Katsunori Shinozaki1, Takeshi Yamada2, Junichiro Nasu3, Toshihiko Matsumoto4, Yasuhiro Yuasa5, Takeshi Shiraishi6, Hiroaki Nagano7, Ichiro Moriyama8, Toshiyoshi Fujiwara9, Masashi Miguchi10, Ryosuke Yoshida11, Kimiyasu Nozaka12, Hiroaki Tanioka13, Takeshi Nagasaka13, Yasuro Kurisu14, Michiya Kobayashi15, Kenji Tsuchihashi16, Michio Inukai3, Takashi Kikuchi17, Tomohiro Nishina18. 1. Division of Clinical Oncology, Hiroshima Prefectural Hospital, 1-5-54 Ujinakanda, Hiroshima, 734-8530, Japan. k-shinozaki@hph.pref.hiroshima.jp. 2. Division of Gastroenterology, University of Tsukuba, Tsukuba, 305-8577, Japan. 3. Department of Internal Medicine, Okayama Saiseikai General Hospital, Okayama, 700-8501, Japan. 4. Department of Internal Medicine, Himeji Red Cross Hospital, Himeji, 670-8540, Japan. 5. Department of Surgery, Tokushima Red Cross Hospital, Tokushima, 773-8502, Japan. 6. Department of Medical Oncology, Matsuyama Red Cross Hospital, Matsuyama, 790-8520, Japan. 7. Department of Gastroenterological Surgery, Yamaguchi University Graduate School of Medicine, Ube, 755-8505, Japan. 8. Innovative Cancer Center, Shimane University Hospital, Izumo, 693-0021, Japan. 9. Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, 700-8530, Japan. 10. Department of Surgery, Hiroshima City Asa Citizens Hospital, Hiroshima, 731-0293, Japan. 11. Department of Surgery, Okayama Rosai Hospital, Okayama, 702-8055, Japan. 12. Department of Surgery, Sanin Rosai Hospital, Yonago, 683-8605, Japan. 13. Department of Clinical Oncology, Kawasaki Medical School Hospital, Kurashiki, 701-0192, Japan. 14. Department of Surgery, Hamada Medical Center, Hamada, 697-8511, Japan. 15. Cancer Treatment Center, Kochi Medical School Hospital, Nankoku, 783‑8505, Japan. 16. Department of Hematology, Oncology and Cardiovascular Medicine, Kyushu University Hospital, Fukuoka, 812-8582, Japan. 17. Foundation for Biomedical Research and Innovation at Kobe for Medical Innovation, Kobe, 650-0047, Japan. 18. Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, 791-0280, Japan.
Abstract
PURPOSE: FOLFOXIRI plus bevacizumab is regarded as a first-line therapeutic option for selected patients with metastatic colorectal cancer (mCRC). Our aim was to assess the efficacy and safety of induction treatment with FOLFOXIRI plus bevacizumab in patients with untreated mCRC harboring UGT1A1 wild (*1/*1), or single-hetero (*1/*6 or *1/*28) genotypes. METHODS: Twelve cycles of FOLFOXIRI plus bevacizumab were administered to patients with untreated mCRC. The primary endpoint was the overall response rate (ORR) assessed by central independent reviewers. Secondary endpoints included time to treatment failure (TTF), progression-free survival (PFS), overall survival (OS), relative dose intensity (RDI), R0 resection rate, and safety. The exploratory objectives were early tumor shrinkage (ETS) and depth of response (DoR). RESULTS: Of the 47 patients enrolled, 46 and 44 patients were eligible for the safety and efficacy analysis, respectively. The primary endpoint was met. The ORR was 63.6% (95% CI 47.8-77.6). At a median follow-up of 25.4 months, median TTF, PFS, and OS was 8.1, 15.5, and 34.4 months, respectively. The median RDI of 5-fluorouracil, irinotecan, oxaliplatin, and bevacizumab was 72, 69, 62, and 71%, respectively. R0 resection rate was 22.7%. Grade 3 or higher adverse events (≥ 10%) included neutropenia (65.2%), febrile neutropenia (26.1%), leukopenia (23.9%), anorexia (10.9%), nausea (10.9%), and diarrhoea (10.9%). No treatment-related deaths were observed. ETS and DoR were 70.5 and 45.4%, respectively. CONCLUSIONS: FOLFOXIRI plus bevacizumab induction treatment of Japanese patients was shown to be beneficial and manageable, although caution is required since the treatment causes febrile neutropenia.
PURPOSE:FOLFOXIRI plus bevacizumab is regarded as a first-line therapeutic option for selected patients with metastatic colorectal cancer (mCRC). Our aim was to assess the efficacy and safety of induction treatment with FOLFOXIRI plus bevacizumab in patients with untreated mCRC harboring UGT1A1 wild (*1/*1), or single-hetero (*1/*6 or *1/*28) genotypes. METHODS: Twelve cycles of FOLFOXIRI plus bevacizumab were administered to patients with untreated mCRC. The primary endpoint was the overall response rate (ORR) assessed by central independent reviewers. Secondary endpoints included time to treatment failure (TTF), progression-free survival (PFS), overall survival (OS), relative dose intensity (RDI), R0 resection rate, and safety. The exploratory objectives were early tumor shrinkage (ETS) and depth of response (DoR). RESULTS: Of the 47 patients enrolled, 46 and 44 patients were eligible for the safety and efficacy analysis, respectively. The primary endpoint was met. The ORR was 63.6% (95% CI 47.8-77.6). At a median follow-up of 25.4 months, median TTF, PFS, and OS was 8.1, 15.5, and 34.4 months, respectively. The median RDI of 5-fluorouracil, irinotecan, oxaliplatin, and bevacizumab was 72, 69, 62, and 71%, respectively. R0 resection rate was 22.7%. Grade 3 or higher adverse events (≥ 10%) included neutropenia (65.2%), febrile neutropenia (26.1%), leukopenia (23.9%), anorexia (10.9%), nausea (10.9%), and diarrhoea (10.9%). No treatment-related deaths were observed. ETS and DoR were 70.5 and 45.4%, respectively. CONCLUSIONS:FOLFOXIRI plus bevacizumab induction treatment of Japanese patients was shown to be beneficial and manageable, although caution is required since the treatment causes febrile neutropenia.
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