Cancer Chronotherapy

What is cancer chronotherapy?

Cancer chronotherapy involves giving chemotherapy at specific times of day or night. This approach is based on delivering chemotherapy when cancer cells are active and dividing. The times of day or night when this occurs relates to the circadium rhythms, or the body's biological clock, which orchestrate drug metabolism and cellular functions within 24-hour activity patterns.

What are the potential benefits of cancer chronotherapy?

Cancer chronotherapy has the potential to kill more active, dividing cancer cells and be less toxic to healthy cells. This optimal timing of drug delivery may also allow people with cancer to tolerate necessary chemotherapy doses that are too toxic otherwise. Timing chemotherapy may increase anti-cancer efficacy of cancer treatments and cancer survival as well as reduce cancer side effects^1-4.

Who is focused on cancer chronotherapy?

Currently, some cancer providers in the United States offering input about chronotherapy are Keith Block, MD of the Block Center in Evanston, Illinois and William Hrushesky, MD of the Veterans Administration Hospital in Columbia, South Carolina.

Many cancer centers in Europe offer chronotherapy.

What work is occurring in Europe to support research and delivery of cancer chronotherapy?

TEMPO, a European Union collaborative project focused on chronotherapy, refers to the important role of chronotherapy in reducing cancer side effects and improving therapeutic activity of cancer treatments.

"Differences in tumor molecular characteristics and in patient genotype, gender, age, lifestyle and circadian clocks account for large variability in the time course of cancer diseases and response to treatments. TEMPO addresses the control of several key dynamic pathways in cancer drug metabolism and cellular proliferation by the circadian timing system. This biological system consists of a network of molecular clocks which are coordinated by a brain pacemaker. As a result, the circadian timing system generates 24-hour rhythms in behavioral, bodily and cellular functions, through putting genes and proteins at work at the proper times of day or night, when their activity is anticipated to be most necessary. Circadian disruption occurs in tumors, and results in the deregulated proliferation of cancer cells.

Chronotherapeutics aim at the delivery of medications according to the 24-hour rhythms generated by the patient's molecular clocks in order both to prevent adverse events and to improve overall therapeutic activity. TEMPO aims at the personalization of the chronotherapeutic delivery pattern of anticancer drugs."

For More Information

• Life Over Cancer by Keith Block, MD
• Biological Rhythms in Cancer
• William Hrushesky, MD

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References:

1. Lévi F. The circadian timing system, a coordinator of life processes. implications for the rhythmic delivery of cancer therapeutics. Conf Proc IEEE Eng Med Biol Soc. 2006;Suppl:6736-9. Review. PubMed PMID: 1795949
2. Lévi F, Focan C, Karaboué A, de la Valette V, Focan-Henrard D, Baron B, Kreutz F, Giacchetti S. Implications of circadian clocks for the rhythmic delivery of cancer therapeutics. Adv Drug Deliv Rev. 2007 Aug 31;59(9-10):1015-35. Epub 2007 Jul 4. Review. PubMed PMID: 17692427.
3. Eriguchi M, Levi F, Hisa T, Yanagie H, Nonaka Y, Takeda Y. Chronotherapy for cancer. Biomed Pharmacother. 2003 Oct;57 Suppl 1:92s-95s. Review. PubMed PMID:14572683.
4. Kobayashi M, Wood PA, Hrushesky WJ. Circadian chemotherapy for gynecological and genitourinary cancers. Chronobiol Int. 2002 Jan;19(1):237-51. Review. PubMed  PMID: 11962679.