title: Phase II trial of flavopiridol, a cyclin dependent kinase inhibitor, in untreated metastatic malignant melanoma.
abstract: OBJECTIVE
  To test the activity of the cyclin dependent kinase (cdk) inhibitor flavopiridol in malignant melanoma, a disease with frequent abnormalities of the cyclin dependent kinase system.
  
  
  METHODS
  Patients had histologically proven, unidimensionally measurable malignant melanoma, incurable by standard therapy. Prior adjuvant immunotherapy was allowed, but patients were otherwise untreated for advanced disease. Flavopiridol was administered at a dose of 50 mg/m(2) IV over 1 hour daily x 3 days every 3 weeks. Patients were assessed for response every 2 cycles.
  
  
  RESULTS
  17 patients were accrued over 5 months. No objective responses were documented in the 16 patients evaluable for response. Seven patients (44%) had stable disease after 2 cycles, with a median of 2.8 months (range 1.8-9.2). The most common treatment-related non-hematologic toxicities were diarrhea (82%), nausea (47%), fatigue (41%), anorexia (35%) and vomiting (29%). Most treatment-related toxicities were mild, except for diarrhea (grade 3 in 3 patients, grade 4 in 1 patient), nausea (grade 3 in 1 patient) and tumor pain (grade 3 in 1 patient). Hematologic toxicities were minimal, none worse than grade 2. Eighty-eight percent of patients received >/=90% planned dose intensity; 2 patients had dose reductions for gastrointestinal (GI) toxicity.
  
  
  CONCLUSIONS
  Flavopiridol is well tolerated at the dose regimen used in this study, with an acceptable (primarily GI) toxicity profile. Although 7 of the 16 patients had stable disease ranging from 1.8 to 9.2 months in duration, there was no evidence of significant clinical activity in malignant melanoma by objective response criteria.
authors.affiliation: McGill University, Montreal, Quebec, Canada. Susan.Burdette-Radouz@vtmednet.org
authors.forename: Susan
authors.initials: S
authors.lastname: Burdette-Radoux
authors.forename: Richard G
authors.initials: RG
authors.lastname: Tozer
authors.forename: Reinhard C
authors.initials: RC
authors.lastname: Lohmann
authors.forename: Ian
authors.initials: I
authors.lastname: Quirt
authors.forename: D Scott
authors.initials: DS
authors.lastname: Ernst
authors.forename: Wendy
authors.initials: W
authors.lastname: Walsh
authors.forename: Nancy
authors.initials: N
authors.lastname: Wainman
authors.forename: A Dimitrios
authors.initials: AD
authors.lastname: Colevas
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Eisenhauer
mesh_terms: D000328:Adult; D000368:Aged; D000855:Anorexia / Q000139:chemically induced; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D003967:Diarrhea / Q000139:chemically induced; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005419:Flavonoids / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D020714:Maximum Tolerated Dose; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced
chemical_list: D000970:Antineoplastic Agents; D005419:Flavonoids; D010880:Piperidines; C077990:alvocidib; D018844:Cyclin-Dependent Kinases