Annals of Oncology 14:1270-1273, 2003
© 2003 European Society for Medical Oncology
Original Paper |
Phase II study of flavopiridol in patients with advanced colorectal cancer
1 Department of Medicine, University of Chicago, Chicago, IL; 2 Sidney Kimmel Cancer Center at Johns Hopkins, Baltimore, MD, USA
Received 28 March 2003; accepted 23 April 2003
Background:
Flavopiridol, a synthetic flavone that inhibits cell cycle progression, has demonstrated activity in colon cancer in xenografts and in a phase I trial. We evaluated flavopiridol in a phase II trial in patients with previously untreated advanced colorectal cancer (ACRC).
Patients and methods:
Twenty chemotherapy-naïve patients with ACRC received flavopiridol at a dose of 50 mg/m2/day via a 72-h continuous infusion every 14 days. Response was assessed by computed tomography or magnetic resonance imaging every 8 weeks.
Results:
Twenty patients were enrolled; 19 were evaluable for toxicity and 18 for response. There were no objective responses. Five patients had stable disease lasting a median of 7 weeks. The median time to progression was 8 weeks. Median survival was 65 weeks. The principal grade 3/4 toxicities were diarrhea, fatigue and hyperglycemia, occurring in 21%, 11% and 11% of patients, respectively. Other common toxicities included anemia, anorexia and nausea/vomiting.
Conclusions:
Flavopiridol in this dose and schedule does not have single-agent activity in patients with ACRC. Recent preclinical data suggest that flavopiridol enhances apoptosis when combined with chemotherapy. Trials that evaluate flavopiridol in combination with active cytotoxic drugs should help to define the role of this novel agent in ACRC.
Key words: clinical trial, colorectal cancer, flavopiridol
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