Sarcoma 
Volume 2006 (2006), Article ID 64374, 7 pages
doi:10.1155/SRCM/2006/64374
Clinical Study

A Phase II Study of Flavopiridol in Patients With Previously Untreated Advanced Soft Tissue Sarcoma

Don G. Morris,1 Vivien H. C. Bramwell,1 Robert Turcotte,2 Alvaro T. Figueredo,3 Martin E. Blackstein,4 Shail Verma,5 Sarah Matthews,6 and Elizabeth A. Eisenhauer6

 1Department of Medicine, Tom Baker Cancer Centre, University of Calgary, Alberta T2N 4N2, Canada
2Department of Orthopaedic Surgery, McGill University Health Centre, Montreal H3G 1A4, Quebec, Canada
3Department of Medical Oncology, Juravinski Cancer Centre, Hamilton Health Scineces, Hamilton L8V 5C2, Ontario, Canada
4Department of Anat. (Histol) & Med, Mount Sinai Hospital, University of Toronto, Toronto M5G 1X5, Ontario, Canada
5Department of Medicine, University of Ottawa, Ottawa K1H 1C4, Ontario, Canada
6NCIC Clinical Trials Group, Queen's University, Kingston K7L 3N6, Ontario, Canada
Received 16 November 2005; Revised 5 July 2006; Accepted 25 July 2006

Abstract

Purpose. Flavopiridol is a potent cyclin-dependent kinase (CDK) inhibitor that has preclinical activity in many tumours. This synthetic flavonoid was tested in a phase II nonrandomized, nonblinded multicentre clinical trial to determine its activity and toxicity in patients with previously untreated metastatic or locally advanced soft tissue sarcoma. Methods. A total of 18 patients with histologically confirmed nonoperable soft tissue was treated with flavopiridol administered at a dose of 50 mg/m2 IV over 1 hour daily ×3 days every 3 weeks. Results. Eighteen patients were accrued to the study over a period of 6 months. No objective responses were noted in the seventeen evaluable patients. Eight patients (47%) exhibited stable disease after 2 cycles (median duration of 4.3 months (range 1.4–6.9 months). Kaplan-Meier estimates for 3- and 6-month progression-free survivial rates were 44 percent and 22 percent, respectively. The only grade 3 toxicities were diarrhea (N=2), nausea (N=2), gastritis (N=1), and fatigue (N=1). Ninety-four percent of patients received ≥ 90% of the planned dose intensity, during 55 treatment cycles. Conclusions. Flavopiridol was well tolerated at the dose and schedule used in this study, however, no objective treatment responses were seen and thus our results do not support further exploration of flavopiridol as a monotherapy at this dose and schedule in soft tissue sarcomas.