Royal Children's Hospital, Children's Health Queensland Hospital and Health Service, Brisbane, Queensland, Australia.
Int J Nanomedicine. 2013;8:4361-9. doi: 10.2147/IJN.S54657. Epub 2013 Nov 6.
Vincristine (VCR) is one of the most extensively used cytotoxic compounds in hemato-oncology. VCR is particularly important for the treatment of acute lymphoblastic leukemia (ALL), a disease that accounts for approximately one-third of all childhood cancer diagnoses. VCR's full therapeutic potential has been limited by dose-limiting neurotoxicity, classically resulting in autonomic and peripheral sensory-motor neuropathy. In the last decade, however, the discovery that liposomal encapsulation of chemotherapeutics can modulate the pharmacokinetic characteristics of a compound has stimulated much interest in liposomal VCR (vincristine sulfate liposomal injection [VSLI]) formulations for the treatment of ALL and other hematological malignancies. Promising data from recent clinical trials investigating VSLI in adults with ALL resulted in US Food and Drug Administration approval for use in patients with Philadelphia chromosome (t[9;22]/BCR-ABL1) (Ph)-negative (Ph-) disease. Additional clinical trials of VSLI in adults and children with both Ph-positive (Ph+) and Ph- ALL are ongoing. Here we review the preclinical and clinical experience to date with VSLI for ALL.
长春新碱(VCR)是血液肿瘤学中最广泛使用的细胞毒性化合物之一。VCR 对于治疗急性淋巴细胞白血病(ALL)尤为重要,ALL 约占所有儿童癌症诊断的三分之一。VCR 的全部治疗潜力受到剂量限制的神经毒性的限制,其典型表现为自主和周围感觉运动神经病。然而,在过去十年中,发现化疗药物的脂质体包封可以调节化合物的药代动力学特征,这激发了人们对脂质体长春新碱(硫酸长春新碱脂质体注射液[VSLI])制剂治疗 ALL 和其他血液系统恶性肿瘤的极大兴趣。最近的临床试验中,VSLI 在成人 ALL 中的令人鼓舞的数据导致美国食品和药物管理局批准其用于费城染色体(t[9;22]/BCR-ABL1)(Ph)阴性(Ph-)疾病患者。VSLI 在 Ph+和 Ph-ALL 成人和儿童中的额外临床试验正在进行中。在这里,我们回顾了迄今为止 VSLI 治疗 ALL 的临床前和临床经验。