The influence of intra-arterial infusion of cisplatinum and bleomycin on the cell cycle in uterine cervical carcinoma.

We examine the influence of CDDP and BLM on the cell cycle in the patients with uterine cervical cancer. Specimens were obtained from 8 cases of local recurrent uterine cervical cancer which were treated with CDDP and BLM bolus infusions into bilateral internal iliac arteries. Except for two patients who showed no response according to the criteria of the National Cancer Institute (NCI), the other patients exhibited partial response (PR). The concentrations of BLM and CDDP were 0.83 +/- 0.05 microgram/g and 2.9 +/- 0.54 microgram/g in the tumor tissues 24 hours after treatment. The peak values of the drug concentrations in serum, which were observed at 30 min for both drugs, were 0.92 +/- 0.12 microgram/ml BLM and 1.02 +/- 0.65 microgram/ml CDDP and the concentrations of the drugs decreased rapidly in the serum. The higher levels of CDDP and BLM were retained in the tumor tissue 24 hours after treatment, than in serum. Changes in DNA content determined by flow cytometry, revealed that proliferation indices (PI) increased after treatment only in PR cases. The mean increase in the ratio was 0.10 +/- 0.015. The BrdU staining showed that cells in S phase increased in tumor tissues. Labeling indices increased from 0.10 +/- 0.04 to 0.18 +/- 0.05. These results suggested that cell synchronization was induced by CDDP and BLM in vivo. PI seemed a useful parameter for measuring drug sensitivity.