title: Phase 2 study of dasatinib in the treatment of head and neck squamous cell carcinoma.
abstract: BACKGROUND
  Treatment options for patients with advanced head and neck squamous cell carcinoma (HNSCC) are scarce. This phase 2 study was conducted to evaluate the safety, tolerability, pharmacokinetics, and efficacy of dasatinib in this setting.
  
  
  METHODS
  Patients with recurrent and/or metastatic HNSCC after platinum-based therapy were treated with dasatinib either orally or via percutaneous feeding gastrostomy (PFG). Primary endpoints were 12-week progression-free survival (PFS) and objective response rate with a 2-stage design and early withdrawal if the 12-week PFS rate was ≤20% and no patients had an objective response (OR). Forty-nine serum cytokines and angiogenic factors (CAFs) were analyzed from treated patients.
  
  
  RESULTS
  Of the 15 patients enrolled, 12 were evaluable for response, and all patients were evaluable for toxicity. No OR was observed and 2 patients (16.7%) had stable disease (SD) at 8 weeks. The median treatment duration was 59 days, the median time to disease progression was 3.9 weeks, and the median survival was 26 weeks. One patient required a dose reduction, 3 patients required dose interruptions, and 4 patients were hospitalized for toxicity. Dasatinib inhibited c-Src both when administered orally and via PFG. Greater mean drug exposure, decreased half-life, and greater maximum concentration were observed in patients receiving dasatinib via PFG. Eleven baseline CAFs were associated with treatment outcome and 1 CAF, macrophage migration inhibitory factor, was found to be differentially modulated in correlation with SD versus disease progression.
  
  
  CONCLUSIONS
  Single-agent dasatinib failed to demonstrate significant activity in patients with advanced HNSCC, despite c-Src inhibition. The toxicity profile was consistent with that reported in other solid tumors, and the drug can be given via PFG tube.
authors.affiliation: Division of Cancer Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Heather D
authors.initials: HD
authors.lastname: Brooks
authors.forename: Bonnie S
authors.initials: BS
authors.lastname: Glisson
authors.forename: B Nebiyou
authors.initials: BN
authors.lastname: Bekele
authors.forename: Faye M
authors.initials: FM
authors.lastname: Johnson
authors.forename: Lawrence E
authors.initials: LE
authors.lastname: Ginsberg
authors.forename: Adel
authors.initials: A
authors.lastname: El-Naggar
authors.forename: Kirk S
authors.initials: KS
authors.lastname: Culotta
authors.forename: Naoko
authors.initials: N
authors.lastname: Takebe
authors.forename: John
authors.initials: J
authors.lastname: Wright
authors.forename: Hai T
authors.initials: HT
authors.lastname: Tran
authors.forename: Vassiliki A
authors.initials: VA
authors.lastname: Papadimitrakopoulou
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D002648:Child; D016207:Cytokines / Q000032:analysis; D000069439:Dasatinib; D018572:Disease-Free Survival; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013844:Thiazoles / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D016207:Cytokines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D000069439:Dasatinib