Pharmacokinetics and pharmacodynamics of vincristine sulfate liposome injection (VSLI) in adults with acute lymphoblastic leukemia

Abstract

Vincristine sulfate liposome injection (VSLI,) is a sphingomyelin and cholesterol nanoparticle formulation of vincristine sulfate (VCR) that was designed to overcome the dosing and pharmacokinetic limitations of standard VCR. In contrast to the rapid CL and wide tissue distribution of non-liposomal VCR, VSLI circulates in plasma for a prolonged period of time, with a slow CL of 345 mL/h and relatively small Vd of 3,570 mL. This facilitates enhanced and prolonged tumor-tissue delivery of VCR. The maximum tolerated dose of VSLI, 2.25 mg/m(2) once per week without a dose cap, enables individual and cumulative VCR exposure unachievable with non-liposomal VCR at its labeled dose of 1.4 mg/m(2) . VSLI is associated with a dose-dependent peripheral neurotoxicity albeit at doses that are two to three times that of standard VCR. VCR dose intensification with VSLI correlated with an increased probability of overall response and a strong trend towards increased complete response in adults with relapsed and/or refractory acute lymphoblastic leukemia. Overall, VSLI improves the therapeutic index by facilitating increased dose intensification while maintaining a predictable and manageable safety profile.

Liposomes as nanomedical devices

“…This effect is a consequence of a lower clearance and a higher area under the curve compared with conventional free vincristine sulfate. 65 In the field of antimicrobial agents, liposomal amphotericin B showed better tolerance and higher efficacy than the antibiotic amphotericin B deoxycholate. At present, liposomal amphotericin B is the drug of choice for the treatment of patients with disseminated histoplasmosis and acquired immunodeficiency syndrome (AIDS).…”

NCCN Guidelines Insights: Acute Lymphoblastic Leukemia, Version 1.2017

“…71,72 VSLI was evaluated in an open-label, multicenter, phase II study in adult patients with Ph-negative ALL (n=65; median age, 31 years; range, 19-83 years) in second or greater relapse, or with disease that progressed after ≥2 prior lines of therapy (RALLY study). 73 The CR (CR + CRi) rate with single-agent VSLI was 20%.…”

Pharmacokinetic Behavior of Vincristine and Safety Following Intravenous Administration of Vincristine Sulfate Liposome Injection in Chinese Patients With Malignant Lymphoma

“…Vincristine sulfate liposome injection (VSLI) is an encapsulated preparation of standard VCR in liposomes, which was designed to overcome the dosing and PK limitations of conventional vincristine sulfate injection (VSI). VSLI has been studied extensively both in laboratory (Kanter et al, 1994; Webb et al, 1995, 1998; Krishna et al, 2001; Zhong et al, 2014; Shah et al, 2016a) and in the clinic (Embree et al, 1998; Gelmon et al, 1999; Bedikian et al, 2006, 2011; Rodriguez et al, 2009; Thomas et al, 2009; Yan et al, 2012; Silverman et al, 2013; Douer, 2016; Shah et al, 2016b) to show the superiority over standard VCR. Marqibo ® (Hana Biosciences, Inc.) was the first listed VSLI approved by FDA at 2012 (Silverman and Deitcher, 2013).…”