Cell Kinetic-Directed Sequential Chemotherapy with Cyclophosphamide and Adriamycin in T1699 Mammary Tumors

Paul G. Braunschweiger, Lewis M. Schiffer

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

The present studies were initiated to investigate the changes in [3H]deoxythymidine labeling index, primer-dependent DNA polymerase labeling index, and S-G2 transition after treatment of T1699 transplantable mouse mammary tumors with Adriamycin (5 mg/kg) and cyclophosphamide (100 mg/kg). 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 to 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 found to be effective when used in multifraction sequential combination chemotherapy protocols. The results suggest that changes in cell kinetic parameters following drug perturbation can provide indications as to potentially efficacious as well as nonefficacious sequencing intervals.

Original languageEnglish (US)
Pages (from-to)737-743
Number of pages7
JournalCancer Research
Volume40
Issue number3
StatePublished - Mar 1 1980

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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