title: Dasatinib in previously treated metastatic colorectal cancer: a phase II trial of the University of Chicago Phase II Consortium.
abstract: BACKGROUND
  Treatment options for metastatic colorectal cancer (CRC) are limited after a fluoropyrimidine, oxaliplatin and irinotecan; novel agents need to be explored in this setting. Dasatinib, an oral inhibitor of Src family kinases, inhibits proliferation in CRC cell lines and has antitumor activity in CRC xenograft models.
  
  
  METHODS
  We conducted a multi-center phase II trial of dasatinib in unresectable, previously-treated metastatic CRC patients. No more than 2 prior chemotherapy regimens were permitted, which must have contained a fluoropyrimidine, oxaliplatin and irinotecan. The primary endpoint was progression-free survival (PFS) at 4 months. The Simon two-stage design required that at least 5 of the first 19 patients be progression-free at 4 months to expand to a second stage.
  
  
  RESULTS
  Nineteen patients enrolled at 9 centers. The study was terminated after the first stage due to lack of efficacy. There were no objective responses; 1 patient (5%) had stable disease for 7.3 months. The PFS rate at 4 months was 5.3% (90% CI: 0.3, 22.6). Median PFS was 1.6 months (90% CI: 1.4, 1.8). Median overall survival was 5.1 months (90% CI: 2.4, 6.3). Grade 3/4 toxicities included fatigue in 16% of patients, and anemia, anorexia, nausea/vomiting and dyspnea in 11%.
  
  
  CONCLUSIONS
  Dasatinib is inactive as a single agent in previously treated metastatic CRC patients.
authors.affiliation: Section of Hematology/Oncology, University of Chicago, 5841 S. Maryland Avenue, MC 2115, Chicago, IL 60637-1470, USA.
authors.forename: Manish R
authors.initials: MR
authors.lastname: Sharma
authors.forename: Kristen
authors.initials: K
authors.lastname: Wroblewski
authors.forename: Blase N
authors.initials: BN
authors.lastname: Polite
authors.forename: James A
authors.initials: JA
authors.lastname: Knost
authors.forename: James A
authors.initials: JA
authors.lastname: Wallace
authors.forename: Sanjiv
authors.initials: S
authors.lastname: Modi
authors.forename: Bethany G
authors.initials: BG
authors.lastname: Sleckman
authors.forename: David
authors.initials: D
authors.lastname: Taber
authors.forename: Everett E
authors.initials: EE
authors.lastname: Vokes
authors.forename: Walter M
authors.initials: WM
authors.lastname: Stadler
authors.forename: Hedy L
authors.initials: HL
authors.lastname: Kindler
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000069439:Dasatinib; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D013844:Thiazoles / Q000009:adverse effects / Q000627:therapeutic use*; D019061:src-Family Kinases / Q000037:antagonists & inhibitors
chemical_list: D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D019061:src-Family Kinases; D000069439:Dasatinib