RESUMO
Aim: Evaluate health-related quality of life (HRQoL) and health utility impact of single-agent selinexor in heavily pretreated patients with relapsed/refractory diffuse large B-cell lymphoma. Patients & methods: Functional Assessment of Cancer Therapy (FACT) - Lymphoma and EuroQoL five-dimensions five-levels data collected in the single-arm Phase IIb trial SADAL (NCT02227251) were analyzed with mixed-effects models. Results: Treatment responders maintained higher FACT - Lymphoma (p ≤ 0.05), FACT - General (p < 0.05) and EuroQoL five-dimensions five-levels index scores (p < 0.001) beginning in cycle 3. The estimated difference in health state utilities for treatment response and progressive disease was both statistically significant and clinically meaningful (mean difference: 0.07; p = 0.001). Conclusion: In patients with relapsed/refractory diffuse large B-cell lymphoma, objective response to selinexor was associated with HRQoL maintenance, reduction in disease-related HRQoL decrements and higher health utilities.
Lay abstract This work examined quality of life (QoL) among patients with relapsed/refractory diffuse large B-cell lymphoma with two to five prior therapies who received single-agent selinexor in the SADAL clinical trial. Analysis of patient-reported Functional Assessment of Cancer Therapy Lymphoma and EuroQoL five-dimensions five-levels data showed that patients who had objective clinical response to selinexor maintained their QoL over the course of treatment. Grade ≥3 adverse events and serious adverse events were not associated with clinically meaningful negative QoL impacts. Clinical trial registration: NCT02227251 (ClinicalTrials.gov).
Assuntos
Hidrazinas/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Triazóis/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , RecidivaRESUMO
Cigarette smoking is one of the risk factors for coronary artery disease. Although conditioning decreases infarct size in hearts from healthy animals, comorbidities may render it ineffective. We investigated the effects of cigarette smoke (CS) exposure on intracellular myocardial signaling, infarct size after ischemia-reperfusion, and the potential interference with ischemic conditioning. Exposure of mice to CS increased blood pressure, caused cardiac hypertrophy, and upregulated the nitric oxide synthatse (NOS)/soluble guanylate cyclase (sGC)/cGMP pathway. To test the effect of CS exposure on the endogenous cardioprotective mechanisms, mice were subjected to regional myocardial ischemia and reperfusion with no further intervention or application of preconditioning (PreC) or postconditioning (PostC). Exposure to CS did not increase the infarction compared with the room air (RA)-exposed group. PreC was beneficial for both CS and RA vs. nonconditioned animals. PostC was effective only in RA animals, while the infarct size-limiting effect was not preserved in the CS group. Differences in oxidative stress markers, Akt, and endothelial NOS phosphorylation and cGMP levels were observed between RA and CS groups subjected to PostC. In conclusion, exposure to CS does not per se increase infarct size. The beneficial effect of ischemic PreC is preserved in mice exposed to CS, as it does not affect the cardioprotective signaling; in contrast, PostC fails to protect CS-exposed mice due to impaired activation of the Akt/eNOS/cGMP axis that occurs in parallel to enhanced oxidative stress.