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1.
Clin Cancer Res ; 29(8): 1460-1467, 2023 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-36730323

RESUMO

PURPOSE: In the dose-expansion part of this open-label, phase I study, we explored the efficacy and safety of E7389-LF (liposomal formulation of eribulin) in Japanese patients with advanced gastric cancer. PATIENTS AND METHODS: Patients with advanced gastric cancer who had been previously treated with ≥2 lines of chemotherapy received E7389-LF 2.0 mg/m2 every 3 weeks (the previously determined maximum tolerated dose, the primary objective of Study 114). Secondary objectives included objective response rate (ORR), progression-free survival (PFS), and safety; exploratory objectives included disease control rate (DCR) and clinical benefit rate (CBR), as well as pharmacodynamic measurements of serum biomarkers. RESULTS: As of June 24, 2021, 34 patients were enrolled and treated (10 from the original dose-expansion cohort, expanded to include 24 additional patients). Six patients had partial responses, for an ORR of 17.6% [95% confidence interval (CI), 6.8-34.5], and the median PFS was 3.7 months (95% CI, 2.7-4.8). The DCR was 79.4% (95% CI, 62.1-91.3), and the CBR was 32.4% (95% CI, 17.4-50.5). Overall, 32 patients (94.1%) experienced treatment-related adverse events, and 26 patients (76.5%) experienced grade ≥3 events, most commonly neutropenia (41.2%) and leukopenia (29.4%). Of the 8 endothelial cell/vasculature markers tested in this study, 7 were significantly increased among patients treated with E7389-LF; these changes were generally consistent regardless of best overall response. CONCLUSIONS: E7389-LF 2.0 mg/m2 every 3 weeks was tolerable and showed preliminary activity for the treatment of patients with gastric cancer.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Furanos/efeitos adversos , Cetonas/efeitos adversos , Intervalo Livre de Progressão
2.
Endocrine ; 56(1): 121-128, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28155175

RESUMO

PURPOSE: In the study of (E7080) lenvatinib in differentiated cancer of the thyroid, most patients experienced an adverse event. In this report, we examine common lenvatinib-emergent adverse events in this phase three, randomized, double-blind study. METHODS: Adverse events were graded per Common Terminology Criteria for Adverse Events v4.0. 392 patients were enrolled (lenvatinib: 261, placebo: 131) and received lenvatinib 24 mg/day or placebo. The main outcome measures were: associations with progression-free survival and overall survival in exploratory univariate and multivariate analyses along with additional variables. RESULTS: The most common any-grade adverse events (any grade; grade 3) in lenvatinib-treated patients included proteinuria (32%; 10%), diarrhea (67%; 9%), fatigue/asthenia/malaise (67%; 10%), rash (23%; 0.4%), and palmar-plantar erythrodysesthesia syndrome (33%; 3%). There were no grade 4 events for these adverse events. They generally occurred early (median time to first onset [weeks]: proteinuria [6.1], diarrhea [12.1], fatigue/asthenia/malaise [3.0], rash [7.3], and palmar-plantar erythrodysesthesia syndrome [5.9]), and were resolved primarily with dose modifications (median time to resolution [weeks]: proteinuria [8.8], diarrhea [18.1], fatigue/asthenia/malaise [16.3], rash [5.9], and palmar-plantar erythrodysesthesia syndrome [20.0]). Discontinuation due to these adverse events occurred in 2 (1%) patients with proteinuria and 4 (2%) with fatigue. Progression-free survival was not associated with any of the adverse events. Eastern Cooperative Oncology Group performance status (P = 0.001), follicular histology (P = 0.002), and diarrhea (P = 0.023) were associated with overall survival in multivariate analyses (median overall survival for patients with diarrhea: not reached; without: 17.1 months). CONCLUSIONS: In the study of (E7080) lenvatinib in differentiated cancer of the thyroid, the most common adverse events typically occurred early and were primarily managed with dose modifications. Overall survival was significantly associated with diarrhea.


Assuntos
Antineoplásicos/efeitos adversos , Diarreia/epidemiologia , Exantema/epidemiologia , Fadiga/epidemiologia , Compostos de Fenilureia/efeitos adversos , Proteinúria/epidemiologia , Quinolinas/efeitos adversos , Neoplasias da Glândula Tireoide/tratamento farmacológico , Antineoplásicos/uso terapêutico , Diarreia/induzido quimicamente , Intervalo Livre de Doença , Método Duplo-Cego , Exantema/induzido quimicamente , Fadiga/induzido quimicamente , Feminino , Humanos , Incidência , Masculino , Compostos de Fenilureia/uso terapêutico , Proteinúria/induzido quimicamente , Quinolinas/uso terapêutico , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/patologia , Resultado do Tratamento
3.
Leuk Lymphoma ; 56(2): 390-4, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24844364

RESUMO

Myelosuppression in myelodysplastic syndromes (MDS) is associated with the hypomethylating agent decitabine. A retrospective pooled analysis of two decitabine clinical trials in patients with MDS conducted Cox regression analyses of red blood cell or platelet dependence, myelosuppression, dose modification, cycle delay or dose reduction, and survival effects. In 182 patients, baseline platelet dependence was a predictor for dose modification, reduction or delay, and death (modification: p=0.006, hazard ratio [HR]=2.04; reduction/delay: p=0.011, HR=2.00; death: p=0.003, HR=1.94). Patients with dose modifications had significantly higher overall response rates versus those with none (22% vs. 10%; p=0.015). Patients with no dose modifications had faster progression to acute myeloid leukemia (AML) versus patients with dose modifications (p=0.004). Without dose modifications, patients tended to drop out due to disease progression or other reasons. Decitabine dose modifications on treatment may indicate response to treatment.


Assuntos
Azacitidina/análogos & derivados , Leucemia Mieloide/tratamento farmacológico , Síndromes Mielodisplásicas/tratamento farmacológico , Doença Aguda , Idoso , Antimetabólitos Antineoplásicos/uso terapêutico , Azacitidina/uso terapêutico , Decitabina , Progressão da Doença , Relação Dose-Resposta a Droga , Feminino , Humanos , Estimativa de Kaplan-Meier , Leucemia Mieloide/patologia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/patologia , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Modelos de Riscos Proporcionais , Estudos Retrospectivos
4.
J Neurotrauma ; 31(3): 239-55, 2014 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-23859435

RESUMO

A prospective, multicenter phase I trial was undertaken by the North American Clinical Trials Network (NACTN) to investigate the pharmacokinetics and safety of, as well as obtain pilot data on, the effects of riluzole on neurological outcome in acute spinal cord injury (SCI). Thirty-six patients, with ASIA impairment grades A-C (28 cervical and 8 thoracic) were enrolled at 6 NACTN sites between April 2010 and June 2011. Patients received 50 mg of riluzole PO/NG twice-daily, within 12 h of SCI, for 14 days. Peak and trough plasma concentrations were quantified on days 3 and 14. Peak plasma concentration (Cmax) and systemic exposure to riluzole varied significantly between patients. On the same dose basis, Cmax did not reach levels comparable to those in patients with amyotrophic lateral sclerosis. Riluzole plasma levels were significantly higher on day 3 than on day 14, resulting from a lower clearance and a smaller volume of distribution on day 3. Rates of medical complications, adverse events, and progression of neurological status were evaluated by comparison with matched patients in the NACTN SCI Registry. Medical complications in riluzole-treated patients occurred with incidences similar to those in patients in the comparison group. Mild-to-moderate increase in liver enzyme and bilirubin levels were found in 14-70% of patients for different enzymes. Three patients had borderline severe elevations of enzymes. No patient had elevated bilirubin on day 14 of administration of riluzole. There were no serious adverse events related to riluzole and no deaths. The mean motor score of 24 cervical injury riluzole-treated patients gained 31.2 points from admission to 90 days, compared to 15.7 points for 26 registry patients, a 15.5-point difference (p=0.021). Patients with cervical injuries treated with riluzole had more-robust conversions of impairment grades to higher grades than the comparison group.


Assuntos
Fármacos Neuroprotetores/uso terapêutico , Riluzol/uso terapêutico , Traumatismos da Medula Espinal/tratamento farmacológico , Adolescente , Adulto , Idoso , Vértebras Cervicais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fármacos Neuroprotetores/efeitos adversos , Fármacos Neuroprotetores/farmacocinética , Recuperação de Função Fisiológica/efeitos dos fármacos , Riluzol/efeitos adversos , Riluzol/farmacocinética , Vértebras Torácicas , Adulto Jovem
5.
Clin Lymphoma Myeloma Leuk ; 13(5): 592-6, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23790798

RESUMO

BACKGROUND: After the World Health Organization (WHO) changed the definition of acute myeloid leukemia (AML) to ≥ 20% blasts, the International Working Group (IWG) response criteria for myelodysplasia were updated. This retrospective analysis evaluated response to decitabine using updated IWG criteria in patients pooled from 2 decitabine trials. PATIENTS AND METHODS: Outcomes for patients with myelodysplastic syndrome (MDS) with baseline marrow blasts ≥ 20% and < 30% (RAEB-t group) and < 20% (MDS group) were compared. RESULTS: Patients with RAEB-t (n = 26) had a significantly shorter time from diagnosis to study treatment (7.3 vs. 18.3 months), a higher International Prognostic Scoring System (IPSS) risk (77% vs. 16% high-risk patients), and lower median baseline platelet count (62.3 vs. 112.7 × 10(3)/µL) vs. patients with MDS (n = 157), yet no significant difference in overall response rate (ORR) (15.4% vs. 28.0%). Patients with MDS had better duration of response (9.9 vs. 5 months; P = .024) and overall survival (OS) (16.6 vs. 9.0 months; P = .021) compared with patients with RAEB-t. CONCLUSION: Decitabine is active in and may benefit patients with > 20% blasts (RAEB-t).


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Azacitidina/análogos & derivados , Medula Óssea/patologia , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/patologia , Idoso , Idoso de 80 Anos ou mais , Azacitidina/uso terapêutico , Decitabina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
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