Phase II study of dasatinib (BMS-354825) in patients with metastatic adenocarcinoma of the pancreas.
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.


CONCLUSIONS
Single-agent dasatinib does not have clinical activity in metastatic PDAC.
University Hospitals Seidman Cancer Center and.
Cheng Ean
CE
Chee
Smitha
S
Krishnamurthi
Charles J
CJ
Nock
Neal J
NJ
Meropol
Joseph
J
Gibbons
Pingfu
P
Fu
Joseph
J
Bokar
Lois
L
Teston
Timothy
T
O'Brien
Vinay
V
Gudena
Amy
A
Reese
Mark
M
Bergman
Joel
J
Saltzman
John J
JJ
Wright
Afshin
A
Dowlati
Joanna
J
Brell
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D000069439:Dasatinib; D018572:Disease-Free Survival; D064420:Drug-Related Side Effects and Adverse Reactions / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D009362:Neoplasm Metastasis / Q000188:drug therapy* / Q000473:pathology; D009360:Neoplastic Cells, Circulating; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects; D013844:Thiazoles / Q000008:administration & dosage* / Q000009:adverse effects
D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D000069439:Dasatinib