结外自然杀伤/T细胞淋巴瘤(ENKTL)患者,鼻型受益于PEG-天冬酰胺酶,吉西他滨,和甲氨蝶呤.因此,我们在初治ENKTL患者中使用这些药物的组合作为GAD-M方案进行了一项前瞻性II期试验,同时,探索了组合机制。GAD-M方案在I/II期放疗和III/IV期放疗中夹6个周期。6个周期后,36例患者的总有效率为91.6%,完全缓解率上升至83.3%。3年无进展生存率(PFS)和总生存率(OS)分别为74.8%和77.8%,分别。5年PFS和OS分别为68.3%和77.8%。没有患者患有中枢神经系统(CNS)复发。在这项研究中,大多数患者经历了可恢复的肝功能障碍和贫血。在第一个周期内12至24小时的血浆MTX浓度比可能是ENKTL结果的早期预测指标(PFS,P=0.005;OS,P=0.002)。此外,我们发现高剂量MTX(HD-MTX)和吉西他滨在体外对ENKTL细胞有协同作用。机械上,我们证明,该组合可导致ENKTL细胞明显凋亡,并释放活性氧香料(ROS),由内质网应激介导。总之,GAD-M方案可能是新诊断ENKTL的新选择,尤其是I/II期患者。此外,我们的结果表明HD-MTX与吉西他滨在ENKTL中的协同作用。
背景:该试验已在www注册。clinicaltrials.gov作为#NCT01991158。
Patients with extranodal natural killer/T-cell lymphoma (ENKTL), nasal type are benefit from peg-asparaginase, gemcitabine, and methotrexate. Therefore, we conducted a prospective phase II trial using a combination of these drugs as GAD-M regimen in naïve ENKTL patients, simultaneously, explored the combinational mechanism. The GAD-M regimen was administered for 6 cycles sandwiched by radiotherapy for stage I/II and 6 cycles for stage III/IV patients. After 6 cycles, the overall response rate of 36 patients was 91.6%, and the complete remission rate increased to 83.3%. The 3-year progression-free survival (PFS) and overall survival (OS) rates were 74.8% and 77.8%, respectively. The 5-year PFS and OS were 68.3% and 77.8%. No patient suffered from the central nervous system (CNS) relapse. Most patients experienced recoverable liver dysfunction and anemia in this study. The plasma MTX concentration ratio at 12 to 24 hr during the first cycle could be an early predictor of outcomes in ENKTL (PFS, P=0.005; OS, P=0.002). Additionally, we found that high dose MTX (HD-MTX) and gemcitabine had the synergistic effect of ENKTL cell in vitro. Mechanistically, we demonstrated that the combination could lead to obviously apoptosis in ENKTL cell with extremely release of reactive oxygen spices (ROS), which mediated by endoplasmic reticulum stress. In conclusion, the GAD-M regimen could be a new choice to newly diagnosed ENKTL, especially for stage I/II patients. Furthermore, our results showed the synergy effect of HD-MTX with gemcitabine in ENKTL.
BACKGROUND: This trial was registered at www.clinicaltrials.gov as #NCT01991158.