Van Belle S, Fortan L, De Smet M, De Neve W, Van der Elst J, Storme G
Academic Hospital, Brussels Free University, Department of Radiotherapy, Belgium.
Anticancer Res. 1994 May-Jun;14(3A):1043-8.
The effect of combining vinblastine (VLB) and ionizing radiation (IR) on tumor response was investigated in CDF1 mice bearing the MO4 mouse fibrosarcoma. Favorable interactions were assumed to occur if VLB treatment caused accumulation of cells in metaphase (M-)phase at the time of IR. High pressure liquid chromatography (HPLC) measurements showed that VLB administered at 2.0 mg/kg (0.4 maximal tolerated dose, MTD) was taken up rapidly by the tumor in vivo, and that sufficient concentrations of VLB were achieved to cause blocking of tumor cells in M-phase. However, different treatment schedules of the combination of 2.5 mg/kg VLB (0.5 MTD) and 10 Gy IR resulted in additive tumor responses. The best therapeutic response was observed when IR was given 6 hours after intravenous injection of VLB. In order to increase the therapeutic response, we attempted to enhance the accumulation of cells in M-phase by treating mice with VLB at the MTD. The maximum percentage of tumor cells that could be accumulated in mitosis by a single intravenous bolus of VLB at the MTD was around 13%. The results show that this will probably be insufficient for significant IR enhancement.
在携带MO4小鼠纤维肉瘤的CDF1小鼠中，研究了长春碱（VLB）与电离辐射（IR）联合使用对肿瘤反应的影响。如果VLB治疗在IR照射时导致细胞在中期（M期）积累，则假定会发生有利的相互作用。高压液相色谱（HPLC）测量表明，以2.0mg/kg（0.4最大耐受剂量，MTD）给药的VLB在体内被肿瘤迅速摄取，并且达到了足以使肿瘤细胞停滞在M期的浓度。然而，2.5mg/kg VLB（0.5 MTD）与10 Gy IR联合使用的不同治疗方案导致了相加的肿瘤反应。当在静脉注射VLB后6小时给予IR时，观察到最佳治疗反应。为了提高治疗反应，我们试图通过以MTD剂量用VLB治疗小鼠来增强细胞在M期的积累。在MTD剂量下，单次静脉推注VLB可使处于有丝分裂期的肿瘤细胞的最大百分比约为13%。结果表明，这可能不足以显著增强IR的效果。
