Addition of Irinotecan to Standard Chemotherapy Improves Survival in a Subset of Stage III Colon Cancer Patients


Key Points

  • The addition of irinotecan to standard fluorouracil/leucovorin resulted in a trend toward improved overall survival in patients with CpG island methylator phenotype (CIMP)-positive colon cancer.
  • Results were most pronounced among patients with stage III CIMP-positive, mismatch repair–intact colon cancer.
  • In patients with CIMP-negative disease, the addition of irinotecan resulted in decreased overall survival compared to standard chemotherapy alone.

A subset of patients with stage III colon cancer had improved survival rates when treated with irinotecan-based therapy, according to a new study in Gastroenterology. When added to the standard chemotherapy treatment—fluorouracil [5-FU] and leucovorin—adjuvant irinotecan therapy improved overall survival rates for 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, exhibited 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 study author Stacey Shiovitz, MD, from the Department of Medicine, University of Washington, Seattle, and the clinical research division of Fred Hutchinson Cancer Research Center, Seattle. “Based on our findings, identification of a tumor’s CIMP status should play a greater role in the clinical setting.”

Study Details

Researchers analyzed data from patients with stage III colon cancer randomly assigned to groups given 5-FU/leucovorin or adjuvant irinotecan after surgery, from April 1999 through April 2001. Patients were followed for 8 years. Patients with CIMP-positive tumors demonstrated a trend toward improved overall survival when treated with irinotecan vs the standard treatment alone, 69% vs 56%, respectively. 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 KRAS/BRAF mutation status.

“This analysis serves to increase our understanding of which subset of patients might benefit from irinotecan adjuvant therapy. 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,” added Dr. Shiovitz.

Future studies are needed to better understand the origin of the CIMP phenotype and to test these findings in a larger subset.

William M. Grady, MD, of the University of Washington and Fred Hutchinson Cancer Research Center, is the corresponding author for the Gastroenterology article.

This study was supported by funding from the Lattner Family Foundation, RACE Charities, Burroughs Wellcome Fund and National Institutes of Health. The study authors reported no potential conflicts of interest.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.