CELL KINETIC-DIRECTED SEQUENTIAL CHEMOTHERAPY WITH CYCLOPHOSPHAMIDE AND ADRIAMYCIN IN T1699 MAMMARY-TUMORS

  • 1 January 1980
    • journal article
    • research article
    • Vol. 40  (3) , 737-743
Abstract
The changes in [3H]deoxythymidine labeling index, primer-dependent DNA polymerase labeling index and S-G2 transition after treatment of T1699 tranplantable mouse mammary tumors with adriamycin (5 mg/kg) and cyclophosphamide (100 mg/kg) were studied. Treatment with these agents resulted in intervals of subnormal tumor cell proliferation as indicated by decreased [3H]deoxythymidine labeling index, primer-dependent DNA polymerase labeling index and S-G2 transition. Recovery, as indicated by increases in [3H]deoxythymidine labeling index, primer-dependent DNA polymerase labeling index and S-G2 transition, was observed 3 days after adriamycin treatment and 6-7 days after cyclophosphamide treatment. To evaluate the predictive nature of the kinetic changes for effective time sequencing, sequential combination chemotherapy protocols were designed and tested in T1699 tumor-bearing mice. The results from these studies showed that the most effective chemotherapy schedules were those in which the drugs were sequenced to coincide with the cell kinetic recovery from the single agents alone. These effective sequencing intervals were also effective when used in multifraction sequential combination chemotherapy protocols. Changes in cell kinetic parameters following drug perturbation can provide indications as to potentially efficacious and nonefficacious sequencing intervals.