Researchers identify genetic markers to predict response to chemotherapy for
colorectal cancer
06 Jun 2004



One of the most common challenges facing oncologists today is determining the
best course of treatment for their patients--one that would be effective and
have the fewest possible side effects. In a study presented today at the 40th
Annual Meeting of the American Society of Clinical Oncology in New Orleans, Fox
Chase Cancer Center researchers have identified genetic markers in the blood
that can help predict a patient's response to and side effects from irinotecan,
a common chemotherapy drug for colorectal cancer.

Leslie E. Carlini, Ph.D., a research associate in the Fox Chase laboratory of
Rebecca L. Blanchard, Ph.D., presented the findings. Their research focuses on
genetic variations that influence the effect of medicines on different
people--an area of study called pharmacogenetics. Ultimately, the goal is to
improve the way drugs are prescribed by identifying individuals who are likely
to benefit from a specific medicine or who are at increased risk of serious side
effects.

"Our data suggest that variations in genes that help metabolize irinotecan may
be useful predictors of how well colorectal cancer patients respond to this drug
and how severe side effects will be," Carlini said.

To see how genetic variations affected response and side effects, the laboratory
analyzed DNA in blood samples taken during a multi-site clinical trial to test
an investigational combination chemotherapy regimen for metastatic colorectal
cancer. The patients received intravenous irinotecan once a week and twice-daily
tablets of the drug capecitabine for two weeks of a three-week treatment cycle.

The researchers looked at a family of genes called UGTs
(UDP-glucuronosyltransferases), involved in breaking down irinotecan within the
body and ultimately disposing of it. "Our research indicates that patients
specific UGT1A7 or UGT1A9 genotypes will get more anti-tumor response from the
chemotherapy combination. What's more, these patients should have fewer side
effects," Carlini said.

There were no statistically significant associations between the other two UGT
genes and either side effects or antitumor response. "In reality, physicians
will soon be able to personalize cancer therapies based on the tumor's
characteristics and the genetic profile of the person," said Carlini. "The
ultimate goal is to tailor treatment that offers the most anti-tumor activity
with the fewest side effects."

In a separate study based on the same clinical trial, Fox Chase researchers also
discovered a protein marker to help predict response to combination chemotherapy
with capecitabine and irinotecan. Medical oncologist Neal J. Meropol will
present these results at the ASCO annual meeting in a Gastrointestinal
(Colorectal) Cancer Session on Sunday, June 6 between 8 a.m. and 12 noon
(Abstract # 3520, Poster #11).

In addition to Blanchard and Meropol, Carlini's colleagues in the study include
Y.-M. Chen, Ph.D., T. Hill, and C. McGarry of Roche Labs, Nutley, N.J.; and P.
J. Gold, M.D., of the Swedish Cancer Institute, Seattle, Wash.

Fox Chase Cancer Center was founded in 1904 in Philadelphia, Pa., as the
nation's first cancer hospital. In 1974, Fox Chase became one of the first
institutions designated as a National Cancer Institute Comprehensive Cancer
Center. Fox Chase conducts basic, clinical, population and translational
research; programs of prevention, detection and treatment of cancer; and
community outreach. For more information about Fox Chase activities, visit the
Center's web site at www.fccc.edu or call 1-888-FOX CHASE.

Contact: Karen C. Mallet
k_carter@...
215-728-2700
Fox Chase Cancer Center

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