Vol.:(0123456789) 1 3 Medical Oncology (2018) 35:100 https://doi.org/10.1007/s12032-018-1158-8 ORIGINAL PAPER A phase II trial of gemcitabine, S-1 and LV combination (GSL) neoadjuvant chemotherapy for patients with borderline resectable and locally advanced pancreatic cancer Kei Saito 1  · Hiroyuki Isayama 1,2  · Yoshihiro Sakamoto 3  · Yousuke Nakai 1  · Kazunaga Ishigaki 1  · Mariko Tanaka 4  · Takeyuki Watadani 5  · Junichi Arita 3  · Naminatsu Takahara 1  · Suguru Mizuno 1  · Hirofumi Kogure 1  · Hideaki Ijichi 1  · Keisuke Tateishi 1  · Minoru Tada 1  · Kiyoshi Hasegawa 3  · Masashi Fukayama 4  · Norihiro Kokudo 3  · Kazuhiko Koike 1 Received: 2 May 2018 / Accepted: 24 May 2018 © Springer Science+Business Media, LLC, part of Springer Nature 2018 Abstract There has been a pressing need to develop optimal regimen for neoadjuvant chemotherapy (NAC) for pancreatic cancer (PC). The safety and efficacy of gemcitabine, S-1, and LV combination (GSL) therapy as NAC for borderline resectable (BR) and locally advanced (LA) PC was evaluated in this phase II study. Patients with pathologically proven BR or LA PC were enrolled and gemcitabine 1000 mg/m 2 by 30-min infusion on day 1, S-1 40 mg/m 2 orally twice daily, and LV 25 mg orally twice daily on days 1–7 every 2 weeks were provided, and evaluation by CT every 2 courses was performed. The primary end point was R0 resection rate, and the secondary endpoints were resection rate, response rate, adverse events, surgical outcomes, and survival. Twenty-four patients with PC (21 BR and 3 LA) were enrolled. Response rate and disease control rate of NAC were 17.4 and 87.0%. Grade 3 and 4 toxicities involved neutropenia (34.8%), anorexia (17.4%), and mucositis (17.4%). Serum CA19-9 level decreased by 52.2%. Resection rate was 60.9% after the median of 4 cycles and R0 resection rate was 76.5% in patients undergoing laparotomy. NAC-GSL is a feasible treatment option for BR and LAPC. Keywords Pancreatic cancer · Neoadjuvant chemotherapy · Gemcitabine · S-1 · Leucovorin Introduction Pancreatic cancer (PC) is the fourth leading cause of cancer death in Japan. Although surgical resection is the only cure, only 20% of patients are surgical candidates, and the overall 5-year survival rate is less than 5% [1]. In patients with met- astatic PC, the prognosis is quite poor with median overall survival (OS) less than 12 months despite the advancement of intensive chemotherapy [2–6]. Even in resectable PC, median OS is only 2 years due to a high recurrence rate [7]. Recently, the criteria of resectability status are widely used for the management of PC [8], and borderline resect- able PC (BRPC), an intermediate category between resect- able and locally advanced PC (LAPC), is defined as cancer with tumors involving the two vascular systems of the arte- rial axis and the portal vein or the superior mesenteric vein. Patients with BRPC and LAPC who received upfront sur- gery could have poor survival for two reasons: Early recur- rence due to occult metastases and a low completion rate of adjuvant chemotherapy after invasive pancreatic resection. Therefore, neoadjuvant chemotherapy (NAC) is intensively Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12032-018-1158-8) contains supplementary material, which is available to authorized users. * Hiroyuki Isayama isayama-tky@umin.ac.jp 1 Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo 113-8655, Japan 2 Department of Gastroenterology, Graduate School of Medicine, Juntendo University, Tokyo, Japan 3 Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan 4 Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan 5 Department of Radiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan