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TIMING OF CHEMOTHERAPY AND RADIATION TREATMENTS

In the past decade researchers have discovered that the success of chemotherapy treatments is oftentimes directly influenced by a patient's circadian rhythm. The circadian rhythm is your natural 24 hour day-night cycle (unless you're an overnight worker, more on that later). A normal circadian rhythm, in which a person is awake by day and asleep by night, dictates the body's timing as to when it releases certain hormones, enzymes, and other substances to keep the body running in top form. Part of this rhythm involves the release of substances which help with body cell regeneration and this is what is so important when it comes to cancer: Just like normal body cells, cancer cells also need to regenerate themselves, especially when enduring the severe damage caused by the chemotherapy and radiation treatments used to destroy them. Researchers have found that if chemotherapy and radiation are given during the time of the circadian rhythm when these cancer cells are least able to repair themselves then they are more easily destroyed. This method of using one's circadian rhythm to determine the time of drug administration is known as chronobiology.

CHEMOTHERAPY TIMING

Dr. Yosef Yarden and his team of researchers at the Weizmann Institute of Science in Israel found that the body's normal day-time release of certain steroids would bind to the EGF1 receptors on cancer cells; this bonding effectively blocks chemotherapy agents from properly attaching to the cancer cells during this time. Using mice as their models, Dr. Yarden and his team discovered that administering chemotherapy agents during the sleep phase resulted in significantly smaller tumors after only one week, in comparison to the mice that were given the agent during their waking hours. And, not only were the sleep-treated tumors smaller, but they also showed less infiltration of blood vessels in the tumors, indicating the tumors were much weaker than the wake-treated tumors.

Other studies have shown that another factor in timing is due to the ebb and flow of certain enzymes throughout the 24 hour cycle which can affect the potency of chemotherapy agents. This enzyme system is known as nucleotide excision repair – its job is to repair particular kinds of DNA damage in body cells. Dr. Aziz Sancar and his research team at the North Carolina School of Medicine studied this problem and found the following: Using mouse models the team discovered that DNA repair occurred six times faster in the morning hours than in the evening hours. Dr. Sancar stated “ By hitting cancer cells with chemotherapy at a time when their ability to repair themselves is mimnimal, you should be able to maximize the effectiveness and minimize the side effects of treatment.” Since many chemotherapy agents work by causing DNA damage to the cancer cells, timing one's treatments to work when this enzyme is less active is a crucial element in beating the disease. 2

Due to the encouraging results of the animal models, human studies were performed to verify these findings in human patients. These results have likewise been encouraging. For example:

Chemotherapy agents in certain classes tend to be associated with optimal times to be given. This is where it's important to know which classes your chemotherapy agents are listed under. If you do not know this information do not hesitate to ask your oncologist. The general rule of thumb for some of the different classes is as follows:

The timing of other chemotherapy agents is currently being investigated. Working out a schedule which works with your circadian rhythm may help your chemotherapy agents work harder and better for you, with the added bonus that common side effects associated with these agents tend to be less severe.


RADIATION TIMING

Just as the timing of chemotherapy is important to a patient's treatment, the timing of one's radiation therapy can likewise be important, though in a different way: Radiation treatment will kill the cancer cells no matter what time of day it is given, however, the time of day does make a difference when it come to experiencing side effects from the treatment. Here are a few examples:

Hair Loss: In 2013 the Salk Institute published findings that the correct timing of radiation therapy may reduce hair loss in cancer patients. Using mouse models, researchers found that mice who underwent radiation therapy in the morning lost 85% of their hair, whereas mice who underwent radiation therapy in the evening lost only 17% of their hair. It was noted that repair of cells in hair follicles occured during the evening, resulting in lower hair loss as the follicles could repair the damage immediately.

Diarrhea: The circadian rhythm also plays a part in the severity of mucositis (sores in the mucous membranes of the digestive tract) in cancer patients receiving radiation treatments. A study involving 229 patients with cervical cancer were divided into two groups. One group received radiation therapy in the morning (8am - 10am), the other in the evening (6pm - 8pm). Results showed that patients receiving the morning radiation experienced significantly higher rates of diarrhea than those receiving the evening treatments. (Pragya Shukla, et al, 2010).

Heart Risk: Radiation to the chest (especially the left breast) given between 6am - 12pm has been associated with increase risk of heart injury, sudden death from coronary artery spasms, and coronary artery disease 10-12 years after treatment. (Deepak Gupta, et al, 2012)

Mouth Sores: In a study involving 216 patients treated with radiation for head and neck cancers it was observed that those who received treatment in the morning (8am-10am) experienced less mouth sores and weight loss than those who received evening treatment (4pm - 6pm). (Georg A. Bjarnason, et al, 2009).

However, some patients are treated with a combination of both radiation and chemotherapy. It may be tempting for a patient to want to have both treatments concurrently (might as well hit the cancer with both shots when it's most vulnerable, right?). Although this can be a good strategy you need to be careful; some concurrent treatments increase the risk of organ damage. For example, it has been found that concurrent treatment with the chemotherapy agent tamoxifen along with radiation in hormone-fueled breast cancers tend to increase the risk of lung damage, and concurrent treatment of carboplatin and radiation increases the risk of kidney damage. In such cases you should have your chemotherapy and radiation therapy at separate times. In other cases, however, treatment works better when chemo and radiation are taken concurrently (ex. aromatase inhibitors with radiation), and so you should want them at the same time. Be sure to have a thorough discussion with your prescribing phyisician and radiologist to decide whether concurrent treatment is right for you.

 

OVERNIGHT WORKERS

Working the overnight shift is not avoidable for many people. We need people to work overnight shifts: Emergency doctors and nurses, police, firemen, overnight nursing homes and hospital staff, etc. -- we cannot live without them. Unfortunately though, these overnight staffers are working against their circadian rhythms in order to perform their lifesaving jobs, and this makes cancer treatment much more difficult.

Evidence is strong that a chronic disruption of one's circadian rhythm increases the risk of developing cancer, especially breast cancers (and this does include men as well). Not only does this situation increase the risk of cancer, but disrupted circadian cycles may cause the cancer to be more resistant to treatment. For example, a team of researchers from the Tulane University School of Medicine found that disturbed circadian rhythms cause breast cancer patients to be more resistant to the chemotherapy agent tamoxifen due to the disruption of melatonin production. Melatonin is an important hormone that is stimulates Natural Killer cells (NK) against cancer and helps reduce the side effects brought on by radiation and chemotherapy.

If you are an overnight worker and find yourself fighting cancer you need to establish a proper circadian rhythm in order for your treatments to work more effectively. To do this, you may opt to switch your work schedule hours to day shift (not evening or overnights) during your course of treatments so you can keep to the natural day-night cycle necessary for fighting the cancer. If your situation does not allow for this change then you need to simulate the natural day-night cycle necessary for a proper circadian cycle. This can be achieved by the following:


* On your way home in the morning, after your shift is finished, wear sunglasses. The shade of the sunglasses cues your body begin preparing for "sleep mode."
* When you arrive home get into a bedtime routine: Change into your pajamas, brush your teeth, and relax. This is not the time to do housework, catch up on phone calls, or other duties.
* Establish a solid bed time (8 or 9am sharp, if that works for you) and stick to it. Sleep in a darkened room for eight hours of the day. This means darkening your bedroom with black shades and dark curtains, even taping the sides to the wall to prevent sunlight from "leaking" in.
* Do not use any lights while you sleep. Studies have shown that something as simple as a night light or a brightly lit alarm clock can interfere with your sleep enough to make a difference in your health. If you must, turn your clock face away from you.
* Do not consume any caffeinated beverages for at least six hours before your established bed-time. Also, do not eat a heavy meal at least two hours before bedtime, as these can also disrupt a healthy sleep pattern.
* During your waking hours keep your environment as fully lit as possible. Do not use dimmed or low lighting if it is not absolutely necessary.


As a long time night-shifter myself I realize that keeping this kind of schedule can be challenging because life does not run on a night-shifter's schedule: Kids still need to get ready for school, doctor's appointments need to be kept, and other businesses (such as car repair services, etc.) do not run on a 24 hour basis. Do not let this discourage you though, as sometimes you may be able to work around some of these obstacles. For example, in some cases you can schedule your doctor appointments on your days off, in which case you can augment your sleeping habit to accommodate this (In many cases medical offices have extended hours in which you can be more easily accommodated; ask your practitioner). In some cases you may be able to enlist family, friends, or neighbors to help see your kids to or from school while you go through your cancer treatments. Also, keep in mind that many schools and churches have after-school children's programs your children may attend; these are opportunities which may help accommodate your day-sleep pattern. If you are able to, make your other repair appointments and such at times that are either very early in the day or very late so you can still sleep most of your day-time schedule.

I realize that you may not be able to work around all of your scheduling obstacles, however this does not mean you should just throw in the towel. Simply do your best to keep as much a routine as possible during the times that you can.

And one final note: Keep in mind that if you are using chemotherapy while working night shift you need to augment the timing of administration of the chemotherapy agents to match with your newly-established circadian rhythm since you will be living opposite hours than the day-shift population. Speak with your oncologist to establish a good timing with your overnight lifestyle.

 

1 EGF = Epidermal Growth Factor, a protein which stimulates cell production.

2 Ongoing research is needed to confirm whether DNA repair may be different between normal cells and cancerous cells, as well as the differences among the various cancers themselves. In many cases slow growing tumors tend to be more synchronized with the normal circadian rhythm and fast growing tumors tend to deviate from the normal rhythm.

3 “Stability” denotes that, although some cancer is still detected, it does not increase or spread.