Vincristine sulfate liposomal injection for acute lymphoblastic leukemia

Abstract

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.

Keywords: acute lymphoblastic leukemia; chemotherapy; liposomes; sphingosomal vincristine; vincristine sulfate liposomal injection.

Figure 1

Phospholipids contain a glycerophosphate backbone covalently bonded to a polar head group and two fatty acyl tails. The bipolar nature of the phospholipid permits the formation of bilayer membranes in which proteins, cofactors, or chemical compounds such as vincristine can be encapsulated.