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

Oncologist. 2021 Oct;26(10):825-e1674. doi: 10.1002/onco.13853. Epub 2021 Jun 23.

Abstract

Lessons learned: Preclinical studies have demonstrated that Src inhibition through dasatinib synergistically enhances the antitumor effects of oxaliplatin. In this phase II, single-arm study, FOLFOX with dasatinib in previously untreated patients with mPC only showed only modest clinical activity, with a progressive-free survival of 4 months and overall survival of 10.6 months. Continued investigation is ongoing to better understand the role of Src inhibition with concurrent 5-fluorouracil and oxaliplatin in a subset of exceptional responders.

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 antitumor 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 intravenous (IV) on day 1 every 14 days, leucovorin (LV) 400 mg/m2 IV on day 1 every 14 days, 5-fluorouracil (5-FU) 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 preplanned comparison to historical controls.

Results: Forty-four patients enrolled with an estimated median PFS of 4.0 (95% confidence interval [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): one patient (2.3%) with complete response (CR) and nine patients (20.5%) with partial response (PR). 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 patients with mPC.

Keywords: Dasatinib; FOLFOX; Metastatic pancreatic cancer; Src.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adenocarcinoma*
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Colorectal Neoplasms* / drug therapy
  • Dasatinib / pharmacology
  • Dasatinib / therapeutic use
  • Fluorouracil / therapeutic use
  • Humans
  • Leucovorin / therapeutic use
  • Oxaliplatin / pharmacology
  • Oxaliplatin / therapeutic use
  • Pancreatic Neoplasms* / drug therapy
  • Treatment Outcome

Substances

  • Oxaliplatin
  • Leucovorin
  • Dasatinib
  • Fluorouracil