Repopulation of tumour cells between cycles of chemotherapy: a neglected factor.

Repopulation of clonogenic tumour cells during fractionated radiation treatment is recognised as an important factor affecting local control. Given the longer intervals between cycles and longer total duration of treatment, the impact of repopulation is likely to be greater following chemotherapy. Limited data from experimental models suggest that, after chemotherapy, there is a 'lag period', followed by variable but rapid rates of repopulation of tumour cells, possibly accelerating between cycles. Modelling of these properties indicates that after the initial response, accelerated repopulation between cycles can lead to tumour regrowth without any change in the drug sensitivity of the tumour cells. The importance of repopulation may be comparable with that of intrinsic or acquired cellular resistance in determining the effective resistance of tumours to chemotherapy. Biological agents with rapid onset and short duration of action, which can selectively inhibit tumour-cell repopulation, administered between cycles of chemotherapy, might improve the therapeutic index.