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Irinotecan-Based Therapy Shows Promise in Subset of Stage III Colon Cancer Patients

CIMP status plays crucial role

A subset of patients with stage III colon cancer showed improved survival rates when treated with irinotecan-based therapy, according to a new study in Gastroenterology, the journal of the American Gastroenterological Association.

When added to the standard chemotherapy treatment — fluorouracil and leucovorin — adjuvant irinotecan therapy improved overall survival rates in patients with the CpG island methylator phenotype (CIMP). CIMP is seen in about 10% to 20% of colorectal cancers. Patients with CIMP-negative tumors, however, experienced significant harm from the addition of irinotecan — overall survival was 68% compared with 78% for those receiving the standard treatment alone.

“Our results serve as an example that the molecular characterization of individual tumors may help to determine the most appropriate treatment for patients with colon cancer,” said lead author Stacey Shiovitz, MD, of the University of Washington. “Based on our findings, identification of a tumor’s CIMP status should play a greater role in the clinical setting.”

Researchers analyzed data from patients with stage III colon cancer who were randomly assigned to receive fluorouracil and leucovorin or adjuvant irinotecan after surgery from April 1999 through April 2001. The patients were followed for 8 years.

Patients with CIMP-positive tumors demonstrated a trend toward improved overall survival when treated with irinotecan compared with standard treatment alone (69% vs. 56%, respectively). The results were most pronounced among patients with stage III, CIMP-positive, mismatch repair intact (MMR-I) colon cancer.

No significant associations or interactions between CIMP and KRAS or BRAF mutations were observed, suggesting that the effectiveness of this treatment is not influenced by the patient’s KRAS/BRAF mutation status.

“This analysis serves to increase our understanding of which subset of patients might benefit from irinotecan adjuvant therapy,” Shiovitz said. “This research is an important step in the medical community’s work to classify tumors into groups that would result in optimized treatment strategies, thus delivering a higher level of personalized care to patients.”

Future studies are needed to better understand the origin of the CIMP phenotype, she added.

Source: AGA; August 28, 2014.

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