Induction Chemotherapy With FOLFIRINOX Followed by Chemoradiation With Gemcitabine in Patients With Borderline-Resectable Pancreatic Ductal Adenocarcinoma

Ana Acuna-Villaorduna, Viswanathan Shankar, Michael Wysota, Amanda Jirgal, Rafi Kabarriti, Sarah Bellemare, Inessa Goldman, Andreas Kaubisch, Santiago Aparo, Sanjay Goel, Jennifer Chuy, Ana Acuna-Villaorduna, Viswanathan Shankar, Michael Wysota, Amanda Jirgal, Rafi Kabarriti, Sarah Bellemare, Inessa Goldman, Andreas Kaubisch, Santiago Aparo, Sanjay Goel, Jennifer Chuy

Abstract

Introduction: Perioperative therapy is standard for patients with borderline-resectable pancreatic ductal adenocarcinoma (BR-PDAC); however, an optimal neoadjuvant regimen is lacking. We assessed the efficacy of FOLFIRINOX chemotherapy followed by gemcitabine-based chemoradiation as preoperative therapy.

Methods: Patients received 4 cycles of FOLFIRINOX, followed by 6-weekly gemcitabine with concomitant intensity-modulated radiation. The primary endpoint was the R0 resection rate. Secondary outcomes included resection rate, overall-response, overall survival (OS), progression-free survival (PFS), and tolerability. The trial was terminated early due to slow accrual. A Simon's optimal two-stage phase II trial single arm design was used. The primary hypothesis of treatment efficacy was tested using a multistage group sequential inference procedure. The secondary failure time analysis endpoints were assessed using the Kaplan-Meier procedure and the Cox regression model.

Results: A total of 22 patients enrolled in the study, 18 (81.8%) completed neoadjuvant treatment. The bias corrected R0 rate was 55.6% (90% CI: 33.3, 68.3; P value = .16) among patients that received at least 1 cycle of FOLFIRINOX and was 80% among patients that underwent surgery. The median OS was 35.1 months. The median PFS among patients that underwent surgery was 34 months.

Conclusion: An R0 resection rate of 55.6% is favorable. Neoadjuvant FOLFIRINOX followed by concomitant Gemcitabine with radiation was well-tolerated. NCT01897454.

Keywords: borderline; neoadjuvant; pancreas.

Conflict of interest statement

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Graphical Abstract
Graphical Abstract
Figure 1.
Figure 1.
Flowchart of participants with borderline-resectable pancreatic ductal adenocarcinoma enrolled in the trial.
Figure 2.
Figure 2.
(A) Tumor response (n = 19) and (B) Clinical Outcomes after neoadjuvant treatment with FOLFIRINOX followed by Gemcitabine/RT (n = 22) in patients with borderline-resectable pancreatic cancer who underwent surgery.
Figure 3.
Figure 3.
Recurrence Free-Survival and Overall Survival of patients with BR-PDAC treated with neoadjuvant FOLFIRINOX followed by Gemcitabine/RT (n = 22)

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