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The physician\u2010scientist has, in turn, learned a great deal about normal and abnormal cellular biology by using these drugs as probes. The observations that certain tissues and certain tumors share patterns of drug toxicity have led to a broadening of biologic understanding and to the use of combinations of drugs with shared antitumor activity and unshared toxicities. This empiric art of cancer chemotherapy has resulted in great progress in the treatment of a large number of advanced cancers. As important, however, is that this experience has resulted in knowledge which is leading to the development of rationally designed therapeutic regimens; to drug analogues seeking greater therapeutic\u2010toxic ratios; to the development of methods for chemically interfering with toxic drug effects while allowing or enhancing antitumor effect; and to work defining effects of drug timing. Drug timing research considers drug dosage in respect to the timing of a drug relative to the timing of other drugs (drug\u2010time\u2010drug interactions) or to other doses of that same drug (drug\u2010drug interval); the order of drugs (drug\u2010drug sequence); and the timing of drugs relative to an internal organismic time structure (time\u2010drug interactions). Data in this brief review clearly show that drug timing needs to be considered when designing rational chemotherapy for a living organism suffering from a cancer. The beautiful spatiotemporal complexity of life is not to be ignored or avoided, but should be considered as a golden opportunity to use what few imprecise chemical weapons we have a little more effectively.<\/jats:p>","DOI":"10.1002\/aja.1001680407","type":"journal-article","created":{"date-parts":[[2005,2,27]],"date-time":"2005-02-27T03:06:50Z","timestamp":1109473610000},"page":"519-542","source":"Crossref","is-referenced-by-count":49,"title":["The clinical application of chronobiology to oncology"],"prefix":"10.1002","volume":"168","author":[{"given":"William J. M.","family":"Hrushesky","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,2,3]]},"reference":[{"key":"e_1_2_1_2_1","first-page":"441","article-title":"Studies of surface immunoglobulins on human b lymphocytes. III. 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