~ Treatments Aligned With Body's Clock May Work Better

Treatments Aligned With Body's Clock May Work Better

InsideVC.com, 07-20-06

The clock was ticking for Frank Fazio. By the time his colon cancer was discovered, the disease had spread to his abdomen, spine and bones.

But instead of undergoing conventional chemotherapy, Fazio, 64, literally tried putting time on his side. Using the little-known practice of chronotherapy, the Orland Park, Ill., housing contractor received chemo drugs based on the internal rhythms of his body and his illness.

It has been four decades since Western medicine began to acknowledge the existence of the mysterious 24-hour body clock, proteins found throughout the body that determine whether we're morning larks or night owls.

Although once considered entirely experimental, chronotherapy, or the practice of synchronizing medical treatment with body time, is now commonly used to treat everyday health problems, including sleep disorders, high blood pressure, asthma and arthritis.

The cutting-edge use of chronotherapy is in cancer treatment, particularly colorectal cancer, the second most common cause of cancer deaths in the United States behind lung cancer. Though still in its infancy, some studies suggest that chronotherapy can improve a drug's effectiveness while diminishing side effects and toxicity.

Both chemotherapy and chronotherapy use the same powerful and poisonous drugs to kill cancer cells, a process that inevitably damages the healthy cells. But chemotherapy usually is done in a medical setting, according to a hospital's schedule and needs.

A gentler approach

The promise of drug chronotherapy, which uses the same medications but at different times, lies in its individual and precisely timed approach. Ideally the chemo drugs reach the cancerous cells at the most optimal moment for destruction: as they are dividing. And it hits the healthy cells when they are resting, which causes less damage.

"It allows for larger doses to be delivered more frequently, with higher efficacy and lower toxicity," said pioneering chronobiologist William Hrushesky, a senior clinical investigator at the Dorn VA Medical Center in South Carolina. Chronotherapy began in Hrushesky's lab, which originally was at the University of Minnesota.

"It's kinder, gentler and, at the same time, more aggressive and effective," Hrushesky said.

In addition, because patients aren't necessarily receiving treatment at a hospital and saddled with cumbersome equipment, chronotherapy allows for some semblance of a normal life during treatment, an emotional boost that helps healing.

Equipped with a sporty fanny pack and a programmable, portable pump, chrono patients can be hooked up to a catheter in the morning and receive their treatments later in the day or during sleep.

"The infusion starts slowly and ratchets up, hour by hour," said Dr. Keith Block, who has been using chronotherapy at the Block Center for Integrative Cancer Care in Evanston, Ill., since 1998. "It slowly increases to the middle point of the cycle, peaks, infuses most of the drug here, and then slowly ratchets back down, to no drug, where the chrono cycle is completed."

Fazio, who was treated at the Block Center, often went for walks during chemo treatment. Other Block patients have gone in-line skating along Lake Michigan, practiced yoga or received massages as part of the center's holistic treatment plan.

"I was very troubled by the adverse side effects and difficulty patients experience when receiving chemo," said Block, who also directs the integrative-medicine program at the College of Medicine at the University of Illinois at Chicago.

The unpredictable body

The general practice of chronotherapy is controversial in part because most doctors are schooled on the principle of homeostasis, the belief that the body adapts to maintain balance. When we're hungry, we eat. When we're hot, we sweat. Medications are taken once or twice daily (and often timed with meals to ensure compliance), because it's thought that a steady level of an active drug is the best way to tackle a disease.

But "the body is anything but constant," argued Michael Smolensky, co-author of "The Body Clock Guide to Better Health" (Henry Holt, $17) and the director of the Memorial-Hermann Chronobiology Center at the University of Texas at Houston. "It may handle the same dose of the same medication in different ways at different times of the day."

Yet chronotherapy faces both philosophical, logistical and technical hurdles. In addition to Dorn in South Carolina, chronotherapy is offered only at the Block Center and at the Cancer Treatment Centers of America location in Zion.

"It's fundamentally novel, difficult to set up and not something you can bill extra for," said Hrushesky, who has been studying the body clock since 1976.

Chronobiologists have to consider the timing of both the drugs and the cancer cells. Each drug has an ideal time when it should be given. Some research has shown that 5-fluorouracil, a drug used for cancers of the colon, breast and rectum, is best tolerated in the middle of a sleep cycle. So against colon cancer, the drug would be administered between 10 p.m. and 10 a.m., when the healthy cells are at rest and the cancer cells are most active.

Another cancer drug, oxaliplatin, has been shown to be more effective during the day.

But "for the bulk of patients, you don't know exactly what the rhythm is and how normal it is," said Dr. Gini Fleming, director of medical oncology, breast and gynecology at the University of Chicago.

"The sicker someone is, the less likely they will have a normal rhythm. And you don't know which rhythm determines a person's susceptibility to a drug effect. There could be multiple reasons why a drug works better at certain times of day," she said.

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