JCO:VSLI用于晚期ALL患效果积极
2012-12-12 Jco Jco
美国Talon Therapeutics公司Susan O’Brien等人在2012年11月19日在线出版的《临床肿瘤学杂志》(Journal of Clinical Oncology)上,发表了一篇关于硫酸长春新碱(VCR)脂质体注射液治疗晚期急性淋巴细胞白血病(ALL)患者的临床试验结果。急性淋巴细胞白血病成年患者病情复发与较高的再诱导治疗死亡率、化疗耐药性以及可导致死亡的快速进展间存在联系。
美国Talon Therapeutics公司Susan O’Brien等人在2012年11月19日在线出版的《临床肿瘤学杂志》(Journal of Clinical Oncology)上,发表了一篇关于硫酸长春新碱(VCR)脂质体注射液治疗晚期急性淋巴细胞白血病(ALL)患者的临床试验结果。急性淋巴细胞白血病成年患者病情复发与较高的再诱导治疗死亡率、化疗耐药性以及可导致死亡的快速进展间存在联系。硫酸长春新碱脂质体注射液(VSLI)、鞘磷脂与胆固醇纳米长春新碱都有助于增强长春新碱剂量强度和稠度,并可提高药物在靶点组织中的释放。因此研究人员针对多次复发的费城染色体(Ph)呈阴性、复发后对再诱导治疗产生耐受的成年急性淋巴细胞白血病患者,以及/或在造血干细胞移植后出现复发的患者,评价了高剂量VSLI单剂在此类患者中的应用。
该项研究为一项多中心关键性临床II期试验,共有65例Ph阴性的ALL成年患者参与,他们均曾出现过再次或更多次的复发情况,或者在接受两次或更多次白血病治疗后病情仍出现进展。在无剂量限制的情况下,按照2.25 mg/m2剂量,每周静脉注射一次VSLI ,直至患者病情缓解、出现进展、发生毒性反应或进行造血干细胞移植。该项研究的主要终点为,取得完全缓解(CR)或不完全血象恢复下的完全缓解(CRi)。
在该项研究中,参试患者CR/CRi为20%,总缓解率为35%。研究人员认为, VSLI单剂可作为一种有效的三线、四线以及五线治疗方法,可用于对其他采用单一药物与多药物进行再次诱导治疗产生耐药性的患者。他们发现,患者平均CR/CRi维持时间为23周(浮动范围。5周至66周);有12例患者在VSLI治疗后进行造血干细胞移植,5例患者长期存活。此外,VSLI的总体耐受性良好,并且其30日死亡率较低(12%)。
因此,研究人员认为,针对晚期急性淋巴细胞白血病患者,高剂量VSLI单剂治疗在临床预后方面具有深远意义,包括可形成持久性缓解以及衔接造血干细胞移植。尽管与常规VCR相比,VSLI药物释放量较大,常规VCR单一与累计剂量无法达到同等药物释放量,但在毒理特性方面,VSLI仍具有可预测性、可控性。
High-Dose Vincristine Sulfate Liposome Injection for Advanced, Relapsed, and Refractory Adult Philadelphia Chromosome–Negative Acute Lymphoblastic Leukemia
Purpose
Relapsed adult acute lymphoblastic leukemia (ALL) is associated with high reinduction mortality, chemotherapy resistance, and rapid progression leading to death. Vincristine sulfate liposome injection (VSLI), sphingomyelin and cholesterol nanoparticle vincristine (VCR), facilitates VCR dose-intensification and densification plus enhances target tissue delivery. We evaluated high-dose VSLI monotherapy in adults with Philadelphia chromosome (Ph) –negative ALL that was multiply relapsed, relapsed and refractory to reinduction, and/or relapsed after hematopoietic cell transplantation (HCT).
Patients and Methods
Sixty-five adults with Ph-negative ALL in second or greater relapse or whose disease had progressed following two or more leukemia therapies were treated in this pivotal phase II, multinational trial. Intravenous VSLI 2.25 mg/m2, without dose capping, was administered once per week until response, progression, toxicity, or pursuit of HCT. The primary end point was achievement of complete response (CR) or CR with incomplete hematologic recovery (CRi).
Results
The CR/CRi rate was 20% and overall response rate was 35%. VSLI monotherapy was effective as third-, fourth-, and fifth-line therapy and in patients refractory to other single- and multiagent reinduction therapies. Median CR/CRi duration was 23 weeks (range, 5 to 66 weeks); 12 patients bridged to a post-VSLI HCT, and five patients were long-term survivors. VSLI was generally well tolerated and associated with a low 30-day mortality rate (12%).
Conclusion
High-dose VSLI monotherapy resulted in meaningful clinical outcomes including durable responses and bridging to HCT in advanced ALL settings. The toxicity profile of VSLI was predictable, manageable, and comparable to standard VCR despite the delivery of large, normally unachievable, individual and cumulative doses of VCR.
与硫酸长春新碱相关的拓展阅读:
版权声明:
本网站所有注明“来源:梅斯医学”或“来源:MedSci原创”的文字、图片和音视频资料,版权均属于梅斯医学所有。非经授权,任何媒体、网站或个人不得转载,授权转载时须注明“来源:梅斯医学”。其它来源的文章系转载文章,本网所有转载文章系出于传递更多信息之目的,转载内容不代表本站立场。不希望被转载的媒体或个人可与我们联系,我们将立即进行删除处理。
在此留言
#JCO#
0
#ALL#
37