{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T06:10:14Z","timestamp":1792044614127,"version":"4.4.0"},"reference-count":32,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,15]],"date-time":"2025-06-15T00:00:00Z","timestamp":1749945600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Zolbetuximab, a monoclonal antibody targeting claudin-18.2 (CLDN18.2), which was recently approved as first-line treatment for advanced gastric cancer (AGC), presents unique safety challenges, particularly infusion-related gastrointestinal toxicity and hypoalbuminemia. This study aimed to present our experience with zolbetuximab administration in patients with AGC, focusing on the safety and management effectiveness of our adapted protocol in routine clinical practice. Methods: This study presents our single-institution real-world experience implementing a proactive management protocol (\u201cProject VYLOY\u201d) using zolbetuximab to mitigate these toxicities. We adopted a standardized stepwise infusion protocol and antiemetic premedication to reduce infusion-related nausea and vomiting. Patients with CLDN18.2-positive advanced gastric or gastroesophageal junction adenocarcinoma who received zolbetuximab combined with chemotherapy were included. Results: Twenty-four patients were included. The median infusion duration was 215 min, with an interruption rate of 25.0%. In cycle 1, 62.5% experienced infusion-associated adverse events, primarily grade 1 nausea (54%) and vomiting (25%). Hypoalbuminemia (grade \u2265 2) occurred in 57% of first-line patients, potentially linked to zolbetuximab-induced gastritis and gastrointestinal protein loss. Proactive antiemetic support and infusion rate adjustments substantially reduced infusion interruptions in subsequent cycles (10.9%). Patients without prior gastrectomy had higher nausea and vomiting rates, confirming the stomach\u2019s role in mediating toxicity. Conclusions: Our results suggest that proactive management can improve the safety and tolerability of zolbetuximab, especially by reducing infusion-related toxicity in real-world practice.<\/jats:p>","DOI":"10.3390\/cancers17121996","type":"journal-article","created":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T04:06:24Z","timestamp":1750046784000},"page":"1996","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Practical Management of Zolbetuximab Administration: The Project VYLOY Initiative"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8018-0077","authenticated-orcid":false,"given":"Yukiya","family":"Narita","sequence":"first","affiliation":[{"name":"Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya 464-8681, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8170-3054","authenticated-orcid":false,"given":"Taro","family":"Mizuno","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya 464-8681, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takato","family":"Suda","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Aichi Cancer Center Hospital, Nagoya 464-8681, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junko","family":"Kurono","sequence":"additional","affiliation":[{"name":"Department of Nursing, Aichi Cancer Center Hospital, Nagoya 464-8681, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasunobu","family":"Ishizuka","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya 464-8681, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumi","family":"Iida","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Aichi Cancer Center Hospital, Nagoya 464-8681, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Kondo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Aichi Cancer Center Hospital, Nagoya 464-8681, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2093-3695","authenticated-orcid":false,"given":"Kazuhiro","family":"Shimomura","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Aichi Cancer Center Hospital, Nagoya 464-8681, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chisato","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Nursing, Aichi Cancer Center Hospital, Nagoya 464-8681, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eri","family":"Hotta","sequence":"additional","affiliation":[{"name":"Department of Nursing, Aichi Cancer Center Hospital, Nagoya 464-8681, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Kuraishi","sequence":"additional","affiliation":[{"name":"Department of Nursing, Aichi Cancer Center Hospital, Nagoya 464-8681, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanae","family":"Tozaki","sequence":"additional","affiliation":[{"name":"Medical Safety Management Office, Aichi Cancer Center Hospital, Nagoya 464-8681, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makiko","family":"Kobara","sequence":"additional","affiliation":[{"name":"Clinical Trial Department, Aichi Cancer Center Hospital, Nagoya 464-8681, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chihoko","family":"Takahata","sequence":"additional","affiliation":[{"name":"Department of Nursing, Aichi Cancer Center Hospital, Nagoya 464-8681, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5572-743X","authenticated-orcid":false,"given":"Kei","family":"Muro","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya 464-8681, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"229","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA A Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1002\/1097-0142(19930701)72:1<37::AID-CNCR2820720109>3.0.CO;2-P","article-title":"Modified therapy with 5-fluorouracil, doxorubicin, and methotrexate in advanced gastric cancer","volume":"72","author":"Murad","year":"1993","journal-title":"Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/S0140-6736(10)61121-X","article-title":"Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): A phase 3, open-label, randomised controlled trial","volume":"376","author":"Bang","year":"2010","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1001\/jamaoncol.2020.3370","article-title":"Efficacy and Safety of Pembrolizumab or Pembrolizumab Plus Chemotherapy vs Chemotherapy Alone for Patients With First-line, Advanced Gastric Cancer: The KEYNOTE-062 Phase 3 Randomized Clinical Trial","volume":"6","author":"Shitara","year":"2020","journal-title":"JAMA Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S0140-6736(21)00797-2","article-title":"First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): A randomised, open-label, phase 3 trial","volume":"398","author":"Janjigian","year":"2021","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1038\/s41586-022-04508-4","article-title":"Nivolumab plus chemotherapy or ipilimumab in gastro-oesophageal cancer","volume":"603","author":"Shitara","year":"2022","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1016\/S0140-6736(23)00620-7","article-title":"Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): A multicentre, randomised, double-blind, phase 3 trial","volume":"401","author":"Shitara","year":"2023","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.1038\/s41591-023-02465-7","article-title":"Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: The randomized, phase 3 GLOW trial","volume":"29","author":"Shah","year":"2023","journal-title":"Nat. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"100762","DOI":"10.1016\/j.esmoop.2022.100762","article-title":"Comprehensive clinical and molecular characterization of claudin 18.2 expression in advanced gastric or gastroesophageal junction cancer","volume":"8","author":"Kubota","year":"2023","journal-title":"ESMO Open"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1038\/s41571-024-00874-2","article-title":"Claudin 18.2 as a novel therapeutic target","volume":"21","author":"Nakayama","year":"2024","journal-title":"Nat Rev Clin Oncol"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Jia, K., Chen, Y., Sun, Y., Hu, Y., Jiao, L., Ma, J., Yuan, J., Qi, C., Li, Y., and Gong, J. (2022). Multiplex immunohistochemistry defines the tumor immune microenvironment and immunotherapeutic outcome in CLDN18.2-positive gastric cancer. BMC Med., 20.","DOI":"10.1186\/s12916-022-02421-1"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/j.annonc.2021.02.005","article-title":"FAST: A randomised phase II study of zolbetuximab (IMAB362) plus EOX versus EOX alone for first-line treatment of advanced CLDN18.2-positive gastric and gastro-oesophageal adenocarcinoma","volume":"32","author":"Sahin","year":"2021","journal-title":"Ann. Oncol. Off. J. Eur. Soc. Med. Oncol. ESMO"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Angerilli, V., Callegarin, M., Govoni, I., De Lisi, G., Paudice, M., Fugazzola, P., Vanoli, A., Parente, P., Bergamo, F., and Luchini, C. (2025). Heterogeneity of predictive biomarker expression in gastric and esophago-gastric junction carcinoma with peritoneal dissemination. Gastric Cancer Off. J. Int. Gastric Cancer Assoc. Jpn. Gastric Cancer Assoc., 1\u201310.","DOI":"10.1007\/s10120-025-01609-7"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"100128","DOI":"10.1016\/j.esmogo.2024.100128","article-title":"Managing zolbetuximab-induced nausea and vomiting: A proposal for a pragmatic approach in clinical practice","volume":"7","author":"Shimozaki","year":"2025","journal-title":"ESMO Gastrointest. Oncol."},{"key":"ref_15","first-page":"403","article-title":"Final overall survival results from phase 3 SPOTLIGHT study evaluating zolbetuximab + mFOLFOX6 as first-line (1L) treatment for patients (pts) with claudin 18 isoform 2 (CLDN18.2)+, HER2\u2212, locally advanced (LA) unresectable or metastatic gastric or gastroesophageal junction (mG\/GEJ) adenocarcinoma","volume":"42","author":"Shitara","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"100131","DOI":"10.1016\/j.esmogo.2024.100131","article-title":"Consensus guidance for prevention and management of nausea and vomiting in patients treated with zolbetuximab + chemotherapy: A RAND\/UCLA modified Delphi panel study","volume":"7","author":"Klempner","year":"2025","journal-title":"ESMO Gastrointest. Oncol."},{"key":"ref_17","unstructured":"Yamada, C., Narita, Y., and Suda, T. (2025, January 6\u20138). Multidisciplinary Collaboration in the Clinical Implementation of Zolbetuximab Leveraging the Clinical Path. Proceedings of the 22nd Annual Meeting of Japanese Society of Medical Oncology., Kobe, Japan."},{"key":"ref_18","unstructured":"Suda, T., Narita, Y., and Yamada, C. (2025, January 12\u201314). Importance of Multidisciplinary Collaboration and Information Sharing in the Clinical Implementation of Zolbetuximab. Proceedings of the 97th Annual Meeting of the Japanese Gastric Cancer Association, Nagoya, Japan."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"17588359231217967","DOI":"10.1177\/17588359231217967","article-title":"Zolbetuximab for Claudin18.2-positive gastric or gastroesophageal junction cancer","volume":"16","author":"Kubota","year":"2024","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1093\/jjco\/hyz068","article-title":"Comparison of Claudin 18.2 expression in primary tumors and lymph node metastases in Japanese patients with gastric adenocarcinoma","volume":"49","author":"Rohde","year":"2019","journal-title":"Jpn. J. Clin. Oncol."},{"key":"ref_21","unstructured":"Institute, N.C. (2025, April 02). Common Terminology Criteria for Adverse Events (CTCAE) v5.0, Available online: https:\/\/ctep.cancer.gov\/protocoldevelopment\/electronic_applications\/ctc.htm."},{"key":"ref_22","first-page":"280","article-title":"2020 ASCO, 2023 NCCN, 2023 MASCC\/ESMO, and 2019 CCO: A comparison of antiemetic guidelines for the treatment of chemotherapy-induced nausea and vomiting in cancer patients","volume":"32","author":"Kennedy","year":"2024","journal-title":"Support. Care Cancer Off. J. Multinatl. Assoc. Support. Care Cancer"},{"key":"ref_23","first-page":"87","article-title":"ASCO, NCCN, MASCC\/ESMO: A comparison of antiemetic guidelines for the treatment of chemotherapy-induced nausea and vomiting in adult patients","volume":"27","author":"Razvi","year":"2019","journal-title":"Support. Care Cancer Off. J. Multinatl. Assoc. Support. Care Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"102195","DOI":"10.1016\/j.esmoop.2023.102195","article-title":"2023 MASCC and ESMO guideline update for the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting","volume":"9","author":"Herrstedt","year":"2024","journal-title":"ESMO Open"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1007\/s10147-024-02536-w","article-title":"Non-pharmacological treatments for anticipatory nausea and vomiting during chemotherapy: A systematic review and meta-analysis of the Clinical Practice Guidelines for Antiemesis 2023","volume":"29","author":"Kobayashi","year":"2024","journal-title":"Int. J. Clin. Oncol. Jpn. Soc. Clin. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s10147-024-02663-4","article-title":"Clinical benefits of adding olanzapine to 5-HT(3) receptor antagonist, NK(1) receptor antagonist, and dexamethasone for the prevention of nausea and vomiting in highly emetogenic chemotherapy: A systematic review and meta-analysis of the Clinical Practice Guidelines for Antiemesis 2023 from the Japan Society of Clinical Oncology","volume":"30","author":"Murakami","year":"2025","journal-title":"Int. J. Clin. Oncol. Jpn. Soc. Clin. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1007\/s10147-024-02643-8","article-title":"Efficacy and safety of dexamethasone sparing for the prevention of nausea and vomiting associated with moderately emetogenic chemotherapy: A systematic review and meta-analysis of Clinical Practice Guidelines for Antiemesis 2023 from Japan Society of Clinical Oncology","volume":"29","author":"Nakashima","year":"2024","journal-title":"Int. J. Clin. Oncol. Jpn. Soc. Clin. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.ejca.2008.10.026","article-title":"New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1)","volume":"45","author":"Eisenhauer","year":"2009","journal-title":"Eur. J. Cancer"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.jphs.2024.08.005","article-title":"Effect of antiemetics on zolbetuximab-induced gastric injury and emesis in ferrets","volume":"156","author":"Kinugasa","year":"2024","journal-title":"J. Pharmacol. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Sugiyama, Y., Tanabe, H., Tachibana, S., Iribe, K., Yuzawa, S., Iwaki, H., Yoshida, Y., and Fujiya, M. (2025). Zolbetuximab-related gastritis: A case report of the patient with prolonged gastrointestinal symptoms. Gastric Cancer Off. J. Int. Gastric Cancer Assoc. Jpn. Gastric Cancer Assoc., 1\u20137.","DOI":"10.1007\/s10120-025-01607-9"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Yanagimoto, Y., Yamamoto, K., Hara, K., Masuike, Y., Ushimaru, Y., Kitamura, M., Honma, K., Matsuura, N., Sugase, T., and Kanemura, T. (2025). Two cases of protein-losing enteropathy induced by zolbetuximab in patients with unresectable advanced gastric cancer. Jpn. J. Clin. Oncol., hyaf055.","DOI":"10.1093\/jjco\/hyaf055"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1200\/JCO.21.02810","article-title":"The Time Toxicity of Cancer Treatment","volume":"40","author":"Gupta","year":"2022","journal-title":"J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/12\/1996\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:52:24Z","timestamp":1760032344000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/12\/1996"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,15]]},"references-count":32,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["cancers17121996"],"URL":"https:\/\/doi.org\/10.3390\/cancers17121996","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,15]]}}}