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

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.

• Authors: Thomas J George, Azka Ali, Yu Wang, Ji-Hyun Lee, Alison M Ivey, David DeRemer, Karen C Daily, Carmen J Allegra, Steven J Hughes, Z Hugh Fan, Miles E Cameron, Andrew R Judge, Jose G Trevino
• Journal: The oncologist (Oncologist) Vol. 26 Issue 10 Pg. 825-e1674 (10 2021) ISSN: 1549-490X [Electronic] England
• PMID: 34101295 (Publication Type: Clinical Trial, Phase II, Journal Article)
• Copyright: © AlphaMed Press; the data published online to support this summary are the property of the authors.

Chemical References

• Oxaliplatin
• Leucovorin
• Dasatinib
• Fluorouracil

Topics

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