RESUMO
The United States Food and Drug Administration has permitted number of therapeutic agents for cancer treatment. Most of them are expensive and have some degree of systemic toxicity which makes overbearing in clinical settings. Although advanced research continuously applied in cancer therapeutics, but drug resistance, metastasis, and recurrence remain unanswerable. These accounts to an urgent clinical need to discover natural compounds with precisely safe and highly efficient for the cancer prevention and cancer therapy. Gambogic acid (GA) is the principle bioactive and caged xanthone component, a brownish gamboge resin secreted from the of Garcinia hanburyi tree. This molecule showed a spectrum of biological and clinical benefits against various cancers. In this review, we document distinct biological characteristics of GA as a novel anti-cancer agent. This review also delineates specific molecular mechanism(s) of GA that are involved in anti-cancer, anti-metastasis, anti-angiogenesis, and chemo-/radiation sensitizer activities. Furthermore, recent evidence, development, and implementation of various nanoformulations of gambogic acid (nanomedicine) have been described.
Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Nanomedicina/métodos , Neoplasias/terapia , Radiossensibilizantes/administração & dosagem , Xantonas/administração & dosagem , Animais , Antineoplásicos Fitogênicos/economia , Quimiorradioterapia/economia , Quimiorradioterapia/métodos , Ensaios Clínicos Fase II como Assunto , Relação Dose-Resposta a Droga , Portadores de Fármacos/química , Custos de Medicamentos , Garcinia/química , Humanos , Nanomedicina/economia , Nanopartículas/química , Neoplasias/economia , Radiossensibilizantes/economia , Resinas Vegetais/química , Resultado do Tratamento , Xantonas/economia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
INTRODUCTION: The irreversible ErbB family blocker afatinib and the reversible EGFR tyrosine kinase inhibitor gefitinib were compared in the multicenter, international, randomized, head-to-head phase 2b LUX-Lung 7 trial for first-line treatment of advanced EGFR mutation-positive NSCLCs. Afatinib and gefitinib costs and patients' outcomes in France were assessed. METHODS: A partitioned survival model was designed to assess the cost-effectiveness of afatinib versus gefitinib for EGFR mutation-positive NSCLCs. Outcomes and safety were taken primarily from the LUX-Lung 7 trial. Resource use and utilities were derived from that trial, an expert-panel questionnaire, and published literature, limiting expenditures to direct costs. Incremental cost-effectiveness ratios (ICERs) were calculated over a 10-year time horizon for the entire population, and EGFR exon 19 deletion or exon 21 L858R mutation (L858R) subgroups. Deterministic and probabilistic sensitivity analyses were conducted. RESULTS: For all EGFR mutation-positive NSCLCs, the afatinib-versus-gefitinib ICER of was 45,211 per quality-adjusted life-year (QALY) (0.170 QALY gain for an incremental cost of 7697). ICERs for EGFR exon 19 deletion and L858R populations were 38,970 and 52,518, respectively. Afatinib had 100% probability to be cost-effective at a willingness-to-pay threshold of 70,000/QALY for patients with common EGFR mutations. CONCLUSION: First-line afatinib appears cost-effective compared with gefitinib for patients with EGFR mutation-positive NSCLCs.