Phase II study of rubitecan, an oral camptothecin in patients with advanced colorectal cancer who have failed previous 5-fluorouracil based chemotherapy

Background: Rubitecan (RFS-2000, 9NC, Orathecin™) is an orally bioavailable camptothecin analogue, with evidence of preclinical activity in colon cancer cell lines. We evaluated oral rubitecan (5 days on, 2 days rest per week) on a continuous schedule, in patients with advanced colorectal cancer (CRC), who progressed after 5-flurouracil based chemotherapy. Patients and results: Fourteen eligible patients were treated with rubitecan at 1.5 mg/m ²/day on a 5 day/week continuous schedule. Therapy was well tolerated with most adverse events in the mild to moderate category. Grade 3/4 toxicity consisting of anemia, diarrhea and elevated bilirubin was seen in 4 patients. No responses were seen in 13 evaluable patients. Overall median survival (95% confidence interval) was 10.1 (range 3.1-12.6) months, and median time to progression was 2.1 months. Conclusions: Administration of rubitecan was well tolerated, but this schedule does not appear to have clinical activity in patients with advanced previously treated CRC.