Vincristine sulfate liposomes injection (Marqibo) in heavily pretreated patients with refractory
Cancer. 2009 Aug 1;115(15):3475-82.
Vincristine sulfate liposomes injection (Marqibo) in heavily pretreated patients with refractory aggressive non-Hodgkin lymphoma: report of the pivotal phase 2 study.
Rodriguez MA, Pytlik R, Kozak T, Chhanabhai M, Gascoyne R, Lu B, Deitcher SR, Winter JN; Marqibo Investigators.
Source Lymphoma/Myeloma Department, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. email@example.com
Marqibo, a sphingosomal/cholesterol encapsulation of vincristine sulfate has targeted, increased, and sustained delivery of vincristine to tumor tissues. A phase 2, open-label, single-arm, and multinational study evaluated the efficacy and tolerability of Marqibo as a single agent in patients with multiply relapsed or refractory aggressive non-Hodgkin lymphoma (NHL).
METHODS: Eligible patients had relapsed or refractory de novo or transformed aggressive NHL and prior treatment with at least 2 multiagent chemotherapy regimens. Marqibo was administered at 2 mg/m2, every 2 weeks, for a maximum of 12 cycles or until toxicity or disease progression.
RESULTS: One hundred and nineteen patients were enrolled and treated on trial. Ninety-six had histological confirmed de novo (N=89) or transformed (N=7) aggressive NHL. Median number of cycles was 4 (median dose/cycle 4 mg). Overall response (CR and complete response unconfirmed and PR) was 25% (95% confidence interval [CI], 17, 35), CR and complete response unconfirmed confirmed by external reviewers was 5%. Median overall survival was 6.6 months (Kaplan-Meier estimate, 95% CI, 4.7, 9.8). Grade 3 of 4 neurotoxicity occurred in 32% of patients. All patients had prior neurotoxic agents, and 85% had baseline residual neuropathy symptoms (grades 1-2) from prior treatment.
CONCLUSIONS: Marqibo is an active agent in patients with heavily pretreated aggressive NHL, and tolerated at approximately twice the dose intensity of standard vincristine. Its activity supports further investigation as a substitution for vincristine in combination treatment of lymphoid disorders.
Enhanced therapeutic effects on the multi-drug resistant human leukemia cells in vitro and xenograft in mice using the stealthy liposomal vincristine plus quinacrine.
Liang GW, Lu WL, Wu JW, Zhao JH, Hong HY, Long C, Li T, Zhang YT, Zhang H, Wang JC, Zhang X, Zhang Q.
Source State Key Laboratory of Natural and Biomimetic Drugs and School of Pharmaceutical Sciences, Peking University, Beijing 100083, China.
Abstract The multi-drug resistance (MDR) could be caused by the over-expression of adenosine triphosphate binding cassette transporters such as p-glycoprotein, thereby resulting in the efflux of anti-cancer drugs from the cells. An anti-resistant stealthy liposomal vincristine plus quinacrine was defined in this study. Human chronic myelogenous leukemia K562 and MDR K562 cells were included for comparisons. Anti-tumor activity studies were performed on female BALB/c nude mice with MDR K562 cell xenografts. Results showed that quinacrine was effective in reversing the resistance in the MDR K562 cells, and enhanced the anti-tumor effect of vincristine in K562 cells. The caspase-9 and -3 activities in the MDR K562 and K562 cells were increased with the dose rise of quinacrine. In the MDR K562 cell xenografts in mice, the anti-resistant tumor effect of the stealthy liposomal vincristine plus quinacrine was evidently observed. The enhanced anti-tumor effects of vincristine by quinacrine in the resistant/non-resistant K562 cells could be because of the direct injury and the potentiating apoptotic effect of vincristine via activating the initiator caspase-9 and subsequently the effector caspase-3, and the long circulatory effect of stealthy liposomes. The stealthy liposomal encapsulation of vincristine plus quinacrine could be a potential therapeutic approach for resistant human leukemia.