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Chemotherapy Disrupts Biological Clock
According to research, chemotherapy disrupts biological clock in patients undergoing therapies. While the research linked below makes this blanket statement for ALL cancer survivors, I have tried to focus this issue for MM patients and survivors.
Which chemotherapy regimens used in myeloma can disrupt the patient’s circadian rhythms?
circadian rhythm disruption in myeloma patients isn’t often discussed, but it can be an important source of fatigue, sleep disorders, and immune dysregulation. Chemotherapy regimens can affect circadian rhythms in two main ways:
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Direct pharmacologic effects on the central circadian clock (suprachiasmatic nucleus) or peripheral clocks (in liver, immune cells, etc.).
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Indirect effects via corticosteroids, sleep disturbance, metabolic changes, or timing of administration.
Here’s a breakdown for multiple myeloma regimens:
Regimens with the highest circadian disruption potential
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Steroid-heavy regimens (included in almost all myeloma combinations):
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Dexamethasone is the most circadian-disruptive drug in myeloma care.
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It alters cortisol rhythms, suppresses melatonin, and causes insomnia, mood swings, and nighttime alertness.
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Long-term use can flatten diurnal cortisol secretion and impair sleep-wake cycles.
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Regimens where dexamethasone is given in high weekly doses (e.g., VRd, KRd, Dara-Rd, Elo-Rd, VCd, DVd, etc.) are particularly disruptive.
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VAD regimen (Vincristine, Adriamycin/doxorubicin, Dexamethasone):
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Vincristine is neurotoxic and disrupts autonomic and peripheral nerve signaling, which can impact circadian cues.
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Doxorubicin is known to interfere with circadian gene expression in cardiomyocytes and other tissues.
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High-dose dexamethasone adds to circadian misalignment.
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Other regimens with circadian impact
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Alkylators (Melphalan, Cyclophosphamide, Bendamustine):
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Cause DNA damage that interacts with circadian-regulated DNA repair pathways.
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Can indirectly disturb rhythms via nausea, fatigue, and disrupted sleep.
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Cyclophosphamide, in particular, has been studied in chronotherapy — its toxicity varies depending on time of day given, highlighting its circadian interaction.
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Anthracyclines (Doxorubicin in VAD):
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Strong circadian toxicity profile — animal studies show cardiac toxicity and survival vary with dosing time.
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Targeted agents and circadian effects
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Proteasome inhibitors (Bortezomib, Carfilzomib, Ixazomib):
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Less direct circadian disruption, but they can cause neuropathy, GI upset, and fatigue that secondarily disturb sleep.
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Preclinical studies suggest proteasome inhibition interacts with circadian regulation of protein degradation, though not clearly translated into sleep disruption clinically.
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IMiDs (Lenalidomide, Pomalidomide, Thalidomide):
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Can cause insomnia, restless legs, or sedation depending on patient.
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Less direct disruption than steroids, but still capable of altering sleep quality.
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✅ Summary:
The biggest circadian rhythm disruptors in myeloma therapy are dexamethasone-containing regimens and anthracycline-based regimens (VAD), with additional indirect effects from alkylators and IMiDs. Proteasome inhibitors play a smaller role but can contribute through side effects.
Possible solutions?
- Take dexamethasone first thing in the morning.
- Exposure to bright light first thing in the morning.
- Take melatonin, 2–5 mg taken 1–2 hours before bedtime.
- Consistent sleep/wake time.
- Time-restricted eating.
- Regular moderate exercise.
- Mind-body therapies.
While fatigue may not always result from lack of sleep, it is one of the, if not the most common side effect of treatment. So a good night’s sleep or a regular circadian rhythm, would be a great start to alleviate fatigue.
I am an MM survivor and cancer coach. Email me at David.PeopleBeatingCancer@gmail.com to learn more about managing your MM with both conventional and non-conventional therapies.
Good luck,
David Emerson
- MM Survivor
- MM Cancer Coach
- Director PeopleBeatingCancer
Exploring whether chemotherapy disrupts biological clock in the brain to impair circadian rhythms
During and after chemotherapy, nearly half of cancer patients endure circadian rhythm disruptions, which worsens treatment side effects. Because the body’s primary rhythm pacemaker is in the brain, this suggests that perhaps chemotherapeutics target the brain to disrupt circadian rhythms.
However, research shows that cancer treatments do not penetrate the brain well. To shed light on this discrepancy, researchers led by Leah Pyter at Ohio State University explored whether paclitaxel, a frequently used breast cancer treatment, disrupts the biological clock in the brain to impair circadian rhythms.
In their eNeuro paper, the researchers used a paclitaxel treatment regimen on mice and measured molecular and behavioral changes linked to biological clock functioning. They examined only female mice because breast cancer primarily affects women. The expression of circadian rhythm-related genes in the primary biological clock did not fluctuate throughout the day in treated mice, which was irregular. Because light is the most important cue for the pacemaking function of this brain region, the researchers assessed how different light challenges influenced biological clock-mediated behavioral adaptations. Mice undergoing chemotherapy did not adapt as well to these challenges.
Thus, paclitaxel may disrupt both molecular and behavioral rhythm outputs of this pacemaker brain region. Says first author Zoe Tapp, “The idea that the principal part of the circadian clock in the brain isn’t directly targeted by paclitaxel but is still affected by treatment was new and interesting to see.”
Speaking on potential clinical implications of this work, says Pyter, “Linking the circadian rhythm disruption that patients complain about to the side effects of chemotherapy that cause quality-of-life issues more solidly may be an important next step.
It’s possible that giving cancer patients obvious information about ‘day’ and ‘night’ and proper circadian rhythm maintenance could reduce side effects during treatment. But we would need to show that circadian rhythm brain pathways are affected by chemotherapy for this to happen.”
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