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Because tumours regrow fastest when small, the best way to finish them is to give the same chemotherapy doses closer together. The idea, from Larry Norton and Richard Simon, was proved in breast cancer by the CALGB 9741 trial and made two-weekly chemotherapy a standard.
Norton and Simon argued in 1977 that chemotherapy kills tumour cells in proportion to the tumour's growth rate at that moment, and, since Gompertzian growth is fastest in small tumours, the residual disease after each cycle regrows quickly between cycles. Shortening the interval rather than raising the dose should therefore improve cure rates. CALGB 9741 (2003) tested two-weekly against three-weekly adjuvant chemotherapy with growth factor support in node-positive breast cancer and found better disease-free and overall survival, establishing dose-dense scheduling; the Early Breast Cancer Trialists' meta-analysis later confirmed a survival gain across trials.
Kill rate is proportional to the Gompertzian growth rate of the tumour, so regrowth between cycles is the enemy and shorter intervals matter more than higher doses.
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Shares Gompertzian tumour growth, Mathematical models of cancer (mathematical oncology), Cytotoxic chemotherapy and the tag mathematical-model.
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