CELL-KINETICS AND CHEMOTHERAPY - CRITICAL-REVIEW

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  • 1 January 1978
    • journal article
    • review article
    • Vol. 62  (8) , 1117-1133
Abstract
Methods of studying cell kinetics in man, cell population kinetics of human tumors and bone marrow, drug interactions and the cell cycle, and possible applications to chemotherapy were reviewed. Cell cycle time and S-phase duration for proliferating granulocyte precursors in human bone marrow were poorly defined but were probably shorter than median values for most human tumors, including leukemia. Most drugs had greater toxicity for cycling cells and some variation in toxicity at different phases of the cell cycle. There is a special need for chemotherapy directed at slowly proliferating and hypoxic tumor cells. Pretreatment indices of tumor cell kinetics were of little value in choosing drugs or in predicting response. Experiments in animals demonstrated that the therapeutic index may depend on schedule. Knowledge of cell kinetics in animals rarely allowed prediction of the optimal schedule and is unlikely to do so in man. Optimal schedules in mice were not directly relevant to man. Measurement of tumor labeling index or DNA histogram by flow microfluorimetry to detect cell synchrony was of little benefit in scheduling if concurrent changes in bone marrow were ignored; these methods were invalid at short intervals after treatment because surviving clonogenic cells were indistinguishable from a larger number of drug-damaged cells prior to their lysis. The major factor determining the outcome of chemotherapy was the availability of drugs with activity for the tumor and acceptable host toxicity. Claims that complex schedules using several drugs are effective because of synchrony or kinetic differences of tumor and normal tissue are at present unsubstantiated.