Study Evaluates Ability of Drug to Overcome Resistance to Standard Colorectal Cancer Therapy

BUFFALO, NY- Roswell Park scientists are investigating a new combination of drugs for colorectal cancer patients who have become intolerant or resistant to standard therapies. Marwan Fakih, MD, Department of Medicine at Roswell Park Cancer Institute will present the results of a phase I clinical study at the American Society of Clinical Oncology (ASCO) 2009 annual meeting, May 29 – June 2, in Orlando, FL.

“A Phase I Clinical Trial of Vorinostat in Combination with sFULV2 in Patients with Refractory Solid Tumors”
Sunday, May 31 – 8 am EST Level 2, West Hall C

Aggressive colorectal cancers can develop resistance to standard therapy of 5- fluorouracil (5-FU) and leucovorin, and progress. Vorinostat is a chemotherapy drug that modifies the structure of chromatin (DNA-protein complex) and therefore modifies the expression of various important genes that are implied in cancer growth. Vorinostat is of specific interest due to its ability to regulate the expression of the thymidylate synthase protein, which is associated with 5-FU resistance. Several laboratory studies have previously shown that the combination of vorinostat and 5-FU have greater anti-tumor activity than 5-FU alone.

Dr. Fakih, the lead investigator on this study, and colleagues evaluated the effectiveness of 5-FU and vorinostat in 27 patients with solid tumors who had failed standard therapies. The investigators were able to escalate vorinostat safely up to 1700mg/day, three times a week, in combination with biweekly administration of 5-FU. Of the 24 colorectal cancer patients who were drug-resistant, one had a partial response lasting more than one year, and 12 patients had stable disease. The median time to disease progression was 4.4 months and the overall survival was 9.2 months.

"These results are very encouraging, given that the overall survival of untreated advanced chemotherapy-resistant colorectal cancer is 4.5 months,” said Dr. Fakih. “The fact that we have established tumor shrinkage with vorinostat with this group of patients suggests that vorinostat may overcome 5-FU resistance.” Dr. Fakih and colleagues are currently conducting a phase II study of vorinostat plus 5-fluorouracil in patients with refractory colorectal cancer.

Colorectal cancer is the third most commonly diagnosed cancer in the United States. An estimated 108,070 new cases of colon cancer will be diagnosed this year and 49,960 patients will die from the disease.

The mission of Roswell Park Cancer Institute (RPCI) is to understand, prevent and cure cancer. RPCI, founded in 1898, was one of the first cancer centers in the country to be named a National Cancer Institute-designated comprehensive cancer center and remains the only facility with this designation in Upstate New York. The Institute is a member of the prestigious National Comprehensive Cancer Network, an alliance of the nation’s leading cancer centers; maintains affiliate sites; and is a partner in national and international collaborative programs. For more information, visit RPCI’s website at http://www.roswellpark.org, call 1-877-ASK-RPCI (1-877-275-7724) or email askrpci@roswellpark.org.

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Source:
1. Study Evaluates Ability of Drug to Overcome Resistance to Standard Colorectal Cancer Therapy