Phase II study of flavopiridol in patients with advanced colorectal cancer.
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).


METHODS
Twenty chemotherapy-naïve patients with ACRC received flavopiridol at a dose of 50 mg/m(2)/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.
Aklilu
M
M
Department of Medicine, University of Chicago, Chicago, IL, USA.
Kindler
H L
HL
Donehower
R C
RC
Mani
S
S
Vokes
E E
EE
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D016001:Confidence Intervals; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005419:Flavonoids / Q000008:administration & dosage* / Q000009:adverse effects; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D008279:Magnetic Resonance Imaging; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009367:Neoplasm Staging; D010880:Piperidines / Q000008:administration & dosage* / Q000009:adverse effects; D011336:Probability; D016019:Survival Analysis; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D005419:Flavonoids; D010880:Piperidines; C077990:alvocidib