Beyond ten cycles of cabazitaxel for castrate-resistant prostate cancer.

Background: There are limited data regarding cabazitaxel use beyond 10 cycles. Patients and Methods: Retrospective analysis of prospectively collected data of patients with metastatic castrate-resistant prostate cancer who received over 10 cycles of cabazitaxel after docetaxel failure. Results: Four patients received between 14 and 27 cycles. Reasons for stopping cabazitaxel were toxicity (2), progression (1) and logistics (1). Two of the three patients with measurable disease attained a partial remission (PR). Three patients continued to have a PSA response after 10 cycles; PSA nadir occurred between 17 and 23 cycles. Other than peripheral neuropathy (PN), all the cabazitaxel-related toxicities occurred after the initial cycles and did not increase cumulatively. Clinically significant neuropathy occurred after 15-17 cycles. The cabazitaxel-induced PN was partially reversible, with improvement from grade 3 to grade 2 after a 3-5-month long drug holiday. Conclusion: Cautiously continuing cabazitaxel until progression or intolerable toxicity may maximize efficacy.

A comparison of hemodynamic effects of levosimendan and dobutamine in patients undergoing mitral valve repair / replacement for severe mitral stenosis.

Aims and Objectives: We aimed to compare the hemodynamic effects of levosimendan and dobutamine in patients undergoing mitral valve surgery on cardiopulmonary bypass (CPB). Materials and Methods: Sixty patients were divided into 2 groups of 30 each. Group-L patients received levosimendan 0.1 μg/kg/min and Group-D patients received dobutamine 5 μg/kg/min while weaning off CPB. Additional inotrope and/or vasoconstrictor were started based on hemodynamic parameters. Hemodynamic data were collected at the end and at 30 minutes after CPB, thereafter at 6, 12, 24, and 36 hours post-CPB. Mean arterial pressure (MAP), central venous pressure (CVP), heart rate (HR), cardiac index (CI), systemic vascular resistance index (SVRI), and lactate levels were measured. Results: Group-L showed increased requirement of inotropes and vasoconstrictors. The SVRI, CVP, and MAP were reduced more in Group-L. The CI was low in Group-L in the initial period when compared to Group-D. Later Group-L patients showed a statistically significant increase in CI even after 12 hrs of discontinuation of levosimendan infusion. The HR was increased more in Group-D. Lactate levels, intensive care unit stay, and duration of ventilation were similar in both groups. Conclusions: Levosimendan 0.1 μg/kg/min compared to dobutamine 5 μg/kg/min showed more vasodilation and lesser inotropic activity in patients undergoing mitral valve surgery for mitral stenosis. Levosimendan compared to dobutamine showed a statistically significant increase in CI even after 12 hrs of discontinuation. The requirement of another inotrope or vasopressor was frequent in levosimendan group.

Levosimendana em pacientes com insuficiência cardíaca descompensada: eficácia em uma coorte brasileira. Resultados do estudo BELIEF / Levosimendan in decompensated heart failure patients: efficacy in a Brazilian cohort. Results of the BELIEF study

Fundamento: A levosimendana é um novo agente inodilatador que aumenta a contratilidade cardíaca pela sensibilização ao Ca(2+) e induz vasodilatação por meio da ativação dos canais KATP/BKCa. Objetivo: Estudar a eficácia e segurança da levosimendana em uma coorte brasileira portadora de insuficiência cardíaca descompensada e em pacientes resistentes a agonistas b-adrenérgicos. Métodos: O BELIEF (Brazilian Evaluation of Levosimendan Infusion Efficacy) foi um estudo aberto, prospectivo, multicêntrico e observacional realizado com 182 portadores de ICD de alto risco, todos tratados com levosimendana. O desfecho primário do estudo era alta hospitalar sem terapia inotrópica adicional (pacientes que responderam ao tratamento). Os desfechos secundários eram alterações nos parâmetros clínicos e hemodinâmicos e nos níveis de peptídeo natriurético cerebral (BNP). Resultados: A taxa de mortalidade foi de 14,8 por cento, e 139 dos 182 pacientes responderam ao tratamento. Entre os que não responderam, a taxa de mortalidade foi de 62,8 por cento. A pressão arterial sistólica foi um preditor de resposta ao tratamento. No grupo resistente aos agonistas b-adrenérgicos, 55,8 por cento responderam ao tratamento. Ao todo, 54 pacientes tiveram pelo menos um evento adverso, a maioria dos quais desapareceu espontaneamente ou após redução da dose da levosimendana. Houve uma melhora significativa na qualidade de vida entre 2 e 6 meses do acompanhamento (p < 0,0001). Conclusão: Nossos resultados indicam que a infusão de levosimendana é uma terapia alternativa de curto prazo para tratamento de pacientes com ICD. A gravidade da insuficiência cardíaca pode influenciar a resposta ao tratamento com levosimendana. São necessários estudos prospectivos com uma coorte brasileira que inclua também pacientes com doença de Chagas.

Background: Levosimendan is a new inodilatory agent that enhances cardiac contractility via Ca(2+) sensitization and induces vasodilation through the activation of KATP/BKCa. Objective: To study the efficacy and safety of levosimendan in a decompensated heart failure (DHF) Brazilian cohort, and in b-adrenergic agonist resistant patients. Methods: The Brazilian Evaluation of Levosimendan Infusion Efficacy (BELIEF) study was prospective, multicenter, observational and included 182 high-risk DHF patients, all of which received open-label levosimendan. Primary end point was hospital discharge without additional inotropic therapy (responder). Secondary end points were changes in hemodynamics, clinical parameters, and brain natriuretic peptide (BNP). Results: Mortality rate was 14.8 percent, and 139 of 182 patients were responders. In non responders it was 62.8 percent. Systolic blood pressure was a predictor of response. In b-adrenergic agonist resistant group, 55.8 percent were responders. Overall, 54 patients experienced at least one adverse event; most of them resolved either spontaneously or after levosimendan dose reduction. A significant improvement in quality of life was verified at 2-6 months of follow-up (p<0.0001). Conclusion: Our results suggest levosimendan infusion as an alternative therapy in the short term management of DHF patients. HF severity can influence the response to levosimendan treatment. Prospective studies are warranted in a Brazilian cohort including Chagas heart disease.

Uso de levosimendana em diversos quadros de insuficiência cardíaca aguda: [revisão] / Levosimendan use in several scenarios of acute heart failure: [review]

Nos países em que é comercializada, a administração precoce de levosimendana deve ser considerada em pacientes que permanecem sintomáticos e com dispnéia em repouso apesar da terapia inicial, principalmente aqueles com história de insuficiência cardíaca crônica ou em tratamento prolongado com betabloqueadores. Pacientes hipotensos ou com isquemia ativa não são os melhores candidatos para receber infusão de levosimendana e precisam, primeiro, ter esses problemas tratados.

In countries where it is available, early levosimendan infusion can be considered for patients who remain symptomatic with dyspnea at rest despite initial therapy, particularly those with a history of chronic heart failure or chronically treated with beta-blockers. Hypotensive patients or patients with active ischemia are not the best candidates for levosimendan administration and should have these problems addressed first.

Uso del levosimendan previo a la cirugía cardíaca, en pacientes con mala función ventricular / Usefulness of levosimendan in patients with ventricular dysfunction before surgery

El propósito de este trabajo fue observar los resultados hemodinámicos inmediatos (primeras 24 hs) en pacientes con mala función ventricular (< 40%), considerados de alto riesgo quirúrgico, en los cuales 24 a 48 hs antes de la cirugía recibían una infusión por 24 hs con levosimendan. Se incluyeron 4 pacientes de sexo masculino con edad promedio de 55.50 (+ 7.93 años) con una fracción de eyección del ventrículo izquierdo de 31 (+ 5.47%), 2 de ellos sometidos a cambio valvular, otro a revascularización miocárdica y el cuarto se sometió a procedimiento combinado (revascularización + cambio valvular). El comportamiento de los parámetros hemodinámicos estuvo estable, sin necesidad de altas dosis de los inotrópicos y vasopresores clásicos en el postoperatorio. Conclusión: El levosimendan podría ser un inotrópico de gran aplicación en este grupo de pacientes debido a su novedoso mecanismo de acción y a sus sostenidos efectos hemodinámicos luego de terminada su infusión.

The purpose of this work was to observe the hemodynamic stability on the first 24 hours in 4 patients with ventricular dysfunction (Ejected Fraction < 40 %), considered of high surgical risk, in which 24 at 48 hr before the surgery received an infusion of Levosimendan for 24 hours. This 4 patients was male, with age 55.5 ± 7.9 years old, a left ventricle ejection of fraction (LVEF) of 31 ± 5.47%; Two of them was underwent to valve replacement, another one to coronary artery bypass graft and the last one patient underwent combined procedure (coronary artery bypass graft surgery and valve replacement). The behavior of the hemodynamic parameters was stable, without necessity of uses high dose of the inotropics and classic vasopresores in the postoperative. Conclusion: the Levosimendan could be an inotropic of great application in this group of patient due to its novel action mechanism and to its sustained hemodynamic effects after having finished its infusion.