We’ve seen in previous blog posts that melatonin can have anti-cancer effects. But when should we give melatonin? Should it just be at night or can we give it during the day? Does timing matter? If so, should we consider the timing of other treatments too?

Does the timing of melatonin administration matter?

A paper published in 2014 by Cancer Treatment Centers of America [1] looked at this very question.  They studied the effect of melatonin in 84 patients with advanced non-small cell lung cancer (NSCLC).  There were three groups in the study:

1st group – treatment:  inert placebo at 8am and 8pm

2nd group – treatment: 20mg melatonin at 8am and the placebo at 8pm

3rd group – treatment: placebo at 8am and 20mg melatonin at 8pm

Overall, there was better survival in those receiving the melatonin in the evening. The relative risk of death was approximately half when patients had the evening melatonin (P=0.04, RR of death 0.454).  Partial shrinkage rate of tumors was 29.4% for the evening melatonin group compared to 7.7% for the morning melatonin group. Additionally, quality of life declined less rapidly and sleep quality was enhanced with evening melatonin use. 

The conclusion is that the timing of giving melatonin is important, with evening administration showing the best effects. 

This concept of how the timing of treatments can lead to different effects is called chronobiology or chronotherapy. There is actually quite a bit of research in this area not just for circadian rhythm altering products like melatonin, but for chemotherapy too. 

Chronobiology of chemotherapy  

Considering the chronobiology of chemotherapies helps in several different ways:

  1. Timing can allow targeting of the cancer cell metabolism when it is most sensitive, resulting in faster tumor shrinkage and remission.
  2. Many chemotherapies and cancer drugs need to be metabolized before they are effective, so timing needs to take this into consideration.
  3. Chemotherapies often work best in the presence of certain hormones. As hormonal levels vary according to circadian rhythms, so too will those treatments that are most effective if they coincide with hormonal levels.
  4. The timing of treatment might also affect the side effects of treatments. 

Chronomodulated chemotherapy

One of the key oncologists in this field is Dr Keith Block from The Block Center for Integrative Cancer Treatment.

At this facility, they use chronomodulated chemotherapy via portable computerized pumps to administer the drugs at the optimal time of the day. Patients wear this pump in a fanny pack around their waist, allowing them to be active during the day and maintain their activities. Dose levels and durations change depending on both the patient’s circadian rhythm and the nature of the cancer. 

Study findings for chronomodulated chemotherapy

Results of studies in this area show, for example, that antimetabolite chemotherapies like 5-FU work better and produce less side effects when given in the evening or at night [2]. This is because these drugs interfere with the synthesis of DNA. At night time, normal human cells slow DNA synthesis, but cancer cells do not. Thus, giving antimetabolite drugs at this time will lessen their effect on healthy cells and thus lower side effects.

 A review of patients with metastatic colon cancer found that chronomodulated chemotherapy halved the toxicity and doubled the treatment response[3]. Another review found that in patients with advanced metastatic ovarian cancer, optimal timing of chemotherapy quadrupled five-year survival rates, in addition to reducing toxic side effects by 50% [4].

Other studies in laboratory animals have found that thirty common cancer drugs have increased efficacy and lowered toxicity when the timing is controlled to match up with the body’s internal clock. Obviously not all cancer treatment facilities can do this, based on their schedules and practicalities. But, talk to your oncologist and see if they have information on chronomodulation and your cancer treatment, and whether you can incorporate this into your plan. Even if they can’t, you can at least take control of the timing of some of our supplements, like melatonin, to optimize chronobiology. 

References

[1].Lis, C., Levin, R.D., Grutsch, J.F., et al. 2014. Effect of evening melatonin on the survival of patients with advanced non-small cell lung cancer. J Clin Oncol, 32. 

[2]. Cure, H., Chevalier, V., Adenis, A., et al. 2002. Phase II Trial of Chronomodulated Infusion of High-Dose Fluorouracil and l-Folinic Acid in Previously Untreated Patients With Metastatic Colorectal Cancer. JCO, vol. 20 no. 51175-1181

[3]. Chronopharmacology and chronotherapy of cancers 1996. Pathol Biol (Paris), 44(7):631-44.

[4]. Circadian chemotherapy for gynecological and genitourinary cancers. 2002. Chronobiol Int., 19(1):237-51.

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