Survival Outcomes of Patients With Borderline Resectable and Resectable Pancreatic Adenocarcinoma Treated With Neoadjuvant Short-Course Chemoradiotherapy With Capecitabine-Based vs. Gemcitabine-Based Concurrent Chemotherapy

Abstract

Purpose/Objective(s): Neoadjuvant chemoradiotherapy is a critical treatment for borderline resectable and resectable pancreatic adenocarcinoma ((B)RPC). The PREOPANC trials employ a short course chemoradiation (SCCRT) regimen of 3600 cGy in 15 fractions with concurrent gemcitabine (GEM)-based chemotherapy, but little is known about the relative efficacy of capecitabine (CAPE)-based concurrent chemotherapy in this population. We hypothesize that patients treated with SCCRT with CAPEbased concurrent chemotherapy will have superior overall survival (OS) compared to GEM-based strategies. Materials/Methods: Medical records were retrospectively reviewed at a single center for patients diagnosed with (B)RPC between 1/2005 and 12/ 2020. Patients treated with neoadjuvant SCCRT were included in the analysis. Descriptive statistics were quantified for baseline characteristics. OS was estimated using Kaplan-Meier estimates, statistical difference was determined using the log-rank test. Multivariate Cox proportional hazards analysis was conducted to estimate hazard ratios (HR) when controlling for confounding factors.Results: Thirty-one (n = 31) patients were included in the analysis. 71% of patients (n = 22) were treated with CAPE-based concurrent chemotherapy, while 29% of patients (n = 9) were treated with GEM-based concurrent chemotherapy. Median age at diagnosis was 65 (interquartile range (IQR): 60 to 71) for the CAPE group, compared to 66 (IQR: 63 to 71) for the GEM group, P = 0.414. 100% of patients in the CAPE group were borderline resectable, compared to 82% of patients in the GEM group, P = 0.171. 44% of patients in the CAPE group were treated with neoadjuvant FOL-FIRINOX, compared to 14% in the GEM group, P = 0.016. Patients treated with concurrent 5-CAPE-based chemotherapy had a longer median OS than other concurrent chemotherapy approaches: Not reached (95% confidence interval (CI): 24 to not reached) vs. 17 months (95% CI: 6 to 22 months), P < 0.0001. Multivariate Cox proportional hazards models, controlling for borderline vs. resectable status, age at diagnosis, and use of neoadjuvant FOLFIRINOX, demonstrated that CAPE-based concurrent chemotherapy had a HR of death of 0.081 (95% CI: 0.018 to 0.369, P = 0.0012) compared to GEM-based concurrent chemotherapy. Conclusion: Patients diagnosed with (B)RPC have many therapeutic options; this study suggests a benefit to CAPE-based concurrent chemotherapy when treating patients with SCCRT, even after controlling for significant confounding by greater use of neoadjuvant FOLFIRINOX with CAPE-based concurrent chemotherapy. SCCRT may be more effective with concurrent capecitabine instead of concurrent gemcitabine for (B) RPC.

Analysis of capecitabine metabolites in conjunction with digital autoradiography in a murine model of pancreatic cancer suggests extensive drug penetration through the tumor

“…23 The only direct comparison between gemcitabine and capecitabine comes from studies where they are given in combination with radiotherapy; these trials suggest a modest benefit for capecitabine over gemcitabine. 24,25 As there is no PET tracer for capecitabine, it will not be possible to identify individuals with homogenous capecitabine uptake in their tumors; however, 18 F-FAC may be used to identify patients with unfavorable gemcitabine distributions, and this could aid in stratifying patient groups. The tracer has previously been administered to volunteers, 26 and is scheduled to be administered to pancreatic cancer patients at Memorial Sloan Kettering.…”

“…For example, Yu and coworkers proposed gene expression profile‐based therapy administration as an optimal strategy 23 . The only direct comparison between gemcitabine and capecitabine comes from studies where they are given in combination with radiotherapy; these trials suggest a modest benefit for capecitabine over gemcitabine 24,25 . As there is no PET tracer for capecitabine, it will not be possible to identify individuals with homogenous capecitabine uptake in their tumors; however, 18 F‐FAC may be used to identify patients with unfavorable gemcitabine distributions, and this could aid in stratifying patient groups.…”