CR) was administered once with each split-dose of the bowel preparation. The bowel preparation quality was assessed using the Boston Bowel Preparation Scale (BBPS). RESULTS: A total of 257 patients were finally included and analyzed in our study. The total BBPS score was significantly higher in the mosapride group than in the non-mosapride group (8.53 vs 8.24, P = .033). The BBPS scores of the right colon and mid-colon were 2.75 vs 2.61 (P = .044) and 2.89 vs 2.79 (P = .030), respectively. The rate of adequate bowel preparation (BBPS ≥ 6) was similar in both groups (98.4% vs 98.5%, P = .968), while the rate of excellent bowel preparation (BBPS = 9) was higher in the mosapride group than in the non-mosapride group (73.8% vs 61.1%, P = .029). The total incidence of adverse events during the administration of the bowel cleansing agent, particularly abdominal fullness, was lower in the mosapride group (11.9% vs 30.5%, P < .001). CONCLUSION: The administration of mosapride citrate with a split-dose of PEG plus ascorbic acid in elderly patients showed an increase in bowel preparation efficacy and reduced adverse events, particularly abdominal fullness, during the administration of a bowel cleansing agent.


Assuntos
Ácido Ascórbico/uso terapêutico , Benzamidas/uso terapêutico , Catárticos/uso terapêutico , Colonoscopia/métodos , Morfolinas/uso terapêutico , Polietilenoglicóis/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Ácido Ascórbico/administração & dosagem , Benzamidas/administração & dosagem , Benzamidas/efeitos adversos , Catárticos/administração & dosagem , Catárticos/efeitos adversos , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Morfolinas/administração & dosagem , Morfolinas/efeitos adversos , Cooperação do Paciente , Satisfação do Paciente , Polietilenoglicóis/administração & dosagem , Cuidados Pré-Operatórios , Estudos Prospectivos , Método Simples-Cego
3.
J Cancer Res Clin Oncol ; 146(2): 503-514, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31745703

RESUMO

PURPOSE: Fusion genes can be therapeutically relevant if they result in constitutive activation of oncogenes or repression of tumor suppressors. However, the prevalence and role of fusion genes in female cancers remain largely unexplored. Here, we investigate the fusion gene landscape in triple-negative breast cancer (TNBC) and high-grade serous ovarian cancer (HGSOC), two subtypes of female cancers with high molecular similarity but limited treatment options at present. METHODS: RNA-seq was utilized to identify fusion genes in a cohort of 18 TNBC and HGSOC patients treated with the PI3K inhibitor buparlisib and the PARP inhibitor olaparib in a phase I clinical trial (NCT01623349). Differential gene expression analysis was performed to assess the function of fusion genes in silico. Finally, these findings were correlated with the reported clinical outcomes. RESULTS: A total of 156 fusion genes was detected, whereof 44/156 (28%) events occurred in more than one patient. Low recurrence across samples indicated that the majority of fusion genes were private passenger events. The long non-coding RNA MALAT1 was involved in 97/156 (62%) fusion genes, followed in prevalence by MUC16, FOXP1, WWOX and XIST. Gene expression of FOXP1 was significantly elevated in patients with vs. without FOXP1 fusion (P= 0.02). From a clinical perspective, FOXP1 fusions were associated with a favorable overall survival. CONCLUSIONS: In summary, this study provides the first characterization of fusion genes in a cohort of TNBC and HGSOC patients. An improved mechanistic understanding of fusion genes will support the future identification of innovative therapeutic approaches for these challenging diseases.


Assuntos
Cistadenocarcinoma Seroso/genética , Fusão Gênica , Neoplasias Ovarianas/genética , Neoplasias de Mama Triplo Negativas/genética , Adulto , Idoso , Aminopiridinas/administração & dosagem , Aminopiridinas/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ensaios Clínicos Fase I como Assunto , Cistadenocarcinoma Seroso/tratamento farmacológico , Feminino , Fatores de Transcrição Forkhead/genética , Perfilação da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Morfolinas/administração & dosagem , Morfolinas/efeitos adversos , Neoplasias Ovarianas/tratamento farmacológico , Ftalazinas/administração & dosagem , Ftalazinas/efeitos adversos , Piperazinas/administração & dosagem , Piperazinas/efeitos adversos , Proteínas Repressoras/genética , Neoplasias de Mama Triplo Negativas/tratamento farmacológico
4.
Medicine (Baltimore) ; 98(44): e17614, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689768

RESUMO

INTRODUCTION: The efficacy of neoadjuvant buparlisib for breast cancer remains controversial. We conduct a systematic review and meta-analysis to explore the influence of neoadjuvant buparlisib versus placebo for breast cancer. METHODS: We search PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through May 2019 for randomized controlled trials (RCTs) assessing the efficacy and safety of neoadjuvant buparlisib versus placebo for breast cancer. This meta-analysis is performed using the random-effect model. RESULTS: Four RCTs are included in the meta-analysis. Overall, compared with control group for breast cancer, neoadjuvant buparlisib can substantially reduce progressive disease (risk ratios [RR] = 0.66; 95% confidence interval [CI] = 0.52-0.82; P = .0003) and improve stable disease (RR = 1.29; 95% CI = 1.02-1.64; P = .04), but has no notable influence on overall response rate (RR = 1.32; 95% CI = 0.84-2.06; P = .22), clinical benefit rate (RR = 1.06; 95% CI = 0.79-1.43; P = .69). Neoadjuvant buparlisib results in the increase in adverse grade 3/4 adverse events including increased alanine aminotransferase (ALT) (RR = 11.87; 95% CI = 5.65-24.90; P < .00001), increased aspartate aminotransferase (AST) (RR = 6.50; 95% CI = 4.14-10.21; P < .00001) and hyperglycaemia (RR = 36.65; 95% CI = 10.44-128.68; P < .00001), as well as serious adverse events (RR = 1.47; 95% CI = 1.23-1.76; P < .0001) compared to placebo. Deaths is found to be similar between two groups (RR = 0.88; 95% CI = 0.75-1.04; P = .13). CONCLUSIONS: Neoadjuvant buparlisib may provide some efficacy for breast cancer, but leads to the increase in serious adverse events.


Assuntos
Aminopiridinas/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Morfolinas/uso terapêutico , Fosfatidilinositol 3-Quinase/antagonistas & inibidores , Aminopiridinas/administração & dosagem , Aminopiridinas/efeitos adversos , Neoplasias da Mama/patologia , Humanos , Morfolinas/administração & dosagem , Morfolinas/efeitos adversos , Terapia Neoadjuvante , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptor ErbB-2/biossíntese
5.
Hematol Oncol ; 37(4): 352-359, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31385336

RESUMO

Patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are unfit for or relapsed postautologous stem-cell transplantation have poor outcomes. Historically, mTORC1 inhibitors have produced responses in approximately 30% of patients in this setting. mTORC1 inhibitor efficacy may be limited by resistance mechanisms including AKT activation by mTORC2. To date, dual mTORC1/2 inhibitors targeting both the TORC1 and TORC2 complexes have not been investigated in DLBCL. This phase II trial investigated the oral dual mTORC1/2 inhibitor vistusertib in an intermittent dosing schedule of 125 mg b.d. for 2 days per week. Thirty patients received vistusertib and six received vistusertib-rituximab for up to six cycles (28-day cycles). Two partial responses were achieved on monotherapy. Durations of response were 57 and 62 days, respectively, for these patients. 19% had stable disease within six cycles. In the monotherapy arm, the median progression-free survival was1.69 (95% confidence interval [CI] 1.61-2.14) months and median overall survival was 6.58 (95% CI 3.81-not reached) months, respectively. The median duration of response or stable disease across the trial duration was 153 days (95% CI 112-not reached). Tumour responses according to positron emission tomography/computed tomography versus computed tomography were concordant. There were no differences noted in tumour volume response according to cell of origin by either gene expression profiling or immunohistochemistry. Vistusertib ± rituximab was well tolerated; across 36 patients 86% of adverse events were grade (G) 1-2. Common vistusertib-related adverse events were similar to those described with mTORC1 inhibitors: nausea (47% G1-2), diarrhoea (27% G1-2, 6% G3), fatigue (30% G1-2, 3% G3), mucositis (25% G1-2, 6% G3), vomiting (17% G1-2), and dyspepsia (14% G1-2). Dual mTORC1/2 inhibitors do not clearly confer an advantage over mTORC1 inhibitors in relapsed or refractory DLBCL. Potential resistance mechanisms are discussed within.


Assuntos
Antineoplásicos/efeitos adversos , Benzamidas/efeitos adversos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Alvo Mecanístico do Complexo 1 de Rapamicina/antagonistas & inibidores , Alvo Mecanístico do Complexo 2 de Rapamicina/antagonistas & inibidores , Terapia de Alvo Molecular , Morfolinas/efeitos adversos , Proteínas de Neoplasias/antagonistas & inibidores , Inibidores de Proteínas Quinases/efeitos adversos , Pirimidinas/efeitos adversos , Terapia de Salvação , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Subpopulações de Linfócitos B/patologia , Benzamidas/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Feminino , Gastroenteropatias/induzido quimicamente , Humanos , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Morfolinas/uso terapêutico , Células-Tronco Neoplásicas/patologia , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Rituximab/administração & dosagem , Rituximab/efeitos adversos
6.
Expert Opin Drug Saf ; 18(7): 553-562, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31159599

RESUMO

Introduction: Activation of phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathways occurs in 70% of breast cancer, including PIK3CA activating mutations, PTEN loss and AKT mutation. It is associated with poor prognosis and resistance to anti-HER2 and endocrine therapy. PI3K inhibitors are promising anticancer targets that can reverse resistance to these therapies. Buparlisib (BKM-120) is an orally active pan-PI3K inhibitor evaluated in different solid tumors as monotherapy or in combination. Areas covered: This article reviews preclinical data, clinical studies that have evaluated the efficacy and safety profiles of buparlisib as a monotherapy or in combination with targeted therapy (including endocrine and anti-HER2 therapy) or cytotoxics. The authors cover completed and ongoing studies to evaluate the benefit vs risk profile of buparlisib. Expert opinion: Targeting PI3K showed efficacy in BC. Buparlisib, a pan PI3K inhibitor, presents manageable but not negligible toxicity with an activity/toxicity ratio in favor of the use of emerging second generation, α-selective PI3K inhibitors for ongoing and future trials.


Assuntos
Aminopiridinas/administração & dosagem , Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Morfolinas/administração & dosagem , Administração Oral , Aminopiridinas/efeitos adversos , Aminopiridinas/farmacologia , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Feminino , Humanos , Terapia de Alvo Molecular , Morfolinas/efeitos adversos , Morfolinas/farmacologia , Mutação
7.
Expert Opin Drug Metab Toxicol ; 15(5): 407-415, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30991855

RESUMO

INTRODUCTION: About 40% of patients with epilepsy are associated with drug-resistant seizures, therefore there has been a continuous search for novel treatment approaches. In experimental studies, natural and synthetic cannabimimetic compounds alone or combined with antiepileptic drugs (AEDs) have been extensively studied and cannabidiol, a naturally occurring compound, has been involved in a number of clinical trials. Areas covered: The authors have performed a literature search (PubMed database up to December 2018) for studies evaluating interactions between AEDs and cannabinoid receptor ligands in experimental models of seizures. Clinical data relate to the add-on treatment with cannabidiol. Expert opinion: WIN55,212-2 mesylate (WIN, a non-selective agonist of CB1 and CB2 receptors) significantly potentiated the anticonvulsant activity of various  AEDs in mice. Profound neurotoxic effects accompanied combinations of WIN with conventional AEDs. Among conventional and newer AEDs, ACEA (a selective CB1 receptor agonist) enhanced the protective action of phenobarbital and levetiracetam without accompanying adverse effects or pharmacokinetic interactions. Cannabidiol proved effective in clinical trials, reducing seizure frequency and the most frequently observed adverse effects were diarrhea, somnolence, and poor appetite. The retention rate was within 14-24% (12-14 weeks - 1 year) but it reached the level of 35% after 2 years.


Assuntos
Anticonvulsivantes/administração & dosagem , Canabinoides/administração & dosagem , Epilepsia/tratamento farmacológico , Animais , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/farmacologia , Benzoxazinas/administração & dosagem , Benzoxazinas/efeitos adversos , Benzoxazinas/farmacologia , Canabinoides/efeitos adversos , Canabinoides/farmacologia , Modelos Animais de Doenças , Interações Medicamentosas , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Humanos , Camundongos , Morfolinas/administração & dosagem , Morfolinas/efeitos adversos , Morfolinas/farmacologia , Naftalenos/administração & dosagem , Naftalenos/efeitos adversos , Naftalenos/farmacologia
8.
PLoS One ; 14(1): e0211346, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30703155

RESUMO

Nicotine and cannabis use during adolescence has the potential to induce long lasting changes on affective and cognitive function. Here, we examined whether adolescent exposure to nicotine, the cannabinoid agonist WIN55-212,2 (WIN), or co-exposure to both would alter operant learning, locomotion, and anxiety- and reward-related behaviors in male and female mice during adulthood. Males exposed to a moderate dose of WIN (2 mg/kg) or co-exposed to nicotine and the moderate dose of WIN exhibited decreased anxiety-associated behaviors and increased cognitive flexibility, but did not differ in operant learning or generalized locomotion. In contrast, differences were not found among the females in these measures at the moderate WIN dose or in both sexes with exposure to a low WIN dose (0.2 mg/kg). Furthermore, a sex-dependent dissociative effect was found in natural reward consumption. Males exposed to the moderate dose of WIN or co-exposed to nicotine and the moderate dose of WIN demonstrated increased sucrose consumption. In contrast, females exposed to the moderate dose of WIN exhibited a decrease in sucrose consumption, which was ameliorated with co-administration of nicotine. Together, these novel findings demonstrate that adolescent exposure to cannabinoids in the presence or absence of nicotine results in altered affective and reward-related behaviors during adulthood.


Assuntos
Ansiedade/tratamento farmacológico , Benzoxazinas/efeitos adversos , Morfolinas/efeitos adversos , Naftalenos/efeitos adversos , Nicotina/efeitos adversos , Animais , Condicionamento Operante/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Humanos , Locomoção/efeitos dos fármacos , Masculino , Camundongos , Recompensa , Caracteres Sexuais , Sacarose/metabolismo
9.
J Clin Oncol ; 37(9): 741-750, 2019 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-30715997

RESUMO

PURPOSE: Phosphatidylinositol 3-kinase (PI3K) signaling is highly active in glioblastomas. We assessed pharmacokinetics, pharmacodynamics, and efficacy of the pan-PI3K inhibitor buparlisib in patients with recurrent glioblastoma with PI3K pathway activation. METHODS: This study was a multicenter, open-label, multi-arm, phase II trial in patients with PI3K pathway-activated glioblastoma at first or second recurrence. In cohort 1, patients scheduled for re-operation after progression received buparlisib for 7 to 13 days before surgery to evaluate brain penetration and modulation of the PI3K pathway in resected tumor tissue. In cohort 2, patients not eligible for re-operation received buparlisib until progression or unacceptable toxicity. Once daily oral buparlisib 100 mg was administered on a continuous 28-day schedule. Primary end points were PI3K pathway inhibition in tumor tissue and buparlisib pharmacokinetics in cohort 1 and 6-month progression-free survival (PFS6) in cohort 2. RESULTS: Sixty-five patients were treated (cohort 1, n = 15; cohort 2, n = 50). In cohort 1, reduction of phosphorylated AKTS473 immunohistochemistry score was achieved in six (42.8%) of 14 patients, but effects on phosphoribosomal protein S6S235/236 and proliferation were not significant. Tumor-to-plasma drug level was 1.0. In cohort 2, four (8%) of 50 patients reached 6-month PFS6, and the median PFS was 1.7 months (95% CI, 1.4 to 1.8 months). The most common grade 3 or greater adverse events related to treatment were lipase elevation (n = 7 [10.8%]), fatigue (n = 4 [6.2%]), hyperglycemia (n = 3 [4.6%]), and elevated ALT (n = 3 [4.6%]). CONCLUSION: Buparlisib had minimal single-agent efficacy in patients with PI3K-activated recurrent glioblastoma. Although buparlisib achieved significant brain penetration, the lack of clinical efficacy was explained by incomplete blockade of the PI3K pathway in tumor tissue. Integrative results suggest that additional study of PI3K inhibitors that achieve more-complete pathway inhibition may still be warranted.


Assuntos
Aminopiridinas/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Morfolinas/uso terapêutico , Terapia Neoadjuvante , Recidiva Local de Neoplasia , Fosfatidilinositol 3-Quinase/metabolismo , /uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Aminopiridinas/efeitos adversos , Aminopiridinas/farmacocinética , Antineoplásicos/efeitos adversos , Neoplasias Encefálicas/enzimologia , Neoplasias Encefálicas/patologia , Quimioterapia Adjuvante , Progressão da Doença , Ativação Enzimática , Feminino , Glioblastoma/enzimologia , Glioblastoma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Morfolinas/efeitos adversos , Morfolinas/farmacocinética , Terapia Neoadjuvante/efeitos adversos , /farmacocinética , Intervalo Livre de Progressão , Fatores de Tempo
10.
Pediatr Int ; 61(3): 235-239, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30615239

RESUMO

BACKGROUND: Single-dose i.v. fosaprepitant has been approved as an alternative to 3 day oral aprepitant, a neurokinin-1 receptor antagonist, and improves prevention of chemotherapy-induced nausea and vomiting (CINV). Because fosaprepitant has shown similar efficacy to aprepitant in adult patients only, this study compared the efficacy and safety of aprepitant and fosaprepitant in pediatric patients. METHODS: Children younger than 18 years who received aprepitant or fosaprepitant to manage CINV between January 2015 and March 2018 at the National Cancer Center Hospital (Tokyo) were recruited to this study. The primary endpoint was complete response (CR; no vomiting/rescue medication) between 0 and 120 h after the start of chemotherapy. Secondary endpoints were safety based on the frequency of severe adverse events, and evaluation of patient characteristics as risk factors (effect of age and sex). RESULTS: A total of 125 chemotherapy cycles were evaluated. In the aprepitant group, CR was observed in 36 of 80 treatment cycles (45.0%), whereas in the fosaprepitant group, it was observed in 19 of 45 cycles (42.2%; P = 0.852). No treatment-related severe adverse events were observed in either group. The number of non-CR was greater than that of CR in patients aged 6-14 years. The difference in CR rate between male and female patients was not statistically significant (47.1% vs 40.0%, respectively; P = 0.471). CONCLUSIONS: Aprepitant and fosaprepitant were safely used and may be equally useful for pediatric patients receiving highly emetogenic chemotherapy. CR rate may be associated with patient age.


Assuntos
Antieméticos/uso terapêutico , Antineoplásicos/efeitos adversos , Aprepitanto/uso terapêutico , Morfolinas/uso terapêutico , Vômito/tratamento farmacológico , Adolescente , Antieméticos/efeitos adversos , Aprepitanto/efeitos adversos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Morfolinas/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Tóquio , Resultado do Tratamento , Vômito/induzido quimicamente
11.
Medicine (Baltimore) ; 98(2): e14064, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30633208

RESUMO

BACKGROUND: There are many trials on the combination of Pinaverium bromide (PB) and Flupentixol-melitracen (FM) in the treatment of diarrhea-type irritable bowel syndrome (IBS-D), but the sample sizes are small, and the research conclusions are inconsistent. Thus, a meta-analysis was performed, aiming to evaluate the efficacy and safety of this combination therapy in patients with IBS-D. METHODS: A systematic literature search was conducted in 7 databases covering the period up to July 2018 to identify randomized controlled trials (RCTs) of PB combined with FM versus PB alone for IBS-D. The primary outcome was the total symptom relief rate. The other outcomes were the adverse events rate, HAMA/SAS score, and HAMD/SDS score. The methodological quality of the RCTs was assessed independently using 6 criteria according to the Cochrane Collaboration. All data were analyzed using Review Manager 5.3. RESULTS: Fifteen RCTs with 1487 participants were identified from 2005 to 2018. Compared with PB alone, 15 RCTs showed significant effects of PB plus FM in terms of improved symptom relief in patients with IBS-D (n = 1487, OR = 5.17, 95%CI, 3.79-7.07, P < .00001). Eleven RCTs reported adverse effects in both the PB plus FM and PB groups, there was no statistically significant difference in the adverse events rate between the 2 groups (n = 1207, OR = 2.91, 95%CI, 0.91-9.28, P = 0.07). Two RCTs and 3 RCTs reported HAMA and HAMD scores respectively, and 3 RCTs reported both SAS and SDS scores. After treatment, the above scores in the PB plus FM group were significantly lower than the PB group (all P < .01). However, the trials were deemed to have a medium risk of bias. CONCLUSIONS: The efficacy of PB combined with FM is superior to PB alone in the treatment of IBS-D, and it is safe for clinical use. However, the conclusions still need to be verified by conducting more large-scale and high-quality RCTs.


Assuntos
Antracenos/uso terapêutico , Flupentixol/uso terapêutico , Fármacos Gastrointestinais/uso terapêutico , Síndrome do Intestino Irritável/tratamento farmacológico , Morfolinas/uso terapêutico , Antracenos/efeitos adversos , Diarreia/tratamento farmacológico , Combinação de Medicamentos , Quimioterapia Combinada , Flupentixol/efeitos adversos , Fármacos Gastrointestinais/efeitos adversos , Humanos , Morfolinas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto
12.
Future Oncol ; 15(3): 241-255, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30304952

RESUMO

Chemotherapy-induced nausea and vomiting (CINV) may occur during the acute (0-24 h) or delayed (25-120 h) phase following chemotherapy administration. The addition of a neurokinin 1 receptor antagonist to antiemetic regimens containing a 5-hydroxytryptamine type 3 receptor antagonist and dexamethasone has resulted in improved CINV prophylaxis. Due to numerous adverse events and hypersensitivity reactions associated with fosaprepitant, a commonly used neurokinin 1 receptor antagonist, there remains an unmet need for better-tolerated formulations. HTX-019, the US FDA-approved polysorbate 80- and synthetic surfactant-free aprepitant injectable emulsion, is bioequivalent to and better tolerated (fewer treatment-emergent adverse events) than fosaprepitant. HTX-019 represents a valuable alternative to fosaprepitant for CINV prophylaxis.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/tratamento farmacológico , Náusea/tratamento farmacológico , Antagonistas do Receptor de Neuroquinina-1/administração & dosagem , Polissorbatos/administração & dosagem , Vômito/tratamento farmacológico , Aprepitanto/administração & dosagem , Ensaios Clínicos como Assunto , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Humanos , Quimioterapia de Indução/efeitos adversos , Morfolinas/efeitos adversos , Náusea/induzido quimicamente , Receptores da Neurocinina-1/genética , Vômito/induzido quimicamente
13.
Xenobiotica ; 49(5): 584-590, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-29790816

RESUMO

The pharmacokinetics of TAK-272 (SCO-272), an orally active renin inhibitor, was investigated in rats with subcutaneously injected turpentine oil, which was an inflammation animal model. Following intravenous administration of TAK-272 to the turpentine-treated rats, the systemic clearance and volume of distribution decreased with the elevated plasma α1-acid glycoprotein (AGP) levels. The elevated plasma AGP levels were negatively correlated with the plasma unbound fraction of TAK-272 in the rats. Although the AUCs of total TAK-272 in the turpentine-treated rats were higher than those in the control rats after intravenous and oral administration, those of unbound TAK-272, which seem to directly contribute to the pharmacological effect and safety, were nearly equal between the turpentine-treated and control rats in the respective dose routes. TAK-272 has been shown to primarily bind to AGP in the human plasma. These results strongly suggested that the pharmacokinetic of TAK-272 in humans would also be affected by the variation in the plasma AGP levels and should be discussed with not only the total concentrations but also the unbound concentrations in the clinical trial for patients with elevated plasma AGP levels.


Assuntos
Benzimidazóis/farmacologia , Benzimidazóis/farmacocinética , Morfolinas/farmacologia , Morfolinas/farmacocinética , Orosomucoide/metabolismo , Piperidinas/farmacologia , Piperidinas/farmacocinética , Renina/antagonistas & inibidores , Administração Oral , Animais , Benzimidazóis/efeitos adversos , Masculino , Morfolinas/efeitos adversos , Piperidinas/efeitos adversos , Ratos , Ratos Sprague-Dawley , Terebintina/farmacocinética , Terebintina/farmacologia
14.
J Oncol Pharm Pract ; 25(5): 1053-1057, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29651918

RESUMO

PURPOSE: Fosaprepitant (Emend®) is an antiemetic frequently used for the prevention of chemotherapy-induced nausea and vomiting. We previously documented an overall 28.7% incidence of infusion-site reactions in patients receiving fosaprepitant via peripheral venous access. These data resulted in a practice change within our institution; fosaprepitant is administered in more dilute concentrations over 30 min to prevent these adverse events. This retrospective study explored the impact of this practice change on the incidence of infusion-site reactions. METHODS: Medical records of patients with cancer receiving intravenous fosaprepitant through a peripheral intravenous line were reviewed. The primary objective of this study was to compare the incidence of infusion-site reactions before the practice change to the incidence after the practice change. Data collection included demographics, fosaprepitant infusion information, and grading of reactions. RESULTS: Between September 2013 and December of 2013, charts of 122 patients receiving intravenous fosaprepitant through a peripheral line at the The Arthur G. James Cancer Hospital at The Ohio State University were reviewed. We found a 5.74% incidence of infusion-site reactions which is significantly lower than the prechange incidence of 28.7% (p < 0.001). CONCLUSIONS: Infusion-site reactions were significantly reduced when fosaprepitant was diluted to 150 mg/250 ml and infused over 30 min. We recommend oncology pharmacists consider using the more dilute fosaprepitant preparation and 30 min infusion duration when administering via a peripheral intravenous line to improve patient tolerance.


Assuntos
Antieméticos/efeitos adversos , Morfolinas/efeitos adversos , Neoplasias/tratamento farmacológico , Antieméticos/uso terapêutico , Institutos de Câncer , Coleta de Dados , Feminino , Humanos , Incidência , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Morfolinas/administração & dosagem , Náusea/induzido quimicamente , Farmacêuticos/organização & administração , Estudos Retrospectivos , Vômito/induzido quimicamente
15.
Future Oncol ; 15(3): 297-303, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30301373

RESUMO

AIM: Fosaprepitant, an intravenous neurokinin-1 receptor antagonist for chemotherapy-induced nausea and vomiting, contains polysorbate 80, which is associated with infusion-site adverse events (ISAEs) and hypersensitivity systemic reactions (HSRs). This study investigated ISAEs/HSRs following fosaprepitant with anthracycline-containing chemotherapy. PATIENTS & METHODS: This retrospective chart review noted ISAEs/HSRs following the anthracycline doxorubicin+cyclophosphamide and a three-drug fosaprepitant regimen, via peripheral line. RESULTS: 35/127 patients (28%) developed ISAEs/HSRs with chemotherapy and antiemetic therapy: 32 developed 137 individual ISAEs, primarily erythema, pain and catheter-site swelling; 16 developed 50 individual HSRs, primarily edema/swelling, erythema or dermatitis (no anaphylaxis). CONCLUSION: Fosaprepitant is associated with a significant ISAE/HSR rate following anthracycline-containing chemotherapy via peripheral line. Polysorbate 80-free intravenous neurokinin-1 receptor antagonist may provide a safer chemotherapy-induced nausea and vomiting prophylaxis option.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/fisiopatologia , Morfolinas/efeitos adversos , Náusea/fisiopatologia , Antagonistas do Receptor de Neuroquinina-1/efeitos adversos , Vômito/fisiopatologia , Administração Intravenosa , Adulto , Idoso , Antraciclinas/efeitos adversos , Antraciclinas/uso terapêutico , Antieméticos/efeitos adversos , Antieméticos/uso terapêutico , Aprepitanto/efeitos adversos , Aprepitanto/uso terapêutico , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/classificação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Morfolinas/uso terapêutico , Náusea/induzido quimicamente , Antagonistas do Receptor de Neuroquinina-1/uso terapêutico , Polissorbatos/efeitos adversos , Polissorbatos/uso terapêutico , Vômito/induzido quimicamente
16.
Trials ; 19(1): 637, 2018 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-30454042

RESUMO

BACKGROUND: In patients with septic shock, the presence of an elevated heart rate (HR) after fluid resuscitation marks a subgroup of patients with a particularly poor prognosis. Several studies have shown that HR control in this population is safe and can potentially improve outcomes. However, all were conducted in a single-center setting. The aim of this multicenter study is to demonstrate that administration of the highly beta1-selective and ultrashort-acting beta blocker landiolol in patients with septic shock and persistent tachycardia (HR ≥ 95 beats per minute [bpm]) is effective in reducing and maintaining HR without increasing vasopressor requirements. METHODS: A phase IV, multicenter, prospective, randomized, open-label, controlled study is being conducted. The study will enroll a total of 200 patients with septic shock as defined by The Third International Consensus Definitions for Sepsis and Septic Shock criteria and tachycardia (HR ≥ 95 bpm) despite a hemodynamic optimization period of 24-36 h. Patients are randomized (1:1) to receive either standard treatment (according to the Surviving Sepsis Campaign Guidelines 2016) and continuous landiolol infusion to reach a target HR of 80-94 bpm or standard treatment alone. The primary endpoint is HR response (HR 80-94 bpm), the maintenance thereof, and the absence of increased vasopressor requirements during the first 24 h after initiating treatment. DISCUSSION: Despite recent studies, the role of beta blockers in the treatment of patients with septic shock remains unclear. This study will investigate whether HR control using landiolol is safe, feasible, and effective, and further enhance the understanding of beta blockade in patients with septic shock. TRIAL REGISTRATION: EU Clinical Trials Register; EudraCT, 2017-002138-22 . Registered on 8 August 2017.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Antiarrítmicos/uso terapêutico , Frequência Cardíaca/efeitos dos fármacos , Unidades de Terapia Intensiva , Morfolinas/uso terapêutico , Choque Séptico/tratamento farmacológico , Ureia/análogos & derivados , Antagonistas Adrenérgicos beta/efeitos adversos , Antiarrítmicos/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Ensaios Clínicos Fase IV como Assunto , Europa (Continente) , Humanos , Morfolinas/efeitos adversos , Estudos Multicêntricos como Assunto , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Choque Séptico/diagnóstico , Choque Séptico/fisiopatologia , Fatores de Tempo , Resultado do Tratamento , Ureia/efeitos adversos , Ureia/uso terapêutico , Vasoconstritores/uso terapêutico
17.
Clin Drug Investig ; 38(11): 1041-1051, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30194585

RESUMO

BACKGROUND AND OBJECTIVE: Imarikiren hydrochloride (TAK-272; SCO-272) is a novel direct renin inhibitor. The objective of this study was to determine the effects of renal impairment (RI) or hepatic impairment (HI) on the pharmacokinetics and safety of imarikiren. METHODS: This phase I, open-label, parallel-group comparative study evaluated the pharmacokinetics and safety of a single 40 mg oral dose of imarikiren in RI [mild, moderate, severe, or end-stage renal disease (ESRD), and on hemodialysis] or HI (mild or moderate) subjects compared with subjects with normal renal or hepatic function. RESULTS: Following administration of a single 40 mg oral imarikiren dose, the geometric mean imarikiren area under the plasma concentration-time curve from time zero to infinity (AUC∞) and maximum observed plasma concentration (Cmax) in subjects with mild, moderate, and severe RI (including non-hemodialysis and ESRD), and hemodialysis subjects compared with normal renal function subjects were approximately 0.5-, 1.2-, 2.7-, and 1.8-fold, respectively, for AUC∞; and approximately 0.6-, 0.8-, 2.1-, and 1.4-fold, respectively, for Cmax. The mean fraction of excretion of imarikiren in dialysate was ~ 3% during the 4 h dialysis period. The geometric mean imarikiren AUC∞ and Cmax in mild and moderate HI subjects compared with normal hepatic function subjects were approximately 1.0- and 1.4-fold, respectively, for AUC∞, and approximately 0.9- and 1.3-fold, respectively, for Cmax. No deaths or serious adverse events were observed; all adverse events were mild or moderate in intensity. CONCLUSIONS: RI and HI are associated with limited changes in imarikiren pharmacokinetics. Imarikiren was safe and well-tolerated, regardless of the severity of RI or HI. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02367872.


Assuntos
Benzimidazóis/administração & dosagem , Benzimidazóis/farmacocinética , Falência Renal Crônica/metabolismo , Hepatopatias/metabolismo , Morfolinas/administração & dosagem , Morfolinas/farmacocinética , Piperidinas/administração & dosagem , Piperidinas/farmacocinética , Adulto , Idoso , Área Sob a Curva , Benzimidazóis/efeitos adversos , Fármacos Cardiovasculares/administração & dosagem , Fármacos Cardiovasculares/efeitos adversos , Fármacos Cardiovasculares/farmacocinética , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/efeitos adversos , Inibidores Enzimáticos/farmacocinética , Feminino , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo , Falência Renal Crônica/tratamento farmacológico , Hepatopatias/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Morfolinas/efeitos adversos , Piperidinas/efeitos adversos , Diálise Renal/tendências
18.
BMC Cancer ; 18(1): 812, 2018 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-30103709

RESUMO

BACKGROUND: The irinotecan-induced phosphokinome changes in colorectal cancer (CRC) cells were used to guide the selection of targeted agents to be tested in combination with irinotecan. METHODS: Phosphokinome profiling with peptide arrays of tumour samples from nude mice xenografted with HT29 cells and treated or not with an effective dose of irinotecan was used to identify signalling pathways activated by irinotecan treatment. Then, drugs targeting these pathways were combined in vitro with irinotecan to test potential synergistic effect. The interactions between these drug combinations were assessed by a dose matrix approach. Confirmation of the most potential combination has been confirmed in vivo in xenografted mice. RESULTS: Irinotecan induced in vivo the activation of AKT and MEK1 phosphorylation. The dose matrix approach showed that BKM120 (PI3K inhibitor) and MEK162 (MEK inhibitor) are synergistic in vitro and in vivo with a cytostatic and cytotoxic effect, while combination of BKM120 and irinotecan or MEK162 and irinotecan are only additive or even antagonistic. However, the triple combination of SN38, BKM120 and MEK162 showed a better synergistic effect that BKM120 and MEK162, indicating that the cells need to inhibit both AKT and ERK pathways to become more sensitive to irinotecan-based chemotherapies. CONCLUSION: Analysis of chemotherapy-induced phosphokinome changes helps to elucidate the mechanisms of drug resistance and to guide the selection of targets for combination therapies with synergistic activity.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/genética , Sinergismo Farmacológico , Inibidores de Proteínas Quinases/administração & dosagem , Aminopiridinas/administração & dosagem , Aminopiridinas/efeitos adversos , Animais , Benzimidazóis/administração & dosagem , Benzimidazóis/efeitos adversos , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Camptotecina/análogos & derivados , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Células HT29 , Humanos , Irinotecano , MAP Quinase Quinase 1/antagonistas & inibidores , Camundongos , Terapia de Alvo Molecular , Morfolinas/administração & dosagem , Morfolinas/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Ann Oncol ; 29(9): 1918-1925, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-30016392

RESUMO

Background: We have previously shown that raised p-S6K levels correlate with resistance to chemotherapy in ovarian cancer. We hypothesised that inhibiting p-S6K signalling with the dual m-TORC1/2 inhibitor in patients receiving weekly paclitaxel could improve outcomes in such patients. Patients and methods: In dose escalation, weekly paclitaxel (80 mg/m2) was given 6/7 weeks in combination with two intermittent schedules of vistusertib (dosing starting on the day of paclitaxel): schedule A, vistusertib dosed bd for 3 consecutive days per week (3/7 days) and schedule B, vistusertib dosed bd for 2 consecutive days per week (2/7 days). After establishing a recommended phase II dose (RP2D), expansion cohorts in high-grade serous ovarian cancer (HGSOC) and squamous non-small-cell lung cancer (sqNSCLC) were explored in 25 and 40 patients, respectively. Results: The dose-escalation arms comprised 22 patients with advanced solid tumours. The dose-limiting toxicities were fatigue and mucositis in schedule A and rash in schedule B. On the basis of toxicity and pharmacokinetic (PK) and pharmacodynamic (PD) evaluations, the RP2D was established as 80 mg/m2 paclitaxel with 50 mg vistusertib bd 3/7 days for 6/7 weeks. In the HGSOC expansion, RECIST and GCIG CA125 response rates were 13/25 (52%) and 16/25 (64%), respectively, with median progression-free survival (mPFS) of 5.8 months (95% CI: 3.28-18.54). The RP2D was not well tolerated in the SqNSCLC expansion, but toxicities were manageable after the daily vistusertib dose was reduced to 25 mg bd for the following 23 patients. The RECIST response rate in this group was 8/23 (35%), and the mPFS was 5.8 months (95% CI: 2.76-21.25). Discussion: In this phase I trial, we report a highly active and well-tolerated combination of vistusertib, administered as an intermittent schedule with weekly paclitaxel, in patients with HGSOC and SqNSCLC. Clinical trial registration: ClinicialTrials.gov identifier: CNCT02193633.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Benzamidas/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/patologia , Morfolinas/administração & dosagem , Neoplasias Ovarianas/tratamento farmacológico , Inibidores de Proteínas Quinases/administração & dosagem , Pirimidinas/administração & dosagem , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Benzamidas/efeitos adversos , Benzamidas/farmacocinética , Carcinoma Pulmonar de Células não Pequenas/patologia , Esquema de Medicação , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Dose Máxima Tolerável , Alvo Mecanístico do Complexo 1 de Rapamicina/antagonistas & inibidores , Alvo Mecanístico do Complexo 2 de Rapamicina/antagonistas & inibidores , Pessoa de Meia-Idade , Morfolinas/efeitos adversos , Morfolinas/farmacocinética , Neoplasias Ovarianas/patologia , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Fosforilação/efeitos dos fármacos , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/farmacocinética , Pirimidinas/efeitos adversos , Pirimidinas/farmacocinética , Critérios de Avaliação de Resposta em Tumores Sólidos , Proteínas Quinases S6 Ribossômicas/metabolismo
20.
Future Oncol ; 14(27): 2849-2859, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29873529

RESUMO

AIM: Evaluate safety of HTX-019, a novel polysorbate 80- and synthetic surfactant-free intravenous formulation of neurokinin 1 receptor antagonist aprepitant for chemotherapy-induced nausea and vomiting. METHODS: Two open-label, randomized, two-way crossover studies evaluated treatment-emergent adverse events (TEAEs) in 200 healthy subjects. Subjects received HTX-019 130 mg (30-min infusion) and fosaprepitant 150 mg (20- or 30-min infusion), with ≥7-day washout between doses. RESULTS: Less than or equal to 30 min after start of infusion, TEAEs occurred in 5 (3%) HTX-019 and 30 (15%) fosaprepitant recipients. No HTX-019 recipients had infusion-site adverse events, versus 15 (8%) fosaprepitant recipients. Treatment-related dyspnea occurred in one HTX-019 and six fosaprepitant recipients. No severe/serious TEAEs occurred; all TEAEs resolved. CONCLUSION: HTX-019 may provide a safer aprepitant formulation than fosaprepitant for chemotherapy-induced nausea and vomiting prevention.


Assuntos
Antieméticos/efeitos adversos , Aprepitanto/efeitos adversos , Dispneia/epidemiologia , Morfolinas/efeitos adversos , Antagonistas do Receptor de Neuroquinina-1/efeitos adversos , Adulto , Antieméticos/administração & dosagem , Antineoplásicos/efeitos adversos , Aprepitanto/administração & dosagem , Estudos Cross-Over , Dispneia/induzido quimicamente , Feminino , Voluntários Saudáveis , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Morfolinas/administração & dosagem , Náusea/induzido quimicamente , Náusea/tratamento farmacológico , Neoplasias/tratamento farmacológico , Antagonistas do Receptor de Neuroquinina-1/administração & dosagem , Resultado do Tratamento , Vômito/induzido quimicamente , Vômito/tratamento farmacológico , Adulto Jovem
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