A randomized phase II trial of adjuvant chemotherapy with S-1 versus S-1 and gemcitabine (GS) versus gemcitabine alone (GEM) in patients with resected pancreatic cancer (CAP-002 study).

Abstract

4056 Background: Although the adjuvant therapy using GEM is now the standard therapy for patients with resected pancreatic cancer (PC), the prognosis still remains poor. Resent study demonstrated the non-inferiority of S-1 and superiority of GS to GEM with respect to progression free survival in patients with unresectable pancreatic cancer. Methods: Patients with invasive ductal PC who underwent radical surgery were enrolled. After stratification for R0/1, stage and institution, patients were randomized to receive GEM (GEM 1g/ m2, iv, d1, 8, and 15, q4w X12), S-1 (80/100/120mg/day based on BSA, po, d1-14, q3w X 16) or GS (S-1 60/80/100mg/day based on BSA po, d1-14 plus GEM 1g/ m2, iv, d8, 15, q3w X 16) within 8weeks after operation. Eligibility included histological residual tumor (R) 0 or 1, and no previous chemo- or/and radiation therapy. Primary endpoint was 2y disease free survival (DFS) rate and secondary endpoints included overall survival (OS), and safety. Results: Between January 2007 and October 2010, 96 patients were randomized into the three arms of the trial (32 pts to each group). Patients’ characteristics were well balanced (GEM/S-1/GS) with regard to age (66/67/66y), tumor location (head 66/69/75%), tumor status (T3+4 88/78/91%), and nodal status (positive 75/69/75%). Until November 2012, 74 events (77%) have occurred for DFS. Two year DFS rate was 24.2%, 28.1% and 34.4% in GEM, S-1 and GS, respectively and there was no significant difference between groups. The median OS was 21m in GEM, 26m in S-1 and 27.9m in GS (Log rank test: N.S.). Grade 3/4 toxicities in GEM/S-1/GS were hematological 63/10/74% and non-hematological 17/10/23%, respectively. No treatment related death was observed during the study. Conclusions: S-1 and GS provided similar efficacy to GEM as the adjuvant chemotherapy for resected PC. According to the results, S-1 and GS is the adequate combination for phase III trial to examine the efficacy of adjuvant chemotherapy for PC. Clinical trial information: UMIN000002000.

Meta-analysis on resected pancreatic cancer: a comparison between adjuvant treatments and gemcitabine alone

“…1 . Of the nine trials, three trials are excluded because one reported by Tempero et al [ 20 ] is ongoing trial, the other two by Sinn et al [ 21 ] and Yoshitomi et al [ 22 ] can not obtained detailed data. Both investigators finally agreed to include 6 RCTs in the meta-analysis.…”

“…At the same dose, Asians had lower toxic reaction to S-1 than Europeans due to different metabolism. Furthermore, the CAP-002 study [ 22 ] also reported that S-1and Gem+S-1(GS) provided similar efficacy to Gem as the adjuvant chemotherapy for resected pancreatic cancer. Two year DFS rate was 24.2%, 28.1% and 34.4% in Gem, S-1 and GS, respectively and the median OS was 21 m in Gem, 26 m in S-1 and 27.9 m in GS.…”

Chemoradiotherapy for locally advanced pancreatic cancer patients: is it still an open question?

“…The quest for optimal adjuvant therapy continues, and the use of the oral agent S-1 in an adjuvant setting represents one of the newer successes in this direction [ 34 ]. The result of the Fukutomi et al .…”