The effect of timing of vincristine administration during a course of fractionated radiotherapy in a mouse carcinoma

It has been previously shown that the uptake of 3H-vincristine by the NT carcinoma tumour in CBA mice can vary by a factor of 3 during a course of fractionated radiotherapy (2 Gy day −1, 5 day week −1, for 5 weeks). Here the effect of therapeutic doses of vincristine given at times of either maximum or minimum uptake has been investigated. The results show that whereas vincristine alone has a dose-related effect on this tumour, when given in combination with fractionated radiation it is only effective if administered during the first few fractions. It does not seem to matter whether it is given at times of maximum or minimum uptake. It is concluded that vincristine either exacerbates the radiation-induced vascular damage so that drug extravasation is reduced or that it causes a shift in the time of appearance of the peaks and troughs of uptake. The possibility that radiation-induced resistance to vincristine may have played a part in the results is also discussed.