Hidetoshi Eguchi1,2, Yutaka Takeda3,4, Hidenori Takahashi5,4, Shin Nakahira6,4, Masaki Kashiwazaki7,4, Junzo Shimizu8,4, Daisuke Sakai9,4, Fumiaki Isohashi10, Hiroaki Nagano11,4, Masaki Mori12,4, Yuichiro Doki12,4. 1. Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. heguchi@gesurg.med.osaka-u.ac.jp. 2. Clinical Study Group of Osaka University, Hepato-Biliary-Pancreatic Group, Osaka, Japan. heguchi@gesurg.med.osaka-u.ac.jp. 3. Department of Surgery, Kansai Rosai Hospital, Amagasaki, Hyogo, Japan. 4. Clinical Study Group of Osaka University, Hepato-Biliary-Pancreatic Group, Osaka, Japan. 5. Department of Surgery, Osaka International Cancer Institute, Osaka, Japan. 6. Department of Surgery, Sakai City Medical Center, Osaka, Japan. 7. Department of Surgery, Osaka General Medical Center, Osaka, Japan. 8. Department of Surgery, Osaka Rosai Hospital, Osaka, Japan. 9. Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Osaka, Japan. 10. Department of Radiation Oncology, Graduate School of Medicine, Osaka University, Osaka, Japan. 11. Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan. 12. Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
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.
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.