Interaction between vinblastine and ionizing radiation in the mouse MO4 fibrosarcoma in vivo

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.