PMID- 35999529 OWN - NLM STAT- MEDLINE DCOM- 20220825 LR - 20220827 IS - 1471-2407 (Electronic) IS - 1471-2407 (Linking) VI - 22 IP - 1 DP - 2022 Aug 23 TI - The change rate in serum nitric oxide may affect lenvatinib therapy in hepatocellular carcinoma. PG - 912 LID - 10.1186/s12885-022-10002-x [doi] LID - 912 AB - BACKGROUND: Lenvatinib is appropriate for reducing the production of nitric oxide (NO) and facilitating as block angiogenesis. However, to our knowledge, there are no data that support the correlation between NO and clinical response in patients who received lenvatinib therapy for HCC. Therefore, we investigated the correlation between the change rate of NO levels and clinical responses including adverse events (AEs) after lenvatinib therapy for unresectable hepatocellular carcinoma (HCC). METHODS: This study was conducted using previously collected data from another study. We enrolled 70 patients who received lenvatinib for advanced or unresectable HCC. NO was measured by converting nitrate (NO(3)(-)) to nitrite (NO(2)(-)) with nitrate reductase, followed by quantitation of NO(2)(-) based on Griess reagent. To determine whether lenvatinib influences NO in unresectable HCC, we evaluated the influence of the change rate of NO from baseline after administration of lenvatinib on maximal therapeutic response and SAE. RESULTS: After lenvatinib administration, a change rate in the NO from 0.27 to 4.16 was observed. There was no difference between the clinical response to lenvatinib and the change rate of NO (p = 0.632). However, the change rate of NO was significantly lower in patients with AEs than in those without AEs (p = 0.030). When a reduction in NO rate of < 0.8 was defined as a clinically significant reduction of NO (CSRN), the CSRN group had significantly worse progression-free survival (PFS) and overall survival (OS) than the non-CSRN group (p = 0.029 and p = 0.005, respectively). CONCLUSION: Decreased NO levels were associated with the occurrence of AEs and worse prognosis after lenvatinib administration. Change rate in serum NO can be used as predictive markers in patients receiving lenvatinib therapy for HCC. CI - (c) 2022. The Author(s). FAU - Kawamura, Atsushi AU - Kawamura A AD - Department of Pharmacy, Kitasato University Hospital, Sagamihara, Kanagawa, Japan. FAU - Uojima, Haruki AU - Uojima H AD - Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0375, Japan. kiruha@kitasato-u.ac.jp. AD - Gastroenterology Medicine Center, Shonan Kamakura General Hospital, Kamakura, Kanagawa, Japan. kiruha@kitasato-u.ac.jp. FAU - Chuma, Makoto AU - Chuma M AD - Department of Gastroenterology, Yokohama City University Hospital, Yokohama, Kanagawa, Japan. AD - Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Kanagawa, Japan. FAU - Shao, Xue AU - Shao X AD - Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0375, Japan. FAU - Hidaka, Hisashi AU - Hidaka H AD - Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0375, Japan. FAU - Nakazawa, Takahide AU - Nakazawa T AD - Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0375, Japan. AD - Nakazawa Internal Medicine Clinic, Sagamihara, Kanagawa, Japan. FAU - Take, Akira AU - Take A AD - Department of Microbiology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan. FAU - Sakaguchi, Yoshihiko AU - Sakaguchi Y AD - Department of Microbiology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan. FAU - Numata, Kazushi AU - Numata K AD - Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Kanagawa, Japan. FAU - Kako, Makoto AU - Kako M AD - Gastroenterology Medicine Center, Shonan Kamakura General Hospital, Kamakura, Kanagawa, Japan. FAU - Nozaki, Akito AU - Nozaki A AD - Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Kanagawa, Japan. FAU - Azuma, Shintaro AU - Azuma S AD - Department of Pharmacy, Kitasato University Hospital, Sagamihara, Kanagawa, Japan. FAU - Horio, Kazue AU - Horio K AD - Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0375, Japan. FAU - Kusano, Chika AU - Kusano C AD - Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0375, Japan. FAU - Atsuda, Koichiro AU - Atsuda K AD - Department of Pharmacy, Kitasato University Hospital, Sagamihara, Kanagawa, Japan. AD - School of Pharmaceutical Sciences, Kitasato University, Shirokane, Minato-ku, Tokyo, Japan. LA - eng PT - Journal Article DEP - 20220823 PL - England TA - BMC Cancer JT - BMC cancer JID - 100967800 RN - 0 (Antineoplastic Agents) RN - 0 (Phenylurea Compounds) RN - 0 (Quinolines) RN - 31C4KY9ESH (Nitric Oxide) RN - EE083865G2 (lenvatinib) RN - S7G510RUBH (Nitrogen Dioxide) SB - IM MH - *Antineoplastic Agents/adverse effects MH - *Carcinoma, Hepatocellular/pathology MH - Humans MH - *Liver Neoplasms/pathology MH - Nitric Oxide MH - Nitrogen Dioxide/therapeutic use MH - Phenylurea Compounds/adverse effects MH - *Quinolines/adverse effects PMC - PMC9396897 OTO - NOTNLM OT - Adverse effects OT - Hepatocellular carcinoma OT - Lenvatinib therapy OT - Nitric oxide OT - Overall survival OT - Progression-free survival COIS- The authors declare that they have no competing interests as defined by Nature Research, or other interests that might be perceived to influence the results and/or discussion reported in this paper. EDAT- 2022/08/24 06:00 MHDA- 2022/08/26 06:00 PMCR- 2022/08/23 CRDT- 2022/08/23 23:34 PHST- 2022/02/28 00:00 [received] PHST- 2022/08/05 00:00 [accepted] PHST- 2022/08/23 23:34 [entrez] PHST- 2022/08/24 06:00 [pubmed] PHST- 2022/08/26 06:00 [medline] PHST- 2022/08/23 00:00 [pmc-release] AID - 10.1186/s12885-022-10002-x [pii] AID - 10002 [pii] AID - 10.1186/s12885-022-10002-x [doi] PST - epublish SO - BMC Cancer. 2022 Aug 23;22(1):912. doi: 10.1186/s12885-022-10002-x.