BACKGROUND: Src, EphA2, and platelet-derived growth factor receptors α and β are dysregulated in pancreatic ductal adenocarcinoma (PDAC). METHODS: Dasatinib is an oral multitarget tyrosine kinase inhibitor that targets BCR-ABL, c-Src, c-KIT, platelet-derived growth factor receptor β, and EphA2. We conducted a phase II, single-arm study of dasatinib as first-line therapy in patients with metastatic PDAC. METHODS: Dasatinib (100 mg twice a day, later reduced to 70 mg twice a day because of toxicities) was orally administered continuously on a 28-day cycle. The primary endpoint was overall survival (OS). Response was measured using the Response Evaluation Criteria in Solid Tumors. Circulating tumor cells (CTCs) were also collected. RESULTS: Fifty-one patients enrolled in this study. The median OS was 4.7 months (95% confidence interval [CI]: 2.8-6.9 months). Median progression-free survival was 2.1 months (95% CI: 1.6-3.2 months). In 34 evaluable patients, the best response achieved was stable disease in 10 patients (29.4%). One patient had stable disease while on treatment for 20 months. The most common nonhematologic toxicities were fatigue and nausea. Edema and pleural effusions occurred in 29% and 6% of patients, respectively. The number of CTCs did not correlate with survival. CONCLUSION: Single-agent dasatinib does not have clinical activity in metastatic PDAC.
BACKGROUND:Src, EphA2, and platelet-derived growth factor receptors α and β are dysregulated in pancreatic ductal adenocarcinoma (PDAC). METHODS:Dasatinib is an oral multitarget tyrosine kinase inhibitor that targets BCR-ABL, c-Src, c-KIT, platelet-derived growth factor receptor β, and EphA2. We conducted a phase II, single-arm study of dasatinib as first-line therapy in patients with metastatic PDAC. METHODS:Dasatinib (100 mg twice a day, later reduced to 70 mg twice a day because of toxicities) was orally administered continuously on a 28-day cycle. The primary endpoint was overall survival (OS). Response was measured using the Response Evaluation Criteria in Solid Tumors. Circulating tumor cells (CTCs) were also collected. RESULTS: Fifty-one patients enrolled in this study. The median OS was 4.7 months (95% confidence interval [CI]: 2.8-6.9 months). Median progression-free survival was 2.1 months (95% CI: 1.6-3.2 months). In 34 evaluable patients, the best response achieved was stable disease in 10 patients (29.4%). One patient had stable disease while on treatment for 20 months. The most common nonhematologic toxicities were fatigue and nausea. Edema and pleural effusions occurred in 29% and 6% of patients, respectively. The number of CTCs did not correlate with survival. CONCLUSION: Single-agent dasatinib does not have clinical activity in metastatic PDAC.
Authors: Niharika B Mettu; Donna Niedzwiecki; Christel Rushing; Andrew B Nixon; Jingquan Jia; Sherri Haley; Wanda Honeycutt; Herbert Hurwitz; Johanna C Bendell; Hope Uronis Journal: Cancer Chemother Pharmacol Date: 2019-03-20 Impact factor: 3.333
Authors: Zipeng Lu; Maximilian Weniger; Kuirong Jiang; Stefan Boeck; Kai Zhang; Alexander Bazhin; Yi Miao; Jens Werner; Jan G D'Haese Journal: Target Oncol Date: 2018-08 Impact factor: 4.493
Authors: Peter Horvath; Nathalie Aulner; Marc Bickle; Anthony M Davies; Elaine Del Nery; Daniel Ebner; Maria C Montoya; Päivi Östling; Vilja Pietiäinen; Leo S Price; Spencer L Shorte; Gerardo Turcatti; Carina von Schantz; Neil O Carragher Journal: Nat Rev Drug Discov Date: 2016-09-12 Impact factor: 84.694