RESUMO
Pexidartinib is an orally administered small molecule tyrosine kinase inhibitor. Phase III ENLIVEN study results provided clinical evidence for US FDA approval for treatment of adult patients with symptomatic tenosynovial giant cell tumor associated with severe morbidity or functional limitations and not amenable to improvement with surgery. Recommended dosage is 400 mg orally twice daily on an empty stomach. Long-term follow-up in pooled analyses showed increased response rates compared with those observed in ENLIVEN. Patients on pexidartinib also experience meaningful improvements in range of motion. Side effects associated with pexidartinib are generally manageable; however, there is a risk of potentially life-threatening mixed or cholestatic hepatotoxicity and pexidartinib has a Risk Evaluation and Mitigation Strategy (REMS) program to ensure appropriate monitoring.
Assuntos
Aminopiridinas/uso terapêutico , Tumor de Células Gigantes de Bainha Tendinosa/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Pirróis/uso terapêutico , Aminopiridinas/química , Aminopiridinas/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ensaios Clínicos como Assunto , Diagnóstico por Imagem , Gerenciamento Clínico , Tumor de Células Gigantes de Bainha Tendinosa/diagnóstico , Tumor de Células Gigantes de Bainha Tendinosa/etiologia , Tumor de Células Gigantes de Bainha Tendinosa/mortalidade , Humanos , Terapia de Alvo Molecular , Estadiamento de Neoplasias , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Pirróis/química , Pirróis/farmacologia , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/antagonistas & inibidores , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/química , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/metabolismo , Relação Estrutura-Atividade , Resultado do TratamentoRESUMO
Osteochondral destruction and a high recurrence rate after surgery are major concerns that make difficult the treatment course of tenosynovial giant cell tumor. The aims of this study were to elucidate rates of postoperative local recurrence and osteochondral destruction, as correlated with various demographic factors. Eighty surgically treated patients with intra-articular tumors (knee: 49, ankle and foot: 12, hip: 10, others: 9) were included in this study. Factors including age, disease type (diffuse/localized), location, existence of osteochondral destruction were correlated with local recurrence or development/progression of osteochondral destruction. The 5-year local recurrence free survival rate was 71.4%. Diffuse type (n = 59, localized: n = 21) (P = 0.023) and knee location (P = 0.002) were independent risk factors for local recurrence. Diffuse type (P = 0.009) was a significant risk factor, and knee location (P = 0.001) was a negative factor for osteochondral destruction at the initial examination. Progression of osteochondral destruction was observed more often in cases with local recurrence (P = 0.040) and findings of osteochondral destruction at the initial examination (P = 0.029). Diffuse type is a factor that should be noted for both local recurrence and osteochondral destruction, while local recurrence occurs but osteochondral destruction is less observed in the knee.