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

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
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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.

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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).

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Authors and Affiliations

  1. Department of Surgery, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan

    Fuyuhiko Motoi & Michiaki Unno

  2. Department of Surgery, Kansai Medical University, 2-5-1 Shin-machi, Hirakata City, Osaka, 573-1010, Japan

    Sohei Satoi

  3. Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8677, Japan

    Goro Honda

  4. Department of Surgery, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8606, Japan

    Keita Wada

  5. Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan

    Hiroyuki Shinchi

  6. Department of Surgery, Kindai University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka, 589-8511, Japan

    Ippei Matsumoto

  7. Department of Surgery, Nara Medical University, 840 Shijo-Cho, Kashihara, Nara, 634-8521, Japan

    Masayuki Sho

  8. Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan

    Akihiko Tsuchida

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  1. Fuyuhiko Motoi
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  2. Sohei Satoi
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  4. Keita Wada
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Consortia

For the Study Group of Preoperative therapy for Pancreatic cancer (PREP)

  • 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
  •  & S. Ottomo

Corresponding author

Correspondence to Fuyuhiko Motoi.

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Conflict of interest

The authors declare no conflicts of interest.

Electronic supplementary material

Below is the link to the electronic supplementary material.

535_2018_1506_MOESM1_ESM.pptx

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

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)

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Motoi, F., Satoi, S., Honda, G. et al. A single-arm, phase II trial of neoadjuvant gemcitabine and S1 in patients with resectable and borderline resectable pancreatic adenocarcinoma: PREP-01 study. J Gastroenterol 54, 194–203 (2019). https://doi.org/10.1007/s00535-018-1506-7

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  • DOI: https://doi.org/10.1007/s00535-018-1506-7

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