Prognostic Impact of Relative Dose Intensity of Adjuvant Chemotherapy With S-1 on Pancreatic Ductal Adenocarcinoma

Abstract

Background/aim: Although adjuvant chemotherapy (AC) with S-1 is currently the standard treatment for pancreatic ductal adenocarcinoma (PDAC) in Japan, the associations between its relative dose intensity (RDI) and survival outcomes remain unclear.

Patients and methods: We reviewed 310 patients with PDAC who had undergone pancreatectomy from January 2014 to June 2020 at three institutions. Of these, patients who had received adjuvant S-1 monotherapy were analyzed. Patients who had died or developed recurrences within 6 months, or received neoadjuvant chemotherapy, were excluded from the analyses. Possible predictors of overall survival (OS), including RDI, were analyzed using Cox regression. The cutoff value for RDI was determined by receiver operating characteristic analysis.

Results: Ninety-four patients with a median age of 69 years (range=39-84 years) were analyzed. In the high-RDI group (RDI≥72.3%, n=74), the OS rates were 98.5% and 80.8% at 1 and 3 years, respectively, whereas in the low-RDI group (RDI <72.3%, n=20) they were 88.9% and 51.6%, respectively (p=0.001). By multivariate analysis, lymph node metastasis [hazard ratio (HR)=3.06; p=0.020], low RDI (HR=2.95; p=0.020), and time interval from surgery to initiation of AC > 51 days (HR=2.50; p=0.046) were independently associated with inferior OS. The combination of the latter two factors clearly stratified both OS and recurrence-free survival (p<0.001 and p=0.017, respectively).

Conclusion: Early initiation and maintenance of RDI of S-1 monotherapy after pancreatectomy may improve the OS of PDAC patients.

Keywords: Relative dose intensity; S-1; adjuvant chemotherapy; overall survival; pancreatic ductal adenocarcinoma.