Related Experiment Video
Updated: Apr 4, 2026
An Orthotopic Bladder Tumor Model and the Evaluation of Intravesical saRNA Treatment
Published on: July 28, 2012
Neoadjuvant dasatinib for muscle-invasive bladder cancer with tissue analysis of biologic activity
Noah M Hahn1, Beatrice S Knudsen2, Siamak Daneshmand3
1Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN; Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD.
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 100mg 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
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.
Insights
Neoadjuvant dasatinib (Neo-D) was feasible and safe in muscle-invasive urothelial carcinoma of the bladder (miUCB) patients. While it inhibited SRC-family kinases (SFK), it did not significantly reduce proliferation or increase apoptosis in most patients.
Area of Science:
- Oncology
- Urothelial Carcinoma Research
- Pharmacological Studies
Background:
- Preclinical models show dasatinib, an SRC-family kinase (SFK) inhibitor, has activity in urothelial carcinoma.
- Muscle-invasive urothelial carcinoma of the bladder (miUCB) is a significant clinical challenge.
- Neoadjuvant therapy aims to improve outcomes before radical cystectomy (RC).
Purpose of the Study:
- To determine the feasibility and biologic activity of neoadjuvant dasatinib (Neo-D) in patients with miUCB.
- To assess Neo-D's safety profile and effect on tumor markers preceding radical cystectomy (RC).
Main Methods:
- A prospective, multisite phase II clinical trial.
- Patients with resectable miUCB received Neo-D (100mg daily) for 28±7 days before RC.
- Primary endpoint: feasibility (≥60% completing therapy without dose-limiting toxicity). Tumor biomarkers (pSFK, Ki-67, Cas-3) were analyzed pre- and post-treatment.
Main Results:
- The study met its primary endpoint: 65% of patients completed Neo-D without dose-limiting toxicity.
- Significant decrease in phosphorylated SFK (pSFK) was observed (P = 0.003).
- No significant overall changes in Ki-67 or cleaved caspase-3 (Cas3) were detected, though a subset showed potential anti-tumor activity.
Conclusions:
- Neoadjuvant dasatinib (Neo-D) is feasible and safe in miUCB patients.
- Significant SFK inhibition occurred, but overall anti-proliferative or pro-apoptotic effects were not evident.
- Single-agent SFK inhibition in unselected miUCB patients is unlikely to provide clinical benefit.
