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Journal of Gastroenterology

, Volume 54, Issue 2, pp 194–203 | Cite as

A single-arm, phase II trial of neoadjuvant gemcitabine and S1 in patients with resectable and borderline resectable pancreatic adenocarcinoma: PREP-01 study

  • Fuyuhiko MotoiEmail author
  • Sohei Satoi
  • Goro Honda
  • Keita Wada
  • Hiroyuki Shinchi
  • Ippei Matsumoto
  • Masayuki Sho
  • Akihiko Tsuchida
  • Michiaki Unno
  • For the Study Group of Preoperative therapy for Pancreatic cancer (PREP)
Original Article—Liver, Pancreas, and Biliary Tract
  • 401 Downloads

Abstract

Background

Neoadjuvant chemotherapy (NAC) represents a promising alternative to pancreatic ductal adenocarcinoma (PDAC) planned resection, but the survival impact remains undefined. To assess the feasibility and survival outcomes of NAC with gemcitabine and S1 (GS) for PDAC planned resection by prospective study.

Methods

Patients with resectable or borderline resectable PDAC received 2 cycles of NAC-GS and were offered curative resection followed by gemcitabine adjuvant. The primary endpoint was 2-year overall survival (OS). Adverse events during NAC, radiological and tumor marker responses, resection rate, and surgical safety were evaluated as secondary endpoints (UMIN000004148).

Results

We enrolled 104 patients between 2010 and 2012, with 101 patients treated using NAC-GS as the full analysis set (FAS). Of the 101 patients, 88% received the planned 2 cycles of NAC. Grade 3 neutropenia was common (35%). Radiological partial response and decreased carbohydrate antigen 19-9 concentration (> 50% decrease) were noted in 13% and 41%, respectively. R0/1 resections with M0 were performed in 65 patients without surgical mortality. Of the 65 patients, 44 received planned gemcitabine adjuvant for 6 months as the on-protocol cohort. The primary endpoint for the 2-year OS rate was 55.9% in the FAS (n = 101) and 74.6% in the on-protocol cohort (n = 44).

Conclusions

NAC-GS was feasible and actively prolonged survival following PDAC planned resection. Randomized control trials are needed to further clarify the survival benefit of NAC-GS in addition to surgery followed by adjuvant therapy.

Keywords

Neoadjuvant Chemotherapy Pancreatic cancer Surgery 

Notes

Acknowledgements

This work was supported in part by Grants-in-Aid for Scientific Research 24592018 from the Japan Society for the Promotion of Science. We would like to express sincere appreciation to Drs. M. Kurata, H. Yanagimoto, H. Toyama, Y. Nagakawa, K. Maemura, Y. Mataki, T. Akahori, S. Kinoshita, H. Terashima, A. Horiguchi, Y. Ohtsuka, A. Nanashima, K. Kanemitsu, H. Ohigashi, M. Tani, T. Takahara, H. Shiomi, I. Endo, H. Suzuki, T. Rikiyama, H. Ikoma, M. Yasunaga, K. Nakamura, S. Egawa, Y. Katayose, K. Nakagawa, K. Okada, and S. Ottomo as clinical investigators in the study group of preoperative therapy for pancreatic cancer (PREP).

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest.

Supplementary material

535_2018_1506_MOESM1_ESM.pptx (123 kb)
Supplemental Figure 1. Overall survival curve for PDAC planned NAC-GS according to the resectability status. 1A. Survival comparison by intention-to-treat analysis. Median OS of the patients with R PDAC (n=63, solid line) was 39.2 months, which was longer but not significant than that of the patients with BR PDAC (n=38, 21.1 months, broken line)(p=0.35). The 2-year OS of R and BR PDAC were 60.4% and 48.6%, respectively. 1B. Survival comparison by on-protocol analysis. The 2-year OS of R PDAC (n=29, solid line) and BR PDAC (n=15, broken line) were 78.9% and 66.7%, respectively (p=0.70) (PPTX 123 kb)
535_2018_1506_MOESM2_ESM.pptx (115 kb)
Supplemental Figure 2. Overall survival curve for PDAC planned NAC-GS according to cycles receiving postoperative adjuvant treatment. 1A. Survival comparison of on-protocol cohort with or without completion of postoperative adjuvant treatment. The 2-year OS of the patients receiving 6 cycles (n=26, solid line) and less than 6 cycles (n=18, broken line) of gemcitabine adjuvant were 84.4% and 60.6%, respectively (p=0.22). 2B. Survival comparison of on-protocol cohort with 4 and over cycles or less than 4 cycles of postoperative adjuvant treatment. The 2-year OS of the patients receiving 4 and over cycles (n=30, solid line) and less than 4 cycles (n=14, broken line) of gemcitabine adjuvant were 86.5% and 49.0%, respectively (p=0.0067) (PPTX 114 kb)
535_2018_1506_MOESM3_ESM.pdf (663 kb)
Supplementary material 3 (PDF 664 kb)

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Copyright information

© Japanese Society of Gastroenterology 2018

Authors and Affiliations

  • Fuyuhiko Motoi
    • 1
    Email author
  • Sohei Satoi
    • 2
  • Goro Honda
    • 3
  • Keita Wada
    • 4
  • Hiroyuki Shinchi
    • 5
  • Ippei Matsumoto
    • 6
  • Masayuki Sho
    • 7
  • Akihiko Tsuchida
    • 8
  • Michiaki Unno
    • 1
  • For the Study Group of Preoperative therapy for Pancreatic cancer (PREP)
  1. 1.Department of SurgeryTohoku University Graduate School of MedicineSendaiJapan
  2. 2.Department of SurgeryKansai Medical UniversityHirakata CityJapan
  3. 3.Department of SurgeryTokyo Metropolitan Cancer and Infectious Diseases Center Komagome HospitalTokyoJapan
  4. 4.Department of SurgeryTeikyo University School of MedicineTokyoJapan
  5. 5.Department of Digestive Surgery, Breast and Thyroid SurgeryKagoshima UniversityKagoshimaJapan
  6. 6.Department of SurgeryKindai University Faculty of MedicineOsaka-SayamaJapan
  7. 7.Department of SurgeryNara Medical UniversityKashiharaJapan
  8. 8.Department of Gastrointestinal and Pediatric SurgeryTokyo Medical UniversityTokyoJapan

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