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A Prospective, Open-Label, Multicenter Phase 2 Trial of Neoadjuvant Therapy Using Full-Dose Gemcitabine and S-1 Concurrent with Radiation for Resectable Pancreatic Ductal Adenocarcinoma

  • Pancreatic Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Neoadjuvant therapy reportedly shows only marginal clinical benefit in pancreatic ductal adenocarcinoma (PDAC), especially in resectable cases. However, with more effective regimens, neoadjuvant therapy may become a standard of care for resectable cases. A prospective, open-label, multicenter phases 1 and 2 trial of neoadjuvant therapy was conducted using full-dose gemcitabine and S-1 concurrently with 50.4 Gy of radiation therapy (GSRT) for resectable PDAC. This report describes the phase 2 results.

Methods

The phase 2 part of this study enrolled 57 patients with cytologically or histologically proven PDAC deemed resectable based on imaging before neoadjuvant therapy. These patients received GSRT. After reevaluation by computed tomography scan, surgical exploration was performed, followed by adjuvant therapy. According to the prescribed protocol of the clinical trial, statistical analyses included 57 phase 2 patients and 6 phase 1 patients who received the same dosage as in phase 2.

Results

This trial enrolled 63 patients (42 men and 21 women) with a median age of 70 years. Leukopenia or neutropenia of grade 3 or higher occurred for 79% of the patients, but no other severe adverse events were observed. Among the 63 patients, 54 underwent surgical resection. Intention-to-treat analysis of the 63 patients showed an excellent median survival time lasting as long as 55.3 months. The patients who completed neoadjuvant therapy, surgery, and adjuvant therapy had a 5-year survival rate of 56.6%.

Conclusions

This regimen showed outstanding clinical efficacy with acceptable tolerability for patients with resectable PDAC.

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Authors and Affiliations

  1. Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan

    Hidetoshi Eguchi MD, Masaki Mori MD & Yuichiro Doki MD

  2. Department of Surgery, Kansai Rosai Hospital, Amagasaki, Hyogo, Japan

    Yutaka Takeda MD

  3. Department of Surgery, Osaka International Cancer Institute, Osaka, Japan

    Hidenori Takahashi MD

  4. Department of Surgery, Sakai City Medical Center, Osaka, Japan

    Shin Nakahira MD

  5. Department of Surgery, Osaka General Medical Center, Osaka, Japan

    Masaki Kashiwazaki MD

  6. Department of Surgery, Osaka Rosai Hospital, Osaka, Japan

    Junzo Shimizu MD

  7. Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Osaka, Japan

    Daisuke Sakai MD

  8. Department of Radiation Oncology, Graduate School of Medicine, Osaka University, Osaka, Japan

    Fumiaki Isohashi MD

  9. Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan

    Hiroaki Nagano MD

  10. Clinical Study Group of Osaka University, Hepato-Biliary-Pancreatic Group, Osaka, Japan

    Hidetoshi Eguchi MD, Yutaka Takeda MD, Hidenori Takahashi MD, Shin Nakahira MD, Masaki Kashiwazaki MD, Junzo Shimizu MD, Daisuke Sakai MD, Hiroaki Nagano MD, Masaki Mori MD & Yuichiro Doki MD

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  1. Hidetoshi Eguchi MD
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Correspondence to Hidetoshi Eguchi MD.

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Eguchi, H., Takeda, Y., Takahashi, H. et al. A Prospective, Open-Label, Multicenter Phase 2 Trial of Neoadjuvant Therapy Using Full-Dose Gemcitabine and S-1 Concurrent with Radiation for Resectable Pancreatic Ductal Adenocarcinoma. Ann Surg Oncol 26, 4498–4505 (2019). https://doi.org/10.1245/s10434-019-07735-8

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