[Experimental study of chemotherapy of renal cell carcinoma. 1. Combination effect through the use of cell kinetics-directed treatment schedules].

To establish a useful combination chemotherapy of advanced renal cell carcinoma, I determined the optimal design of therapeutic schedules with an in vitro experimental model. At first, I determined the chemosensitivity of the NC-65 cell line established from human renal cell carcinoma. The method used is an original growth inhibition test which traces the cell growth in the same area by photography. This method can be completed in a short term and cell growth inhibition rate evaluated sequentially and precisely as well. Among 8 tested drugs, vincristine (VCR), adriamycin (ADM) and carboquone (CQ) were the most effective drugs. The effect of these three drugs on cell cycle traverse was estimated by flow cytometry. With all of these three drugs, at a concentration which inhibits cell growth less than 50%, an accumulation of cells in the S and G2-M phases was observed 12 hours after the exposure to the drugs. Although 24 hours later, the histogram showed the increase in cells of a G1 phase and decrease in G2-M cells, followed by the cell progression partially synchronized. The tendency was the most characteristic in VCR although it was not so significant in CQ. Effectiveness of the simultaneous or sequential combination of two-drugs was compared to the calculated expected effect using the t-test. At a low concentration which inhibits cell growth 32% (IC 32), most of the combination groups showed a weak effect. Sequential treatment at 12-hour intervals such as with VCR-ADM, CQ-VCR, CQ-ADM, were considered more effective than that of a 24-hour interval. In the medium concentration which inhibits cell growth 50% (IC 50), simultaneous administration of ADM and CQ showed a relatively high inhibition rate. Sequential treatment of CQ followed by VCR was the most cytotoxic. Comparison of sequential administration schedules, administration at 12-hour intervals showed a higher inhibition rate than that of a 24-hour interval, in the combination of VCR-ADM, CQ-ADM.