Can Fasting Blunt Chemotherapy's Debilitating Side Effects?

[Guest guest]

Asking a cancer patient to fast while undergoing chemotherapy may seem

like adding insult to injury. But a dramatic experiment in mice has

led some researchers to suggest that fasting may blunt the side

effects of cancer treatment and perhaps even allow patients to

tolerate higher drug doses. The idea is considered radical, even

worrying, to some oncologists--especially because patients have

already begun trying it on their own. Now, a clinical trial, in which

patients undergoing chemotherapy for bladder and lung cancer will fast

for as long as 3 days with only water to drink, is slated to begin in

the next 2 months.

The strategy is the brainchild of Valter Longo, a gerontology

researcher at the University of Southern California (USC) in Los

Angeles who has long studied how calorie restriction extends life span

in various species. Although the precise mechanism isn't clear, it's

widely believed that cutting calories slows the growth rate of cells

and makes them more stress-resistant, protecting them from the

cumulative damage of aging.

Longo wondered whether this effect might help protect healthy cells

from chemotherapy, which kills rapidly dividing cells, whether normal

or cancerous. In yeast, he found, most cells, as expected, became more

stress-resistant when nutrients were dialed down. But yeast cells

expressing genes similar to the oncogenes that help drive cancer did

not react to calorie restriction; they kept on growing and dividing.

Longo reasoned that in cancer cells " it's the oncogenes that regulate

the stress resistance, " and " those are always on, " causing the cells

to produce growth factors unaffected by calorie restriction.

Longo, along with cancer biologist Lizzia Raffaghello of the Gaslini

Children's Hospital in Genoa, Italy, USC graduate student Changhan

Lee, and their colleagues, tested this strategy in mice. Recognizing

that cancer patients could not endure long-term calorie restriction,

they tried a briefer but more extreme version: total fasting. Mice

starved for 48 to 60 hours and then given high doses of a chemotherapy

drug showed no visible signs of toxicity, yet many control animals

died from the treatment. When the animals were injected with a

neuroblastoma cell line, which mimics an aggressive pediatric cancer,

the fasting combined with chemotherapy didn't appear to blunt the

treatment's effects on the cancer, suggesting that healthy cells were

protected from chemotherapy by fasting but cancer cells were not.

To de Cabo, a researcher who studies aging at the National

Institute on Aging branch in Baltimore, land, the findings make

sense. It's a hallmark of calorie restriction that animals " are much

more resistant to any type of toxin, " he says.

Longo's only publication so far on the subject appeared in late March

in the Proceedings of the National Academy of Sciences, but " a lot of

people are already doing it " on their own, he says. " Even though we

were very clear, 'Don't try this at home,' I get an e-mail every day "

from individuals interested in doing so.

One enthusiast is Cravy, a 66-year-old retired ophthalmologist

in Santa , California, who is battling metastatic prostate

cancer. Cravy just finished his third round of chemotherapy in 2

months, each combined with fasting. After the first round left him

suffering some side effects, Cravy extended the time he fasts after

treatment from about 8 hours to 24 hours, to go beyond the half-life

of the most toxic drug; he also fasts for about 64 hours before

treatment. Cravy now reports virtually no ill effects from

chemotherapy. " On day five [after treatment] was the first time I

played golf and walked the whole golf course, " he says. He admits that

his mental sharpness fades during the 3½ days he fasts. But the

approach has made him much more willing to try chemotherapy, which he

had long resisted because he so feared its side effects.

The possibility that patients will try fasting before the approach has

been properly tested " is exactly my fear, " says Leonard Saltz, an

oncologist who specializes in colon cancer at Memorial Sloan-Kettering

Cancer Center in New York City. " I still do fast on Yom Kippur, " he

says, and those 24 hours without sustenance are a challenge. " Would I

be enthusiastic about enrolling my patients in a trial where they're

asked not to eat for 2½ days? No. "

That, however, is exactly what Longo and clinical colleagues at USC

are gearing up to do. Quinn, a genitourinary oncologist at USC,

is preparing with Longo and others to recruit 12 to 18 bladder and

lung cancer patients who will fast for 24, 48, or 72 hours before and

just after chemotherapy. They will begin gradually, with 24 hours of

fasting, before ramping up. If the fasting appears safe and

potentially effective, the group will recruit another 42 patients, 14

of whom will not fast. Everyone will receive the same chemotherapy

regimen. The work is funded by USC and the V Foundation for Cancer

Research, an advocacy group that funds many mainstream cancer studies.

Quinn hopes fasting will not only minimize chemotherapy's toxicity but

also make cancer cells more susceptible to chemotherapy. Hints of such

increased effectiveness appeared in the mouse data, but the clinical

trial will be too small to test this hypothesis.

" It's reasonable enough to at least look at it in a small number of

patients, " says Alan Sandler, an oncologist who treats lung cancer at

Vanderbilt University in Nashville, Tennessee. " But it really goes

against a lot of the thoughts that people have, that you need to eat

to feel better. "

The possibility that patients will try fasting before the approach has

been properly tested " is exactly my fear, " says Leonard Saltz, an

oncologist who specializes in colon cancer at Memorial Sloan-Kettering

Cancer Center in New York City. " I still do fast on Yom Kippur, " he

says, and those 24 hours without sustenance are a challenge. " Would I

be enthusiastic about enrolling my patients in a trial where they're

asked not to eat for 2½ days? No. "

That, however, is exactly what Longo and clinical colleagues at USC

are gearing up to do. Quinn, a genitourinary oncologist at USC,

is preparing with Longo and others to recruit 12 to 18 bladder and

lung cancer patients who will fast for 24, 48, or 72 hours before and

just after chemotherapy. They will begin gradually, with 24 hours of

fasting, before ramping up. If the fasting appears safe and

potentially effective, the group will recruit another 42 patients, 14

of whom will not fast. Everyone will receive the same chemotherapy

regimen. The work is funded by USC and the V Foundation for Cancer

Research, an advocacy group that funds many mainstream cancer studies.

Quinn hopes fasting will not only minimize chemotherapy's toxicity but

also make cancer cells more susceptible to chemotherapy. Hints of such

increased effectiveness appeared in the mouse data, but the clinical

trial will be too small to test this hypothesis.

" It's reasonable enough to at least look at it in a small number of

patients, " says Alan Sandler, an oncologist who treats lung cancer at

Vanderbilt University in Nashville, Tennessee. " But it really goes

against a lot of the thoughts that people have, that you need to eat

to feel better. "

The possibility that patients will try fasting before the approach has

been properly tested " is exactly my fear, " says Leonard Saltz, an

oncologist who specializes in colon cancer at Memorial Sloan-Kettering

Cancer Center in New York City. " I still do fast on Yom Kippur, " he

says, and those 24 hours without sustenance are a challenge. " Would I

be enthusiastic about enrolling my patients in a trial where they're

asked not to eat for 2½ days? No. "

That, however, is exactly what Longo and clinical colleagues at USC

are gearing up to do. Quinn, a genitourinary oncologist at USC,

is preparing with Longo and others to recruit 12 to 18 bladder and

lung cancer patients who will fast for 24, 48, or 72 hours before and

just after chemotherapy. They will begin gradually, with 24 hours of

fasting, before ramping up. If the fasting appears safe and

potentially effective, the group will recruit another 42 patients, 14

of whom will not fast. Everyone will receive the same chemotherapy

regimen. The work is funded by USC and the V Foundation for Cancer

Research, an advocacy group that funds many mainstream cancer studies.

Quinn hopes fasting will not only minimize chemotherapy's toxicity but

also make cancer cells more susceptible to chemotherapy. Hints of such

increased effectiveness appeared in the mouse data, but the clinical

trial will be too small to test this hypothesis.

" It's reasonable enough to at least look at it in a small number of

patients, " says Alan Sandler, an oncologist who treats lung cancer at

Vanderbilt University in Nashville, Tennessee. " But it really goes

against a lot of the thoughts that people have, that you need to eat

to feel better. "

The possibility that patients will try fasting before the approach has

been properly tested " is exactly my fear, " says Leonard Saltz, an

oncologist who specializes in colon cancer at Memorial Sloan-Kettering

Cancer Center in New York City. " I still do fast on Yom Kippur, " he

says, and those 24 hours without sustenance are a challenge. " Would I

be enthusiastic about enrolling my patients in a trial where they're

asked not to eat for 2½ days? No. "

That, however, is exactly what Longo and clinical colleagues at USC

are gearing up to do. Quinn, a genitourinary oncologist at USC,

is preparing with Longo and others to recruit 12 to 18 bladder and

lung cancer patients who will fast for 24, 48, or 72 hours before and

just after chemotherapy. They will begin gradually, with 24 hours of

fasting, before ramping up. If the fasting appears safe and

potentially effective, the group will recruit another 42 patients, 14

of whom will not fast. Everyone will receive the same chemotherapy

regimen. The work is funded by USC and the V Foundation for Cancer

Research, an advocacy group that funds many mainstream cancer studies.

Quinn hopes fasting will not only minimize chemotherapy's toxicity but

also make cancer cells more susceptible to chemotherapy. Hints of such

increased effectiveness appeared in the mouse data, but the clinical

trial will be too small to test this hypothesis.

" It's reasonable enough to at least look at it in a small number of

patients, " says Alan Sandler, an oncologist who treats lung cancer at

Vanderbilt University in Nashville, Tennessee. " But it really goes

against a lot of the thoughts that people have, that you need to eat

to feel better. "

Couzin

Science 29 August 2008:

Vol. 321. no. 5893, pp. 1146 - 1147

DOI: 10.1126/science.321.5893.1146a

http://snipurl.com/3ks2p [www_sciencemag_org]