PMID- 38374403 OWN - NLM STAT- Publisher LR - 20240220 IS - 1432-0843 (Electronic) IS - 0344-5704 (Linking) DP - 2024 Feb 19 TI - Multicenter randomized phase II study on S-1 and oxaliplatin therapy as an adjuvant after hepatectomy for colorectal liver metastases (YCOG1001). LID - 10.1007/s00280-024-04648-6 [doi] AB - PURPOSE: The high recurrence rate of colorectal cancer liver metastasis (CRCLM) after surgery remains a crucial problem. However, adjuvant chemotherapy after hepatectomy for CRCLM has not yet been established. This study evaluated the efficacy of adjuvant therapy with S-1 and oxaliplatin (SOX). METHODS: In a multicenter, randomized, phase II study, patients undergoing curative resection of CRCLM were randomly enrolled in a 1:1 ratio to either the low- or high-dose group. S-1 and oxaliplatin were administered from days 1 to 14 of a 3-week cycle as a 2-h infusion every 3 weeks. The dose of S-1 was fixed at 80 mg/m(2). The doses in the low- and high-dose oxaliplatin groups were 100 mg/m(2) (low-dose group) and 130 mg/m(2) (high-dose group), respectively. This treatment was repeated eight times. The primary endpoint was the rate of discontinuation owing to toxicity. The secondary endpoints were the relapse-free survival (RFS) and frequency of adverse events (AEs). RESULTS: Between August 2010 and March 2015, 44 patients (low-dose group: 31 patients and high-dose group: 13 patients) were enrolled in the study. Of these, one patient was excluded from the efficacy analysis. In the high-dose group, five of nine patients were unable to continue the study due to toxicity in February 2013. At that time, recruitment to the high-dose group was stopped from the protocol. The relative dose intensity (RDI) for S-1 in the low- and high-dose groups were 49.8 and 48.7% (p = 0.712), and that for oxaliplatin was 75.9 and 73.0% (p = 0.528), respectively. The rates of discontinuation due to toxicity were 60 and 53.8% in the low- and high-dose groups, respectively, with no marked difference noted between the groups (p = 0.747). The frequency of grade >/= 3 common adverse events was neutropenia (23.3%/23.1%), diarrhea (13.3%/15.4%), and peripheral sensory neuropathy (6.7%/7.7%). The disease-free survival (DFS) at 3 years was 52.9% in the low-dose group, which was not significantly different from that in the high-dose group (46.2%; p = 0.705). CONCLUSIONS: SOX regimens as adjuvant therapy after hepatectomy for CRCLM had high rates of discontinuation due to toxicity in both groups. In particular, the RDI of S-1 was < 50%. Therefore, the SOX regimen is not recommended as adjuvant chemotherapy after hepatectomy for CRCLM. CI - (c) 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. FAU - Ozawa, Mayumi AU - Ozawa M AD - Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan. FAU - Watanabe, Jun AU - Watanabe J AUID- ORCID: 0000-0002-7187-3664 AD - Department of Surgery, Gastroenterological Center, Yokohama City University Medical Center, 4-57, Urafune-cho, Minami-ku, Yokohama, Kanagawa, 232-0024, Japan. nabe-jun@comet.ocn.ne.jp. FAU - Ishibe, Atsushi AU - Ishibe A AD - Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan. FAU - Goto, Koki AU - Goto K AD - Department of Surgery, National Hospital Organization Yokohama Medical Center, Yokohama, Kanagawa, Japan. FAU - Fujii, Yoshiro AU - Fujii Y AD - Department of Surgery, National Hospital Organization Yokohama Medical Center, Yokohama, Kanagawa, Japan. FAU - Nakagawa, Kazuya AU - Nakagawa K AD - Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan. FAU - Suwa, Yusuke AU - Suwa Y AD - Department of Surgery, Gastroenterological Center, Yokohama City University Medical Center, 4-57, Urafune-cho, Minami-ku, Yokohama, Kanagawa, 232-0024, Japan. FAU - Suwa, Hirokazu AU - Suwa H AD - Department of Surgery, Yokosuka Kyosai Hospital, Yokosuka, Kanagawa, Japan. FAU - Masui, Hidenobu AU - Masui H AD - Department of Surgery, Yokosuka Kyosai Hospital, Yokosuka, Kanagawa, Japan. FAU - Sugita, Mitsutaka AU - Sugita M AD - Department of Surgery, Yokohama City Minato Red Cross Hospital, Yokohama, Kanagawa, Japan. FAU - Mochizuki, Yasuhisa AU - Mochizuki Y AD - Department of Gastroenterological Surgery, Yokohama Municipal Citizen's Hospital, Yokohama, Kanagawa, Japan. FAU - Yamagishi, Shigeru AU - Yamagishi S AD - Department of Surgery, Fujisawa City Hospital, Yokohama, Kanagawa, Japan. FAU - Hasegawa, Seiji AU - Hasegawa S AD - Department of Surgery, Saiseikai Yokohamashi Nanbu Hospital, Yokohama, Kanagawa, Japan. FAU - Homma, Yuki AU - Homma Y AD - Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan. FAU - Momiyama, Masashi AU - Momiyama M AD - Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan. FAU - Kumamoto, Takafumi AU - Kumamoto T AD - Department of Surgery, Gastroenterological Center, Yokohama City University Medical Center, 4-57, Urafune-cho, Minami-ku, Yokohama, Kanagawa, 232-0024, Japan. FAU - Matsuyama, Ryusei AU - Matsuyama R AD - Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan. FAU - Takeda, Kazuhisa AU - Takeda K AD - Department of Surgery, Gastroenterological Center, Yokohama City University Medical Center, 4-57, Urafune-cho, Minami-ku, Yokohama, Kanagawa, 232-0024, Japan. FAU - Taguri, Masataka AU - Taguri M AD - Department of Health Data Science, Tokyo Medical University, Tokyo, Japan. FAU - Endo, Itaru AU - Endo I AD - Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan. LA - eng PT - Journal Article DEP - 20240219 PL - Germany TA - Cancer Chemother Pharmacol JT - Cancer chemotherapy and pharmacology JID - 7806519 SB - IM OTO - NOTNLM OT - Adjuvant chemotherapy OT - Colorectal liver metastases OT - Hepatectomy OT - Oxaliplatin OT - S-1 EDAT- 2024/02/20 11:50 MHDA- 2024/02/20 11:50 CRDT- 2024/02/20 00:09 PHST- 2023/10/22 00:00 [received] PHST- 2024/01/29 00:00 [accepted] PHST- 2024/02/20 11:50 [medline] PHST- 2024/02/20 11:50 [pubmed] PHST- 2024/02/20 00:09 [entrez] AID - 10.1007/s00280-024-04648-6 [pii] AID - 10.1007/s00280-024-04648-6 [doi] PST - aheadofprint SO - Cancer Chemother Pharmacol. 2024 Feb 19. doi: 10.1007/s00280-024-04648-6.