Original Paper

A Phase II Study of Flavopiridol (Alvocidib) in Combination with Docetaxel in Refractory, Metastatic Pancreatic Cancer
Richard D. Carvajal^a, Archie Tse^a, Manish A. Shah^a, Robert A. Lefkowitz^b, Mithat Gonen^c, Lisa Gilman-Rosen^a, Jeremy Kortmansky^d, David P. Kelsen^a, Gary K. Schwartz^a, Eileen M. O'Reilly^a

Departments of
^aMedicine,
^bRadiology and
^cBiostatistics and Epidemiology, Memorial Sloan-Kettering Cancer Center, New York, N.Y., and
^dDepartment of Medical Oncology and Hematology, New Haven, Conn., USA

Address of Corresponding Author

Pancreatology 2009;9:404-409 (DOI: 10.1159/000187135)

  Key Words

• Cyclin-dependent kinase inhibitors
• Docetaxel
• Flavopiridol
• Gemcitabine-refractory cancer
• Pancreatic adenocarcinoma

  Abstract

Background/Aims: Pancreatic adenocarcinoma (PC) harbors frequent alterations in p16, resulting in cell cycle dysregulation. A phase I study of docetaxel and flavopiridol, a pan-cyclin-dependent kinase inhibitor, demonstrated encouraging clinical activity in PC. This phase II study was designed to further define the efficacy and toxicity of this regimen in patients with previously treated PC. Methods: Patients with gemcitabine-refractory, metastatic PC were treated with docetaxel 35 mg/m² followed by flavopiridol 80 mg/m² on days 1, 8, and 15 of a 28-day cycle. Tumor measurements were performed every two cycles. A Simon two-stage design was used to evaluate the primary endpoint of response. Results: Ten patients were enrolled, and 9 were evaluable for response. No objective responses were observed; however, 3 patients (33%) achieved transient stable disease, with one of these patients achieving a 20% reduction in tumor size. Median survival was 4.2 months, with no patients alive at the time of analysis. Adverse events were significant, with 7 patients (78%) requiring 1 dose reduction for transaminitis (11%), grade 4 neutropenia (33%), grade 3 fatigue (44%), and grade 3 diarrhea (22%). Conclusions: The combination of flavopiridol and docetaxel has minimal activity and significant toxicity in this patient population. These results reflect the challenges of treating patients with PC in a second-line setting where the risk/benefit equation is tightly balanced.

Copyright © 2009 S. Karger AG, Basel and IAP

  Author Contacts

Richard D. Carvajal, MD
Melanoma/Sarcoma Service, Department of Medicine
Memorial Sloan-Kettering Cancer Center
1275 York Avenue, New York, NY 10021 (USA)
Tel. +1 212 639 5096, Fax +1 212 717 3320, E-Mail carvajar@mskcc.org

  Article Information

Received: July 7, 2008
Accepted after revision: December 4, 2008
Published online: May 19, 2009
Number of Print Pages : 6
Number of Figures : 1, Number of Tables : 2, Number of References : 31