Effects of combined treatments of cis-diamminedichloroplatinum(II), 5-fluorouracil, and X-rays on growth of human cancer nodules maintained in continuous organotypic culture.

The effectiveness of combined treatments of cis-diamminedichloroplatinum(II) (cis-DDP), 5-fluorouracil (5-FUra), and X-rays on growth inhibition of human pulmonary cancer nodules maintained in continuous organotypic culture was tested. To obtain the most effective growth inhibition, a cis-DDP treatment had to be preceded by an X-irradiation, whereas a 5-FUra treatment had to be postirradiated. This indicates the importance of the order in which the different combinations must be done. A mixture of 5-FUra and cis-DDP was even more effective than the X-ray and drug combination but only for a short period of time; reduction of nodule size and cell loss occurred during the 2 weeks following the treatment. After this period, as happened also with nodules treated with 5-FUra alone, vigorous regrowth occurred after treatment with cis-DDP plus 5-FUra, and all the nodules regained the size of the controls sooner or later. It is to be noted that, if X-rays were applied after a 5-FUra treatment, this regrowth is inhibited at least up to 45 days after the treatment.