Timing of Therapies: Chronomodulation and Metronomic Dosing
Nancy Hepp, MS, BCCT Project Manager
Laura Pole, RN, MSN, OCNS, BCCT Senior Researcher
Last updated December 21, 2020.
Chronomodulation, or chronomodulated chemotherapy, involves administering chemotherapy drugs at optimal times of day when cancer cells may be more susceptible and/or when normal cells are less likely to be damaged by treatment. The intended outcome is to make treatment more effective with fewer side effects.
Integrative oncologist and BCCT advisor Keith Block, MD, has been a pioneer of chronomodulated chemotherapy in the United States. A brief excerpt from his description:
Gold standard research supports the use of chronomodulated chemotherapy. For example, for metastatic colon cancer patients, studies show that administering chemotherapy at the optimal time can halve toxicity and double treatment response. For advanced metastatic ovarian cancer, a study in the journal Cancer reported that optimal timing of chemotherapy can reduce toxic side effects by 50 percent and quadruple five-year survival. This is a four-fold improvement! (Four times as many patients were alive at the five-year mark). The same study demonstrated a 75 percent reduction in the need to cut the treatment dose!1
Practical obstacles may make administering chemotherapy based on chronomodulation less available. Giving drugs at odd times of the day or night (such as a colorectal cancer chemotherapy regimen of administration at 4am, 5am and 4pm) can be difficult to schedule, for example.2 US insurers may not reimburse for chronotherapy expenses.3
The patients' sex, genetic background, and lifestyle influenced responses and drug schedule tolerability4
Treating the Cancer
Working against cancer growth or spread, improving survival, or working with other treatments or therapies to improve their anticancer action
Evidence shows benefit with acute lymphoblastic leukemia, ovarian cancer, endometrial uterine cancer, metastatic colorectal cancer, metastatic transitional cell carcinoma, bladder cancer, progressive metastatic renal cell carcinoma, breast carcinoma, lung carcinoma, hormone-refractory metastatic prostate cancer and genitourinary tract cancer.
Lab and Animal Evidence
Managing Side Effects and Promoting Wellness
Managing or relieving side effects or symptoms, reducing treatment toxicity, supporting quality of life or promoting general well-being
- Reduced rate and severity of adverse reactions while achieving higher rates of complete and partial remissions compared to those getting continuous infusion chemo23
Gastrointestinal Side Effects
Lab and Animal Evidence
Low-Dose Metronomic Chemotherapy
Early research as well experience in clinical practice is finding that metronomic chemotherapy, administering prolonged, repetitive and more frequent low doses of chemotherapy drugs, has these advantages:
- Interferes with the ability of the cancer to create its essential blood supply
- Reduces the cancer’s ability to become resistant
In a 2019 scientific review article the authors state: “The evidence of metronomic chemotherapy for personalized medicine is growing, starting with unfit elderly patients and also for palliative treatment.”29 Other studies and reviews show benefit.30
BCCT plans to write a full summary on chronomodulated therapies. While our summary is in development, you can visit these sources:
- Medscape: 5 Things to Know about Chronotherapy
- Block Center for Integrative Cancer Therapy: When it comes to chemotherapy, timing’s everything
- Cancer Causes & Control: Chronotherapeutics: the relevance of timing in cancer therapy
Integrative Programs, Protocols and Medical Systems
For more information about programs and protocols, see our Integrative Programs and Protocols page.
- Block Center for Integrative Cancer Treatment: Chronomodulation
- Chan S, Rowbottom L et al. Does the time of radiotherapy affect treatment outcomes? A review of the literature. Clinical Oncology (Royal College of Radiologists (Great Britain)). 2017 Apr;29(4):231-238.
- Kobayashi M, Wood PA, Hrushesky WJ. Circadian chemotherapy for gynecological and genitourinary cancers. Chronobiology International. 2002 Jan;19(1):237-51.
- Mormont MC, Lévi F. Circadian-system alterations during cancer processes: a review. International Journal of Cancer. 1997;70(2):241–247.
- Gurdev Parmar and Tina Kaczor: Textbook of Naturopathic Oncology
- Block KI, Block PB, Gyllenhaal C: Integrative Treatment for Colorectal Cancer
- Danial E. Baker: Application of chronotherapy to the treatment of cancer: can changing the timing of drug administration influence efficacy and toxicity?
- EmpowHER: Keith Block: My Activity
- Henry Mayo Clinic: Keith Block: New Roads to Health: Life over Cancer
- Keith I. Block, MD: Life over Cancer: The Block Center Program for Integrative Cancer Treatment