Phase II study of flavopiridol in patients with advanced colorectal cancer

M. Aklilu, H. L. Kindler, R. C. Donehower, Sridhar Mani, E. E. Vokes

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1270-1273
Number of pages4
JournalAnnals of Oncology
Volume14
Issue number8
DOIs
StatePublished - Aug 1 2003
Externally publishedYes

Fingerprint

alvocidib
Colorectal Neoplasms
flavone
Drug Therapy
Anorexia
Heterografts
Hyperglycemia
Colonic Neoplasms
Nausea
Vomiting
Fatigue
Anemia
Diarrhea
Appointments and Schedules
Cell Cycle

Keywords

  • Clinical trial
  • Colorectal cancer
  • Flavopiridol

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Phase II study of flavopiridol in patients with advanced colorectal cancer. / Aklilu, M.; Kindler, H. L.; Donehower, R. C.; Mani, Sridhar; Vokes, E. E.

In: Annals of Oncology, Vol. 14, No. 8, 01.08.2003, p. 1270-1273.

Research output: Contribution to journalArticle

Aklilu, M, Kindler, HL, Donehower, RC, Mani, S & Vokes, EE 2003, 'Phase II study of flavopiridol in patients with advanced colorectal cancer', Annals of Oncology, vol. 14, no. 8, pp. 1270-1273. https://doi.org/10.1093/annonc/mdg343
Aklilu, M. ; Kindler, H. L. ; Donehower, R. C. ; Mani, Sridhar ; Vokes, E. E. / Phase II study of flavopiridol in patients with advanced colorectal cancer. In: Annals of Oncology. 2003 ; Vol. 14, No. 8. pp. 1270-1273.
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abstract = "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-na{\"i}ve 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.",
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