Clinical Benefit of New Targeted Agents in Phase I Trials in Patients with Advanced Colorectal Cancer

Background: Standard treatment for patients with advanced colorectal cancer (ACRC) includes fluoropyrimidines in combination with oxaliplatin or irinotecan. The addition of targeted agents such as bevacizumab and cetuximab to these chemotherapy backbones further improved outcome with survival rates. However, even after intensive treatment, most tumors will subsequently progress and some patients are offered experimental phase I therapies. Patients and Methods: We retrospectively analyzed the outcome for 78 ACRC patients treated consecutively within 23 phase I trials at the Royal Marsden Hospital (RMH) between January 2004 and January 2008. Results: The median age was 62 years (range 26-78). After a median follow-up time of 21.4 weeks (range 1.7-115.6) the median progression-free survival and overall survival (OS) were 8.6 weeks (95% CI: 6.4-10.7) and 29.1 weeks (95% CI: 15.7-42.5), respectively. 28.8 and 8.2% of the patients were assessed as having stable disease (SD) at 3 and 6 months, respectively. Patients with SD had an OS of 40.6 weeks (95% CI: 32.9-48.2) compared to 17.4 weeks (95% CI: 14.0-20.8, p = 0.017) for patients with progressive disease. Conclusion: A limited number of patients with ACRC who failed conventional treatments can derive clinical benefit by participating in phase I cancer trials, and the use of the RMH prognostic score can help to identify these patients. Copyright (C) 2009 S. Karger AG, Basel