In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 3_suppl ( 2014-01-20), p. 319-319
Abstract:
319 Background: Triplet drug therapy is now a standard for metastatic pancreatic cancer (mPCa) but limited in use due to toxicity. Src is constitutively active in mPCa and associated with increased chemoresistance. Src inhibition increases oxaliplatin (ox) activity. Inhibition of Src reduces tumor expression of thymidylate synthase with subsequent 5FU chemoresistance reversal. Dasatinib (D) is an oral multi-tyrosine kinase inhibitor (TKI) capable of inhibiting Src. Demonstrating activity of this triplet combination therapy in mPCa represents a scientifically rational approach to a clinical unmet need. Methods: Eligible pts have biopsy proven, RECIST measurable disease with no prior therapy for met disease and at least 6 months since completing adjuvant therapy, ECOG PS 0-2 and adequate organ function. Pts received standard doses of mFOLFOX6 chemotherapy (5-FU/LV 400mg/m 2 bolus and Ox 85 mg/m 2 D1; 5-FU 2,400 mg/m 2 CIVI x 46h D1-2) with continuous D (150 mg PO daily) repeated q14d with tumor assessments q8w. The primary endpoint is progression-free survival (PFS) with secondary endpoints of objective and biochemical response rates, freedom from mets, overall survival (OS), toxicity, and quality of life. Sample size was based on a 50% improved median PFS from 4 (historical) to 6 months (m). Results: 14 of 42 planned pts have received therapy and are included in this report. Baseline pt demographics are in the table. 10 pts (71%) had a grade 3 AE and 1 (7%; sepsis) had a grade 4 AE. There were no grade 5 toxicities. Most common grade 3 AEs included anemia (29%), hyponatremia (29%), neutropenia (21%) and fatigue (21%). Conclusions: Enrollment continues with ongoing toxicity and efficacy monitoring of this targeted combination. Exploratory tissue and serum correlative analyses to identify predictors of response are planned. Clinical trial information: NCT01652976. [Table: see text]
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2014.32.3_suppl.319
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2014
detail.hit.zdb_id:
2005181-5
