RESUMO
The prevention and treatment of chemotherapy-induced nausea and vomiting (CINV) continues to pose a challenge for clinicians. The development of 5-hydroxytryptamine (serotonin) antagonists and neurokinin-1 receptor antagonists (NK1 -RAs) have demonstrated significant improvements in acute and delayed CINV for highly and moderately emetogenic chemotherapy. Delayed and breakthrough CINV, however, continue to be difficult to manage despite available treatment agents. Randomized clinical trial data suggest that olanzapine, a second-generation thienobenzodiazepine, traditionally used in the treatment of manifestations of psychotic disorders, is an effective agent in these clinical settings. The short-term use of olanzapine has a favorable adverse event profile and was not associated with grade 3 or 4 toxicity in a phase III study. Olanzapine is recommended as an option within first-line prophylaxis for CINV in the National Comprehensive Cancer Network (NCCN) guidelines and is an option for treatment of refractory CINV in the Multinational Association of Supportive Care in Cancer/European Society for Medical Oncology and NCCN guidelines.
Assuntos
Antieméticos/uso terapêutico , Antineoplásicos/efeitos adversos , Benzodiazepinas/uso terapêutico , Medicina Baseada em Evidências , Náusea/prevenção & controle , Antagonistas da Serotonina/uso terapêutico , Vômito/prevenção & controle , Antieméticos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Benzodiazepinas/efeitos adversos , Institutos de Câncer , Humanos , Agências Internacionais , Náusea/induzido quimicamente , Náusea/tratamento farmacológico , Olanzapina , Guias de Prática Clínica como Assunto , Antagonistas da Serotonina/efeitos adversos , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Sociedades Hospitalares , Sociedades Médicas , Vômito/induzido quimicamente , Vômito/tratamento farmacológicoRESUMO
FMS-like tyrosine kinase-3 (FLT3) is a member of the class III membrane receptor tyrosine kinase family and is important in survival, proliferation and differentiation of hematopoietic cells. FLT3 is mutated in approximately 30% of acute myelogenous leukemia patients. These mutations involve internal tandem duplications in the juxtamembrane domain of the receptor and tyrosine kinase point mutations in the activation loop. Over the past decade, due to the incidence and poor prognosis associated with FLT3, numerous agents have been developed to directly inhibit the activity of wild type and mutated FLT3. In this review, we focus on the preclinical data demonstrating in vitro activity, inhibition of downstream signaling pathways and potential synergy with traditional chemotherapeutic agents. Also, early clinical trial data specifically focusing on drug toxicity, clinical efficacy and future directions of FLT3-directed anticancer therapy are discussed.