Chronotherapy of colorectal cancer metastases

Chronotherapy has consisted in the adaptation of chemotherapeutic drug deli very to circadian (similar to 24-hour) rhythms. This can be achieved in ful ly ambulatory patients using multichannel programmable pumps. Up to similar to 1500 patients with metastatic colorectal cancer have been registered in one of 15 trials testing the relevance of this treatment method with 5-flu orouracil +/- leucovorin +/- oxaliplatin. Chronotherapy was shown as signif icantly less toxic and more effective than constant rate infusion in 2 cons ecutive multicenter trials. High efficacy and good tolerability permitted s econdary surgical resection of previously inoperable metastases, with appar ent survival improvement (3-year survival greater than or equal to 20%) and cures in some patients. This strategy is currently undergoing further test ing within the European Organization for Research and Treatment of Cancer. Nevertheless, combining chronotherapy with surgery of colorectal cancer met astases can be readily offered to patients as a safer therapeutic option fo r optimizing outcome.