Oncology is forever chasing ways to separate the enemy within from its surrounding tissue and reduce ghastly treatment side effects. Just as each of our cells has a circadian cycle, tumor growth is rhythmic. Some lymphomas see a peak in cell division late in the evening, whereas gut lining divides 23 times as much in the early morning as it does at night. In this case, chemotherapy in the evening targets the tumor while doing away with excruciating effects on healthy tissue. The point is that distance between healthy and diseased tissue does not have to be spatial if you can separate them in time.
These are large differences in toxicity and efficacy, applying to more than 30 common anti-cancer agents, as well as radiotherapy, and varying by more than 50 percent as a function of dosing time. Colorectal cancer and ovarian cancer patients with well-timed meds can tolerate much higher dosages of whole-body drugs like 5-FU and oxaliplatin, and still have lower side effects. As expected, survival rates reflect the change over conventional delivery.
To get this size of an effect—near doubling of anti-tumor activity and five-fold decreases in some adverse events—it's not enough to prescribe a generic time to everyone. Timing can vary among people by several hours; rather, the patient's circadian rhythms are measured and monitored to hit their individual treatment efficacy peaks.
The world expert on timed medicine—variously known as chronomodulated therapy or, more simply, chronotherapy—is French oncologist Francis Lévi. To avoid opening chemo clinics at all hours of night, Lévi enlisted a biomedical company to develop a new technology that could improve quality of life for anyone currently trudging into a clinic for treatment. Programmable-in-time pumps deliver drugs on a schedule at a patient's home, with no need for hospitalization. During late-stage cancer, though, circadian rhythms fall apart. At this point, quality of life deteriorates and chronomodulated therapy is not as effective.
“At the beginning, even the notion of circadian rhythms was considered to be astrology—the whole field!” remembers Lévi. “Now we have identified genes and proteins, and we know how they work, which has given the field a major credibility it did not have when I started.”
There is a surprisingly long lag time, however, between that scientific credibility and adoption by the medical community, particularly when the implications are so inconvenient. It's more than that, though. In over a decade of reporting on circadian rhythms, I've seen the language evolve—everyone loves the word “circadian,” for example, but to a medical ear, despite prevalence in cardiology, "rhythms" sounds a bit woo.
Messaging is going to be every bit as important as evidence in coming days. Because it’s not just cancer treatment that would have to be adjusted to get out of our static, 3-D mentality. The dosage of any drug is wildly approximate without a prescribed hour of administration, because all drugs undergo absorption, metabolism and elimination. And all of these processes are controlled by the circadian system—at the cellular level, the organ level, and in the body as a whole.