[Tests of the sensitivity of histologically characterized carcinomas of the ovary or corpus to 4-hydroperoxicyclophosphamide, amethopterine, mitopodozide and VM-26 sandoz, using the technique of primary culture (author's transl)].
Cells from three carcinomas of the uterine corpus and from 14 ovarian carcinomas have been cultured in vitro by the monlayer and sandwich methods. They were evaluated on the basis of morphological criteria after 24 hours of incubation with 4-hydroperoxicyclophosphamide, amethopterine, mitopodozide and VM-26 Sandoz, using two dose ranges in each case. The index of 3H-thymidine was determined by means of two parallel experiments. Later results concerning pharmacokinetics of the cyclophosphamide have lead us to apply the technique of primary culture. Owing to the long duration of the incubation period, the 4-hydroperoxicyclophosphamide with its secondary and degradation products can influence the greatest possible numbers of cells through several phases of the cell cycle, thus obtaining an approach to in-vivo kinetics. A concentration of substrate per unit of volume, higher than the actually in vivo expected, is to compensate the short half-life of 4-hydroperoxicyclophosphamide as well as the lack of the supply-function of current dynamics. 4-hydroperoxicyclophosphamide was the cytostatic agent with the largest range of effectiveness, followed by amethopterine, while the mitotic poisons mitopodozide and VM-26 Sandoz were less effective. The histology and degree of differentiating of the tumors as well as the proliferation rate are not correlated in a distinct manner with sensitivity to cytostatics. Pretreatment with cytostatics of with irradiation revealed no certain influence upon subsequent sensitivity to cytostatics.