Sir

In his Essay 'A change of strategy in the war on cancer' (Nature 459, 508–509; 2009), Robert Gatenby proposes that controlling a tumour's growth may be more efficient in the long term than trying to eradicate it. However, it could be some time before we can establish whether such a switch in treatment strategy is clinically beneficial.

To keep cancer in check, Gatenby suggests giving progressively lower doses of cytotoxic drugs, rather than the maximum-tolerated doses used in conventional chemotherapy to try to destroy the tumour.

In fact, oncologists have for several years been using daily low doses of drugs such as etoposide or cyclophosphamide to control tumours that do not respond to chemotherapy at higher doses, an approach called metronomic therapy. Robert Kerbel and Judah Folkman and their colleagues discovered the potential of metronomic chemotherapy for restricting tumour blood-vessel growth some ten years ago (see, for example, G. Klement et al. J. Clin. Invest. 105, R15–R24; 2000) and Isaiah Fidler and Lee Ellis have proposed that cancer is a chronic disease and should be treated as such (I. J. Fidler and L. M. Ellis Nature Med. 6, 500–502; 2000).

But despite some promising results in adult and paediatric oncology, this approach remains marginal and limited to patients in relapse, or to those for whom conventional treatment has failed. Perhaps this is because a metronomic strategy challenges the predicted success of conventional regimens based on dose intensity.

Paradoxically, many oncologists have adopted metronomic scheduling with blockbuster drugs such as Gleevec, Tarceva and Sutent — targeted therapies administered daily at low doses — even though no one really knows whether a classical regimen of higher doses every three weeks might prove more efficient.

Gatenby's idea of 'adaptative therapy', derived largely from mathematical modelling, is a tour de force. He may be paving the way for advocates of traditional chemotherapy, targeted therapies and metronomic strategies to work together in the patient's best interest. We hope that stakeholders will be prepared to test Gatenby's approach and to revisit the idea of treating cancer as a chronic disease.