Bonfil R Daniel, Russo Daniela M, Binda M Mercedes, Delgado François M, Vincenti Marc
Laboratory of Fundación de Investigación del Cáncer at CEFYBO, Serrano 669, (C1414DEM) Buenos Aires, Argentina.
Urol Oncol. 2002 Jul-Aug;7(4):159-66. doi: 10.1016/s1078-1439(02)00184-9.
The aim of this report was to investigate the feasibility of systemic treatment of transitional cell carcinoma of the bladder with vinflunine (VFL), and to compare its activity in respect to vinorelbine (VRL). Exposure of MB49 murine bladder cancer cells to both drugs showed a higher chemosensitivity of the cells to VRL than to VFL (IC50 values of 60 nM and 400 nM, respectively). Pretreatment of MB49 cells with non-cytotoxic drug concentrations revealed an inhibition of control in vitro invasiveness of 40 to 70% (1-25 nM VRL) and 22 to 80% (1-100 nM VFL) (P < 0.0001, ANOVA). The intraperitoneal administration of the drugs twice a week for 4 weeks in C57B1/6 female mice revealed that VFL was very well tolerated, with a 8-fold increase in the maximum tolerated dose in respect to VRL (40 mg/kg and 4.8 mg/kg, respectively). The administration schedule was evaluated in C57B1/6 female mice inoculated transurethraly with 5 x 10(4) MB49 cells. Intravesical tumor incidence on day 21 was 0% and 17% in mice treated intraperitoneally with 20 and 10 mg/kg VFL respectively (P = 0.0017 and P = 0.0001, Fischer's Exact Test), contrasting with 75-83% obtained in all VRL-treated groups and Controls. All mice treated with 20 mg/kg VFL were still alive 60 days after intravesical MB49 tumor implantation, as well as 50% of those treated with 10 mg/kg VFL, while most of the remaining mice (Control and VRL-treated) died before day 32. These studies clearly demonstrate the activity of VFL against a murine bladder cancer model, with a favorable toxicity profile.
本报告旨在研究长春氟宁（VFL）全身治疗膀胱移行细胞癌的可行性，并比较其与长春瑞滨（VRL）的活性。将MB49小鼠膀胱癌细胞暴露于两种药物中，结果显示细胞对VRL的化疗敏感性高于VFL（IC50值分别为60 nM和400 nM）。用无细胞毒性的药物浓度预处理MB49细胞，结果显示对体外侵袭的抑制率为40%至70%（1 - 25 nM VRL）和22%至80%（1 - 100 nM VFL）（方差分析，P < 0.0001）。在C57B1/6雌性小鼠中每周两次腹腔注射药物，持续4周，结果显示VFL耐受性良好，其最大耐受剂量相对于VRL增加了8倍（分别为40 mg/kg和4.8 mg/kg）。在经尿道接种5×10⁴个MB49细胞的C57B1/6雌性小鼠中评估给药方案。在第21天，腹腔注射20 mg/kg和10 mg/kg VFL的小鼠膀胱肿瘤发生率分别为0%和17%（Fisher精确检验，P = 0.0017和P = 0.0001），而在所有VRL治疗组和对照组中该发生率为75% - 83%。在膀胱内植入MB49肿瘤后60天，所有接受20 mg/kg VFL治疗的小鼠以及50%接受10 mg/kg VFL治疗的小鼠仍然存活，而其余大多数小鼠（对照组和VRL治疗组）在第32天前死亡。这些研究清楚地证明了VFL对小鼠膀胱癌模型具有活性，且毒性特征良好。
