BUFFALO, NY – Marwan G. Fakih, MD, Staff Physician, Department of Medicine, at Roswell Park Cancer Institute, will present the results of a phase I study to evaluate the safety and determine the maximum tolerated dose of vorinostat in combination with 5- fluorouracil (5-FU), plus oxaliplatin, plus leucovorin (FOLFOX) in patients with advanced colorectal cancer at the 2007 annual meeting of the American Society of Clinical Oncology (ASCO), June 1- 5 in Chicago, IL.

 “A phase I study of vorinostat (suberoylanilide hydroxamic acid) in combination with 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) in patients with advanced colorectal cancer (CRC).

Embargoed until Monday, June 4, 8 am CST

S Hall A2

Poster Number: H1     Abstract No: 4088

Vorinostat is a histone deacetylase inhibitor that has been shown to decrease the expression of thymidylate synthase (TS) in preclinical trials. Given the association of TS overexpression with 5-FU resistance and the synergistic antitumor activity noted when vorinostat is added to 5-FU, Dr. Fakih and his colleagues conducted a phase I study of 19 patients with advanced colorectal cancer, all of whom had failed prior treatment with FOLFOX.

Vorinostat was given twice daily for seven days every 14 days, while FOLFOX was administered over two days (on the fourth day of vorinosotat). Vorinostat was tolerated in combination with FOLFOX up to a dose of 300mg orally twice daily, which was declared the maximum tolerated dose. The most common side effects included diarrhea, nausea and vomiting, fatigue and bone marrow suppression. Eight patients in the study had stable disease, four of which were confirmed on subsequent repeat CT scans. These findings are encouraging given the refractory patient population.

The study also investigated the pharmacokinetics and pharmacodynamics of vorinostat. The serum concentrations of vorinostat increased with increasing dose levels, but did not reach levels associated with maximum down-regulation of TS in preclinical models. This was consistent with the lack of significant down-regulation of TS on sequential tumor biopsies in patients studied. These results led to the design of an ongoing clinical trial to evaluate a schedule of vorinostat/FOLFOX that is more likely to allow for the administration of higher doses of vorinostat and thus better likelihood of down-regulation TS.

The American Society of Clinical Oncology (ASCO) is a non-profit organization, founded in 1964, with overarching goals of improving cancer care and prevention and ensuring that all patients with cancer receive care of the highest quality. Nearly 25,000 oncology practitioners belong to ASCO, representing all oncology disciplines (medical, radiologic, and surgical oncology) and subspecialties. Members include physicians and health-care professionals participating in approved oncology training programs, oncology nurses, and other practitioners with a predominant interest in oncology. 

Roswell Park Cancer Institute, founded in 1898, is the nation’s first cancer research, treatment and education center and is the only National Cancer Institute-designated comprehensive cancer center in Upstate New York. RPCI is a member of the prestigious National Comprehensive Cancer Network, an alliance of the nation’s leading cancer centers. Roswell Park has affiliate sites and collaborative programs in New York, Pennsylvania, and in China. For more information, visit RPCI’s website at www.roswellpark.org, call 1-877-ASK-RPCI (1-877-275-7724) or e-mail askrpci@roswellpark.org.

-30-