{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T07:02:54Z","timestamp":1768287774433,"version":"3.49.0"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T00:00:00Z","timestamp":1766361600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T00:00:00Z","timestamp":1766361600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Pharm Health Care Sci"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Nano-liposomal irinotecan (nal-IRI) combined with 5-fluorouracil (5-FU) and levofolinate has been reported to extend the survival of patients with pancreatic cancer and represents an effective second-line treatment. Nal-IRI encapsulates IRI in liposomes modified with polyethylene glycol (PEGylation), which can lead to infusion reactions. Hypersensitivity reactions (HSR) to chemotherapeutic agents include both allergic and infusion reactions, which are difficult to distinguish. Severe HSR can be fatal; however, discontinuation of the suspected drug directly affects the treatment strategy. We report a case of severe HSR during the first nal-IRI administration, in which treatment was successfully continued with supportive management.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>A woman in her early 80s with metastatic pancreatic cancer received nal-IRI\u2009+\u20095-FU\u2009+\u2009levofolinate as second-line treatment. Five minutes after the initiation of the first nal-IRI infusion, the patient developed a tightening sensation in the head, respiratory distress, convulsions, and loss of consciousness, with percutaneous oxygen saturation dropping to the 80% range. The nal-IRI infusion was immediately discontinued, and emergency management was initiated with intravenous infusion of hydrocortisone, famotidine, d-chlorpheniramine maleate, and oxygen administration, resulting in symptom improvement. Given the limited treatment options for metastatic pancreatic cancer and the patient\u2019s strong desire to continue therapy, we decided to re-administer the regimen with intensified management, increasing dexamethasone to 19.8\u00a0mg and adding famotidine 20\u00a0mg and d-chlorpheniramine maleate 5\u00a0mg. Furthermore, we adopted a three-step dose-escalation method. The infusion was started at one-third of the standard rate, increased to two-thirds after 30\u00a0min, and finally adjusted to the full rate after another 30\u00a0min, after confirming the absence of HSR symptoms. Consequently, the patient did not exhibit any signs of HSR, and the same administration method was continued for 11 cycles until disease progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The novelty of this report lies in presenting, for the first time, the detailed course and process by which treatment was successfully continued in a patient experiencing severe HSR upon initial nal-IRI administration, through enhanced supportive care tailored to the characteristics of the drug and stepwise dose adjustment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40780-025-00514-6","type":"journal-article","created":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T14:25:23Z","timestamp":1766413523000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Successful re-administration after nano-liposomal irinotecan-induced severe hypersensitivity reaction: a case report"],"prefix":"10.1186","volume":"11","author":[{"given":"Ryota","family":"Kanno","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshitaka","family":"Saito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoh","family":"Takekuma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuaki","family":"Harada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshito","family":"Komatsu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitsuru","family":"Sugawara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,12,22]]},"reference":[{"key":"514_CR1","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3322\/caac.21834","volume":"74","author":"F Bray","year":"2024","unstructured":"Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74:229\u201363. https:\/\/doi.org\/10.3322\/caac.21834.","journal-title":"CA Cancer J Clin"},{"key":"514_CR2","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1016\/S0140-6736(15)00986-1","volume":"387","author":"A Wang-Gillam","year":"2016","unstructured":"Wang-Gillam A, Li CP, Bodoky G, Dean A, Shan YS, Jameson G, et al. Nanoliposomal Irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): A global, randomised, open-label, phase 3 trial. Lancet. 2016;387:545\u201357. https:\/\/doi.org\/10.1016\/S0140-6736(15)00986-1.","journal-title":"Lancet"},{"key":"514_CR3","doi-asserted-by":"publisher","first-page":"7003","DOI":"10.1158\/0008-5472.CAN-14-0572","volume":"74","author":"AV Kalra","year":"2014","unstructured":"Kalra AV, Kim J, Klinz SG, Paz N, Cain J, Drummond DC, et al. Preclinical activity of nanoliposomal Irinotecan is governed by tumor deposition and intratumor prodrug conversion. Cancer Res. 2014;74:7003\u201313. https:\/\/doi.org\/10.1158\/0008-5472.CAN-14-0572.","journal-title":"Cancer Res"},{"key":"514_CR4","doi-asserted-by":"publisher","first-page":"1020","DOI":"10.1016\/j.addr.2011.06.017","volume":"63","author":"J Szebeni","year":"2011","unstructured":"Szebeni J, Muggia F, Gabizon A, Barenholz Y. Activation of complement by therapeutic liposomes and other lipid excipient-based therapeutic products: prediction and prevention. Adv Drug Deliv Rev. 2011;63:1020\u201330. https:\/\/doi.org\/10.1016\/j.addr.2011.06.017.","journal-title":"Adv Drug Deliv Rev"},{"key":"514_CR5","doi-asserted-by":"publisher","first-page":"e49","DOI":"10.1016\/j.clcc.2015.05.003","volume":"14","author":"M Abu-Amna","year":"2015","unstructured":"Abu-Amna M, Hassoun G, Hadad S, Haim N, Bar-Sela G. Successful desensitization protocol for hypersensitivity reaction caused by Irinotecan in a patient with metastatic colorectal cancer. Clin Colorectal Cancer. 2015;14:e49\u201351. https:\/\/doi.org\/10.1016\/j.clcc.2015.05.003.","journal-title":"Clin Colorectal Cancer"},{"key":"514_CR6","doi-asserted-by":"publisher","first-page":"314","DOI":"10.18176\/jiaci.0075","volume":"26","author":"JL Cubero","year":"2016","unstructured":"Cubero JL, Escudero P, Yubero A, Mill\u00e1n P, Sagredo MA, Col\u00e1s C. Successful desensitization to Irinotecan after severe hypersensitivity reaction. J Investig Allergol Clin Immunol. 2016;26:314\u20136. https:\/\/doi.org\/10.18176\/jiaci.0075.","journal-title":"J Investig Allergol Clin Immunol"},{"key":"514_CR7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1097\/CAD.0b013e32831961b3","volume":"20","author":"E Syrigou","year":"2009","unstructured":"Syrigou E, Makrilia N, Koti I, Saif MW, Syrigos KN. Hypersensitivity reactions to antineoplastic agents: an overview. Anti Cancer Drugs. 2009;20:1\u20136. https:\/\/doi.org\/10.1097\/CAD.0b013e32831961b3.","journal-title":"Anti Cancer Drugs"},{"issue":"Suppl 4","key":"514_CR8","doi-asserted-by":"publisher","first-page":"iv100","DOI":"10.1093\/annonc\/mdx216","volume":"28","author":"S Rosell\u00f3","year":"2017","unstructured":"Rosell\u00f3 S, Blasco I, Garc\u00eda Fabregat L, Cervantes A, Jordan K. Management of infusion reactions to systemic anticancer therapy: ESMO clinical practice guidelines. Anns Oncol. 2017;28(Suppl 4):iv100\u201318. https:\/\/doi.org\/10.1093\/annonc\/mdx216.","journal-title":"Anns Oncol"},{"key":"514_CR9","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1007\/s10147-024-02535-x","volume":"29","author":"H Iihara","year":"2024","unstructured":"Iihara H, Abe M, Wada M, Iino K, Akechi T, Imamura CK, et al. 2023 Japan society of clinical oncology clinical practice guidelines update for antiemesis. Int J Clin Oncol. 2024;29:873\u201388. https:\/\/doi.org\/10.1007\/s10147-024-02535-x.","journal-title":"Int J Clin Oncol"},{"key":"514_CR10","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1186\/s12885-023-11205-6","volume":"23","author":"R Takada","year":"2023","unstructured":"Takada R, Ikezawa K, Yamai T, Watsuji K, Seiki Y, Kawamoto Y, et al. Parallel administration of nanoliposomal Irinotecan and levo-leucovorin for pancreatic cancer. BMC Cancer. 2023;23:711. https:\/\/doi.org\/10.1186\/s12885-023-11205-6.","journal-title":"BMC Cancer"},{"key":"514_CR11","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1097\/WOX.0b013e318211496c","volume":"4","author":"F Estelle","year":"2011","unstructured":"Estelle F, Simons R, Ardusso LRF, Bil\u00f2 MB, El-Gamal YM, Ledford DK, et al. World allergy organization guidelines for the assessment and management of anaphylaxis. World Allergy Organ J. 2011;4:13\u201337. https:\/\/doi.org\/10.1097\/WOX.0b013e318211496c.","journal-title":"World Allergy Organ J"},{"key":"514_CR12","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1159\/000543992","volume":"18","author":"T Kadono","year":"2025","unstructured":"Kadono T, Kodama H, Yukami H, Yamaguchi T, Nishikawa H. A case of possible infusion-related reactions caused by palonosetron. Case Rep Oncol. 2025;18:353\u201360. https:\/\/doi.org\/10.1159\/000543992.","journal-title":"Case Rep Oncol"},{"key":"514_CR13","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1111\/j.1365-2125.2010.03666.x","volume":"70","author":"YK Gupta","year":"2010","unstructured":"Gupta YK, Shanmugam SP, Padhy BM, Goyal A. Palonosetron induced anaphylaxis in an adult female. Br J Clin Pharmacol. 2010;70:149\u201350. https:\/\/doi.org\/10.1111\/j.1365-2125.2010.03666.x.","journal-title":"Br J Clin Pharmacol"},{"key":"514_CR14","doi-asserted-by":"publisher","first-page":"92","DOI":"10.4168\/aair.2017.9.1.92","volume":"9","author":"H Park","year":"2017","unstructured":"Park H, Oh K, Lee H, Lee JH, Kang SM, Park SY, et al. Palonosetron-induced anaphylaxis during general anesthesia: A case report. Allergy Asthma Immunol Res. 2017;9:92\u20135. https:\/\/doi.org\/10.4168\/aair.2017.9.1.92.","journal-title":"Allergy Asthma Immunol Res"},{"key":"514_CR15","doi-asserted-by":"publisher","first-page":"654","DOI":"10.3390\/cimb47080654","volume":"47","author":"K Lis","year":"2025","unstructured":"Lis K. Hypersensitivity to folic acid and\/or folinic acid- A review of clinical cases, potential mechanism, possible cross-allergies and current diagnostic options. Curr Issues Mol Biol. 2025;47:654. https:\/\/doi.org\/10.3390\/cimb47080654.","journal-title":"Curr Issues Mol Biol"},{"key":"514_CR16","doi-asserted-by":"publisher","first-page":"7174","DOI":"10.1002\/cam4.4252","volume":"10","author":"N Horita","year":"2021","unstructured":"Horita N, Miyagi E, Mizushima T, Hagihara M, Hata C, Hattori Y, et al. Severe anaphylaxis caused by intravenous anti-cancer drugs. Cancer Med. 2021;10:7174\u201383. https:\/\/doi.org\/10.1002\/cam4.4252.","journal-title":"Cancer Med"},{"key":"514_CR17","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1016\/j.tox.2005.07.023","volume":"216","author":"J Szebeni","year":"2005","unstructured":"Szebeni J. Complement activation-related pseudoallergy: A new class of drug-induced acute immune toxicity. Toxicology. 2005;216:106\u201321. https:\/\/doi.org\/10.1016\/j.tox.2005.07.023.","journal-title":"Toxicology"},{"key":"514_CR18","doi-asserted-by":"publisher","first-page":"1563","DOI":"10.2147\/IJN.s187139","volume":"14","author":"E \u0150rfi","year":"2019","unstructured":"\u0150rfi E, M\u00e9sz\u00e1ros T, Hennies M, F\u00fcl\u00f6p T, D\u00e9zsi L, Nardocci A, et al. Acute physiological changes caused by complement activators and amphotericin B-containing liposomes in mice. Int J Nanomed. 2019;14:1563\u201373. https:\/\/doi.org\/10.2147\/IJN.s187139.","journal-title":"Int J Nanomed"},{"key":"514_CR19","doi-asserted-by":"publisher","first-page":"21","DOI":"10.3816\/CLM.2008.n.001","volume":"8","author":"R Solomon","year":"2008","unstructured":"Solomon R, Gabizon AA. Clinical Pharmacology of liposomal anthracyclines: focus on pegylated liposomal doxorubicin. Clin Lymphoma Myeloma. 2008;8:21\u201332.","journal-title":"Clin Lymphoma Myeloma"},{"key":"514_CR20","doi-asserted-by":"publisher","first-page":"3886","DOI":"10.3390\/ijms24043886","volume":"24","author":"B Galateanu","year":"2023","unstructured":"Galateanu B, Pu\u0219ca\u0219u AI, Tircol SA, Tanase BC, Hudita A, Negrei C, et al. Allergy in cancer care: antineoplastic therapy-induced hypersensitivity reactions. Int J Mol Sci. 2023;24:3886. https:\/\/doi.org\/10.3390\/ijms24043886.","journal-title":"Int J Mol Sci"},{"key":"514_CR21","doi-asserted-by":"publisher","first-page":"7824","DOI":"10.3390\/jcm13247824","volume":"13","author":"S Ali","year":"2024","unstructured":"Ali S, Nedelcu DM, Serescu R, Bumb\u0103cea RS. Successful desensitization to Irinotecan in a patient with metastatic esophageal squamous cell carcinoma and a history of anaphylaxis in response to Irinotecan-case report and literature review. J Clin Med. 2024;13:7824. https:\/\/doi.org\/10.3390\/jcm13247824.","journal-title":"J Clin Med"},{"key":"514_CR22","doi-asserted-by":"publisher","first-page":"573573","DOI":"10.3389\/fphar.2020.573573","volume":"11","author":"A Copaescu","year":"2021","unstructured":"Copaescu A, Gibson A, Li Y, Trubiano JA, Phillips EJ. An updated review of the diagnostic methods in delayed drug hypersensitivity. Front Pharmacol. 2021;11:573573. https:\/\/doi.org\/10.3389\/fphar.2020.573573.","journal-title":"Front Pharmacol"},{"key":"514_CR23","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1016\/j.jaci.2013.07.046","volume":"132","author":"MC Siracusa","year":"2013","unstructured":"Siracusa MC, Kim BS, Spergel JM, Artis D. Basophils and allergic inflammation. J Allergy Clin Immunol. 2013;132:789\u2013801. https:\/\/doi.org\/10.1016\/j.jaci.2013.07.046.","journal-title":"J Allergy Clin Immunol"},{"key":"514_CR24","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1016\/j.annonc.2023.08.009","volume":"34","author":"T Conroy","year":"2023","unstructured":"Conroy T, Pfeiffer P, Vilgrain V, Lamarca A, Seufferlein T, O\u2019Reilly EM, et al. Pancreatic cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol. 2023;34:987\u20131002. https:\/\/doi.org\/10.1016\/j.annonc.2023.08.009.","journal-title":"Ann Oncol"}],"container-title":["Journal of Pharmaceutical Health Care and Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40780-025-00514-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40780-025-00514-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40780-025-00514-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T03:02:50Z","timestamp":1766458970000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s40780-025-00514-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,22]]},"references-count":24,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["514"],"URL":"https:\/\/doi.org\/10.1186\/s40780-025-00514-6","relation":{},"ISSN":["2055-0294"],"issn-type":[{"value":"2055-0294","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,22]]},"assertion":[{"value":"4 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 November 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 December 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was conducted in compliance with the Declaration of Helsinki. Written informed consent was obtained from the patient to publish the details of the medical case. Case reports were exempted from ethics approval at the Hokkaido University Hospital.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Written informed consent was obtained from the patient.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"110"}}