title: A phase II study of flavopiridol in patients with advanced renal cell carcinoma: results of Southwest Oncology Group Trial 0109.
abstract: OBJECTIVE
  Flavopiridol is a cyclin-dependent kinase inhibitor that prevents cell cycle progression and tumor growth. In initial phase I studies, encouraging responses were seen in advanced renal cell cancer (RCC). In a phase II study of flavopiridol given as a 72-h continuous infusion every 2 weeks in RCC, a response rate of 6% was seen but with considerable grade 3 or 4 asthenia, diarrhea, and thrombosis. Subsequently, an alternative 1-h bolus schedule was reported to have enhanced tolerability in a phase I trial. We therefore conducted a phase II study of this bolus regimen.
  
  
  METHODS
  A total of 38 patients with advanced RCC were entered into this multi-institutional phase II study. Flavopiridol (50 mg/m(2) per day) was administered by bolus intravenous injection daily for three consecutive days, repeated every 3 weeks.
  
  
  RESULTS
  Out of 34 eligible patients, one complete response and three partial responses were observed, for an overall response rate of 12% (95% CI 3-27%). Of the 34 patients, 14 (41%) had stable disease (SD). The probability of not failing treatment by 6 months was 21% (95% CI 9-35%). Median overall survival time was 9 months (95% CI 8-18 months). The most common grade 3 or 4 toxicities were diarrhea (35%) and tumor pain (12%) along with anemia, dyspnea, and fatigue (9% each).
  
  
  CONCLUSIONS
  Flavopiridol at this dose and schedule is feasible with an acceptable toxicity profile. Flavopiridol has some modest biologic activity against advanced RCC, as evidenced by its single-agent objective response and SD rates.
authors.affiliation: University of Kansas Medical Center, Kansas City, KS, USA. peter.vanveldhuizen@med.va.gov
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Van Veldhuizen
authors.forename: James R
authors.initials: JR
authors.lastname: Faulkner
authors.forename: Primo N
authors.initials: PN
authors.lastname: Lara
authors.forename: Paul H
authors.initials: PH
authors.lastname: Gumerlock
authors.forename: J Wendall
authors.initials: JW
authors.lastname: Goodwin
authors.forename: Shaker R
authors.initials: SR
authors.lastname: Dakhil
authors.forename: Howard M
authors.initials: HM
authors.lastname: Gross
authors.forename: Robert C
authors.initials: RC
authors.lastname: Flanigan
authors.forename: E David
authors.initials: ED
authors.lastname: Crawford
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D003967:Diarrhea / Q000139:chemically induced; D004334:Drug Administration Schedule; D005260:Female; D005419:Flavonoids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007275:Injections, Intravenous; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000139:chemically induced; D010880:Piperidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D005419:Flavonoids; D010880:Piperidines; C077990:alvocidib