Dataset Information

Efficacy and Safety of Vincristine Sulfate Liposome Injection in the Treatment of Adult Acute Lymphocytic Leukemia.

ABSTRACT: : Acute lymphoblastic leukemia (ALL) is a heterogeneous group of hematologic malignancies that arise from clonal proliferation of immature lymphoid cells in the bone marrow, peripheral blood, and other organs. The vinca alkaloid vincristine is a standard component of chemotherapy regimens used to treat ALL, because of its well-defined mechanism of action, demonstrated anticancer activity, and ability to be combined with other agents. However, the dosage of vincristine is frequently capped because of neurotoxicity concerns, and patients with large body surface areas are, therefore, almost always underdosed. Liposomal formulations have the ability to "passively" accumulate at sites of increased vasculature permeability and reduce the adverse effects of encapsulated relative to free drug. Vincristine sulfate liposome injection (VSLI) is a sphingomyelin/cholesterol-based liposome-encapsulated formulation that is delivered weekly in a 1-hour infusion. Based on the pharmacokinetics of the liposomal delivery system, vincristine is slowly released from the liposome and delivered into the tissues more efficiently than with the standard preparation, allowing a higher dose. This increase in therapeutic index from reduced toxicity is a valuable difference between the two formulations. VSLI is indicated for the treatment of adults with second or greater relapse and clinically advanced Philadelphia chromosome-negative ALL. For the first time, studies will be able to exploit the delivery of higher and uncapped doses of vincristine in randomized studies comparing first-line chemotherapy with standard vincristine versus VSLI in both ALL and lymphoma to determine whether VSLI is superior to conventional vincristine.This review summarizes the development of vincristine sulfate liposome injection, a new formulation of vincristine. The pharmacokinetics of liposomal drug delivery are examined, the limitations and advantages of conventional and liposomal vincristine are compared, and the use of vincristine sulfate liposome injection in clinical trials and case studies is included. Clinicians will be informed of a new chemotherapy agent that is indicated for the treatment of adults with Philadelphia chromosome-negative acute lymphoblastic leukemia, whose disease has relapsed two or more times or whose leukemia has progressed after two or more regimens of antileukemia therapy.

SUBMITTER: Douer D

PROVIDER: S-EPMC4943385 | biostudies-other | 2016 Jul

REPOSITORIES: biostudies-other

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Efficacy and Safety of Vincristine Sulfate Liposome Injection in the Treatment of Adult Acute Lymphocytic Leukemia.

Douer Dan D

The oncologist 20160621 7

<h4>Unlabelled</h4>: Acute lymphoblastic leukemia (ALL) is a heterogeneous group of hematologic malignancies that arise from clonal proliferation of immature lymphoid cells in the bone marrow, peripheral blood, and other organs. The vinca alkaloid vincristine is a standard component of chemotherapy regimens used to treat ALL, because of its well-defined mechanism of action, demonstrated anticancer activity, and ability to be combined with other agents. However, the dosage of vincristine is frequ ...[more]

PMID: 27328933

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Project description:Objective: This phase Ia study was designed to assess the pharmacokinetic (PK) characters of free vincristine (F-VCR, refer to as non-liposomal VCR and VCR released from liposome) and total vincristine (T-VCR, the sum of both liposomal VCR and F-VCR), urinary excretion and safety of intravenous administration of vincristine sulfate liposomes injection (VSLI) in Chinese patients with malignant lymphoma and compare the results with those for conventional vincristine sulfate injection (VSI). Methods: In the phase Ia, randomized, open-label, two sequence cross-over study, patients from one group were exposed to treatment 1 including cytoxan (cyclophosphamide power injection), hydroxyrubicin (adriamycin power injection), oncovin (VSI), and prednisone tablets (standard CHOP scheme) before crossed over to treatment 2 (modified CHOP scheme in which VSI was replaced with VSLI). Patients from another group received treatments in reverse order. Results: In this phase Ia study, a total of eight subjects participated. VCR elimination from the circulation after injection of VSLI was characterized by a significantly increased maximum concentration (Cmax, 86.6 ng/mL) and plasma area under the plasma concentration-time curve from zero to infinity (AUC0-Inf, 222.1 ng/mL h), markedly decreased distribution volume (Vz, 224.1 L) and plasma clearance (CL, 8.9 L/h) compared to lower Cmax (26.6 ng/mL) and AUC0-Inf (95.1 ng/mL h), larger Vz (688.8 L) and CL (22.1 L/h) for VSI. The small proportion of F-VCR following infusion of VSLI in circulation was reflected by very low Cmax (1.8 ng/mL) and AUC0-Inf (50.5 ng/mL h). Less than 3% of the administered dose of VSLI was excreted in urine and the extent was similar to that for VSI. The elimination percentage of 40-21-14% for VSI changed to 6.2-24-39% for VSLI at intervals of 0-5, 5-13 and 13-25 h, respectively. Significant difference of toxicity between VSLI and VSI was not observed. Conclusion: VSLI exhibits higher AUC0-Inf of T-VCR, lower CL and Vz compared with VSI. VSLI was well tolerated, maybe due to the markedly decreasing AUC0-Inf of F-VCR. The majority of VCR was enveloped in liposome and VCR was released gradually from liposome following injection of VSLI. Liposomal encapsulation of VCR does not alter the route and extent of VCR excretion in urine.

Dataset Information

Efficacy and Safety of Vincristine Sulfate Liposome Injection in the Treatment of Adult Acute Lymphocytic Leukemia.

Publications

Efficacy and Safety of Vincristine Sulfate Liposome Injection in the Treatment of Adult Acute Lymphocytic Leukemia.

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