Comparative investigations on the effect of different dose schedules of the phase-specific drug vincristine (VCR) on the proliferation kinetics of a solid experimental tumour.

The aim of the present investigation was to study the effect of a high bolus injection (1 X 2.1 mg) of vincristine (VCR) during the phase of tumour growth retardation at the 14th day after transplantation and to compare the findings with the results of single (1 X 0.35 mg) and repeated (6 X 0.35 mg) applications of this cytostatic drug. Furthermore, an attempt was made to induce a synchronization of tumour cell proliferation. It was found that the effect on the volume growth was very pronounced after the high bolus injection and the repeated application of vincristine compared with the single low dose of the cytostatic drug. A synchronization of the tumour cell proliferation by flow out of the mitotic block could not be demonstrated. On the other hand a modest simultaneous recruitment of previously non-cycling tumour cells into the cell cycle occurred in the periphery of the tumour after the high bolus injection. The repeated application and the high bolus injection of VCR increased the cytostatic effect, especially in the tumour centre, related to the more slowly proliferating tumour cell compartment.