Neoadjuvant dasatinib for muscle-invasive bladder cancer with tissue analysis of biologic activity

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Objectives: Preclinical urothelial carcinoma models suggest activity of dasatinib, an oral SRC-family kinase (SFK) inhibitor. We sought to determine the feasibility and biologic activity of neoadjuvant dasatinib (Neo-D) in patients with muscle-invasive urothelial carcinoma of the bladder (miUCB) preceding radical cystectomy (RC). Materials and methods: A prospective multisite phase II trial was conducted. Key eligibility criteria included: resectable miUCB (T2-T4a, N0, M0), and Eastern Cooperative Oncology Group performance status 0 to 1. Patients received oral Neo-D 100. mg once daily for 28±7 days followed by RC 8 to 24 hours after the last dose. The primary end point was feasibility, defined as≥60% of patients with miUCB completing therapy without treatment-related dose-limiting toxicity (DLT). Pre- and posttreatment tumor immunohistochemistry of phosphorylated SFK (pSFK), Ki-67, and cleaved caspase (Cas)-3 results were analyzed by paired t test. Results: The study completed full accrual with enrollment of 25 patients of whom 23 were evaluable for feasibility. The study achieved its primary end point with 15 patients (65%) completing therapy without treatment-related DLTs. DLTs included: fatigue (n = 2), pulmonary embolism, abdominal pain, supraventricular tachycardia, enteric fistula, hematuria, and dyspnea (n = 1 each). At RC, 5 patients (23%) had<pT2 disease. Analysis of pre- and posttreatment tumors demonstrated significantly decreased pSFK (P = 0.003) but no overall significant changes in Ki-67 or Cas3. In total, 4 cases demonstrated a nonsignificant decrease in Ki-67, of which 3 cases also demonstrated a decrease in pSFK and 2 cases had marginal increase in Cas3. Conclusions: Neo-D in miUCB patients was feasible and safe. Overall, significant inhibition of pSFK was observed without overall reduction of cellular proliferation or increase of apoptosis, although biologic anti-tumor activity may exist in a small subset of patients. These results highlight the potential utility of the neoadjuvant trial paradigm and suggest that clinical benefit of single-agent SFK inhibition in unselected patients with miUCB is unlikely.

Original languageEnglish (US)
Pages (from-to)4.e11-4.e17
JournalUrologic Oncology: Seminars and Original Investigations
Issue number1
StatePublished - Jan 1 2016
Externally publishedYes


  • Bladder
  • Dasatinib
  • Neoadjuvant therapy
  • Protein kinase inhibitors
  • Src-family kinases
  • Translational medical research
  • Urothelial carcinoma

ASJC Scopus subject areas

  • Oncology
  • Urology


Dive into the research topics of 'Neoadjuvant dasatinib for muscle-invasive bladder cancer with tissue analysis of biologic activity'. Together they form a unique fingerprint.

Cite this