title: Treatment-related toxicities in a phase II trial of dasatinib in patients with squamous cell carcinoma of the lung.
abstract: BACKGROUND
  Advanced squamous cell carcinoma (SqCC) of the lung carries a poor prognosis, and new therapeutic targets are needed. Several studies have examined dasatinib in non-small cell lung cancer; these report not only significant toxicities, but also responses in patients found to harbor mutations in discoidin domain receptor tyrosine kinase 2 or BRAF. An open-label phase II trial with dasatinib was carried out to determine the response rates in patients with SqCC who had previously failed standard chemotherapy and to correlate responses with patient genotype.
  
  
  METHODS
  Patients were treated with dasatinib 140 mg daily in 28-day cycles. Patients were included if they had stage IIIb/IV SqCC, Eastern Cooperative Oncology Group performance status of 0 or 1, and for whom treatment with standard chemotherapy had failed.
  
  
  RESULTS
  The study was halted after enrolling five patients, all of whom were discontinued from the trial because of excess toxicity of dasatinib administered at 140 mg/day. The patients were treated for 9, 14, 24, 40, and 42 days. Three of five patients (60%) experienced grade 3 or more toxicities (dyspnea, fatigue, elevated level of aspartate transaminase, anorexia, nausea). Intolerable grade 2 pleural effusions were noted in two of five patients. Four of five patients died after 44, 52, 127, and 226 days; one patient remains alive at 279 days. No deaths were associated with the study drug.
  
  
  CONCLUSIONS
  Similar to other studies, this study too found that dasatinib administered at 140 mg/day for the treatment of advanced SqCC of the lung is associated with excess adverse events, so is not recommended in unselected patients. Further work to identify patients likely to benefit from dasatinib and to manage dasatinib-related toxicities is needed.
authors.affiliation: *Massachusetts General Hospital Cancer Center, Boston, Massachusetts; †Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts; ‡Department of Pathology and Center for Advanced Molecular Diagnostics, Brigham and Women's Hospital, Boston, Massachusetts; and §Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Brunner
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Costa
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Heist
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Garcia
authors.forename: Neal I
authors.initials: NI
authors.lastname: Lindeman
authors.forename: Lynette M
authors.initials: LM
authors.lastname: Sholl
authors.forename: Geoffrey R
authors.initials: GR
authors.lastname: Oxnard
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Johnson
authors.forename: Peter S
authors.initials: PS
authors.lastname: Hammerman
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D000069439:Dasatinib; D064420:Drug-Related Side Effects and Adverse Reactions / Q000175:diagnosis*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D011743:Pyrimidines / Q000009:adverse effects*; D015996:Survival Rate; D013844:Thiazoles / Q000009:adverse effects*; D016896:Treatment Outcome
chemical_list: D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D000069439:Dasatinib