Hitoshi Shibuya1,2, Susumu Hijioka3,4, Yasunari Sakamoto5, Tetsuhide Ito6,7, Keijiro Ueda8, Izumi Komoto9, Noritoshi Kobayashi10, Atsushi Kudo11, Hiroaki Yasuda12, Hayato Miyake12, Junichi Arita13, Sho Kiritani13, Masafumi Ikeda14, Hiroshi Imaoka14, Makoto Ueno15, Satoshi Kobayashi15, Mitsuhiro Furuta16, Yoshikuni Nagashio17, Gou Murohisa18, Taku Aoki19, Shigemi Matsumoto20, Masayo Motoya21, Nobuaki Azemoto22, Jun Itakura23, Shigeru Horiguchi24, Tatsuji Yogi25, Tetsuro Kawagoe26, Youichi Miyaoka27, Fumito Imamura28, Michio Senju29, Hitoshi Arioka30, Kazuo Hara1, Masayuki Imamura9, Takuji Okusaka5. 1. Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan. 2. Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan. 3. Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan. shijioka@ncc.go.jp. 4. Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. shijioka@ncc.go.jp. 5. Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. 6. Neuroendocrine Tumor Center, Fukuoka Sanno Hospital, Fukuoka, Japan. 7. Internal University of Health and Welfare, Fukuoka, Japan. 8. Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 9. Department of Surgery, Kansai Electric Power Hospital, Osaka, Japan. 10. Department of Oncology, Yokohama City University Graduate School of Medicine, Kanagawa, Japan. 11. Department of Hepato-Biliary-Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan. 12. Division of Gastroenterology and Hepatology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan. 13. Hepato-Biliary and Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan. 14. Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Chiba, Japan. 15. Department of Gastroenterology, Hepatobiliary and Pancreatic Medical Oncology Division, Kanagawa Cancer Center, Kanagawa, Japan. 16. Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan. 17. Department of Hepato-Biliary-Pancreatology, National Kyushu Cancer Center, Fukuoka, Japan. 18. Department of Gastroenterology, Seirei Hamamatsu General Hospital, Shizuoka, Japan. 19. Second Department of Surgery, Dokkyo Medical University, Tochigi, Japan. 20. Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. 21. Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan. 22. Department of Gastroenterology, Shikoku Cancer Center, Matsuyama, Japan. 23. Department of Gastrointestinal, Breast and Endocrine Surgery, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan. 24. Department of Gastroenterology and Hepatology, Okayama University Hospital, Okayama, Japan. 25. Department of Infectious, Respiratory, and Digestive Medicine, Control and Prevention of Infectious Diseases, Faculty of Medicine, University of the Ryukyu, Okinawa, Japan. 26. Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine, Tokyo, Japan. 27. Department of Endoscopy, Shimane Prefectural Central Hospital, Shimane, Japan. 28. Hitachi, Ltd., Hitachinaka General Hospital, Ibaraki, Japan. 29. Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan. 30. Department of Medical Oncology, Yokohama Rosai Hospital, Kanagawa, Japan.
Abstract
PURPOSE: Streptozocin (STZ) is a key agent for treating advanced pancreatic neuroendocrine tumors (pNET). Most STZ regimens for pNET are daily and also include 5-fluorouracil (5FU), whereas STZ monotherapy and weekly regimens have also been applied in daily practice in Japan. The present study aimed to evaluate responses to weekly regimens and to STZ monotherapy, and to identify a predictive marker of a response to STZ. METHODS: Clinical data regarding STZ-based chemotherapy for pNET were collected between 2015 and 2017 at 25 facilities. We analyzed the effects, safety, progression-free survival (PFS), and factors that correlate with responses to STZ. RESULTS: The overall objective response rate (ORR) of 110 patients who underwent STZ-based chemotherapy (monotherapy, 81.8%; weekly regimen 46.4%) was 21.8%, and PFS was 9.8 months. The ORR of weekly vs. daily regimens was 21.6 vs. 22.0% (P = 1.000), and that of monotherapy vs. combination therapy was 21.1 vs. 25.0% (P = 0.766). A Ki67 proliferation index (Ki67) of > 5% was a predictive marker of a response to STZ (P = 0.017), whereas regimen type, mono- or combination therapy, treatment line and liver tumor burden were not associated with responses. The frequencies of Grade ≥ 3 nausea and hematological adverse events were significantly lower for monotherapy than combination therapy (P = 0.032). CONCLUSIONS: The effects of weekly STZ monotherapy on pNET are comparable to those previously reported and the toxicity profile was acceptable. Ki67 > 5% was the sole predictive marker of an objective response.
PURPOSE:Streptozocin (STZ) is a key agent for treating advanced pancreatic neuroendocrine tumors (pNET). Most STZ regimens for pNET are daily and also include 5-fluorouracil (5FU), whereas STZ monotherapy and weekly regimens have also been applied in daily practice in Japan. The present study aimed to evaluate responses to weekly regimens and to STZ monotherapy, and to identify a predictive marker of a response to STZ. METHODS: Clinical data regarding STZ-based chemotherapy for pNET were collected between 2015 and 2017 at 25 facilities. We analyzed the effects, safety, progression-free survival (PFS), and factors that correlate with responses to STZ. RESULTS: The overall objective response rate (ORR) of 110 patients who underwent STZ-based chemotherapy (monotherapy, 81.8%; weekly regimen 46.4%) was 21.8%, and PFS was 9.8 months. The ORR of weekly vs. daily regimens was 21.6 vs. 22.0% (P = 1.000), and that of monotherapy vs. combination therapy was 21.1 vs. 25.0% (P = 0.766). A Ki67 proliferation index (Ki67) of > 5% was a predictive marker of a response to STZ (P = 0.017), whereas regimen type, mono- or combination therapy, treatment line and liver tumor burden were not associated with responses. The frequencies of Grade ≥ 3 nausea and hematological adverse events were significantly lower for monotherapy than combination therapy (P = 0.032). CONCLUSIONS: The effects of weekly STZ monotherapy on pNET are comparable to those previously reported and the toxicity profile was acceptable. Ki67 > 5% was the sole predictive marker of an objective response.
Authors: Elettra Merola; Andrea Michielan; Umberto Rozzanigo; Marco Erini; Sandro Sferrazza; Stefano Marcucci; Chiara Sartori; Chiara Trentin; Giovanni de Pretis; Franca Chierichetti Journal: World J Gastrointest Surg Date: 2022-02-27