Phase II Study of 5-Fluorouracil, Oxaliplatin plus Dasatinib (FOLFOX-D) in First-Line Metastatic Pancreatic Adenocarcinoma

Mené sur 44 patients atteints d'un adénocarcinome pancréatique de stade métastatique, cet essai de phase II évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité de l'ajout du dasatinib à une chimiothérapie de première ligne de type FOLFOX

Résumé en anglais

Background : Src tyrosine kinase activity is overexpressed in many human cancers, including metastatic pancreatic cancer (mPC). Dasatinib is a potent inhibitor of Src family of tyrosine kinases. This study was designed to investigate whether dasatinib can synergistically enhance anti-tumor effects of FOLFOX regimen (FOLFOX-D).

Methods : In this single arm, phase II study, previously untreated patients received dasatinib 150 mg oral daily on days 1–14, oxaliplatin 85 mg/m2 IV on day 1 every 14 days, leucovorin (LV) 400 mg/m2 IV on day 1 every 14 days, 5-fluorouracil (5FU) bolus 400 mg/m2 on day 1 every 14 days, and 5-FU continuous infusion 2,400 mg/m2 on day 1 every 14 days. Primary endpoint was progression-free survival (PFS) with pre-planned comparison to historical controls.

Results : Forty-four patients enrolled with an estimated median PFS of 4.0 (95% CI: 2.3-8.5) months, and overall survival (OS) of 10.6 (95% CI: 6.9-12.7) months. Overall response rate (ORR) was 22.7% (n=10): 1 patient (2.3%) with complete response (CR), and 9 patients (20.5%) with partial response. Fifteen patients (34.1%) had stable disease (SD). Nausea was the most common adverse event (AE) seen in 35 patients (79.5%).

Conclusion : The addition of dasatinib did not appear to add incremental clinical benefit to FOLFOX in untreated mPC patients.