Misdiagnosis of severe and atypical oxaliplatin‑related hypersensitivity reaction following chemotherapy combined with PD‑1 inhibitor: A case report and literature review

Sun,Maoben; Xu,Guihua; Cai,Liangzhen; He,Shaozhong

doi:10.3892/ol.2024.14586

Misdiagnosis of severe and atypical oxaliplatin‑related hypersensitivity reaction following chemotherapy combined with PD‑1 inhibitor: A case report and literature review

Authors:
- Maoben Sun
- Guihua Xu
- Liangzhen Cai
- Shaozhong He
View Affiliations

Affiliations: Department of Oncology, Binhaiwan Central Hospital of Dongguan, Dongguan, Guangdong 523000, P.R. China, Dongguan Key Laboratory of Precision Medicine, Binhaiwan Central Hospital of Dongguan, Dongguan, Guangdong 523000, P.R. China
Published online on: July 23, 2024 https://doi.org/10.3892/ol.2024.14586
Article Number: 452
Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Although the efficacy of treatment strategies for cancer have been improving steadily over the past decade, the adverse event profile following such treatments has also become increasingly complex. The present report described the case of a 67‑year‑old male patient with gastric stump carcinoma with liver invasion. The patient was treated with oxaliplatin and capecitabine (CAPEOX regimen) chemotherapy, combined with the programmed cell death protein‑1 (PD‑1) inhibitor tislelizumab. Following treatment, the patient suffered from chills, high fever and facial flushing, followed by shock. Relevant examination results revealed severe multiple organ damage, as well as a significant elevation in IL‑6 and procalcitonin (PCT) levels. Initially, the patient was diagnosed with either immune‑related adverse events (irAEs) associated with cytokine release syndrome caused by tislelizumab or severe bacterial infection. However, when tislelizumab treatment was stopped and the CAPEOX chemotherapy regimen was reapplied, similar symptoms recurred. Following screening, it was finally determined that severe hypersensitivity reaction (HSR) caused by oxaliplatin was the cause underlying these symptoms. A literature review was then performed, which found that severe oxaliplatin‑related HSR is rare, rendering the present case atypical. The present case exhibited no common HSR symptoms, such as cutaneous and respiratory symptoms. However, the patient suffered from serious multiple organ damage, which was misdiagnosed as irAE when oxaliplatin chemotherapy combined with the PD‑1 inhibitor was administered. In addition, this apparent severe oxaliplatin‑related HSR caused a significant increase in PCT levels, which was misdiagnosed as severe bacterial infection and prevented the use of glucocorticoids. This, in turn, aggravated the damage in this patient.

View Figures

View References

1	Lustberg MB, Kuderer NM, Desai A, Bergerot C and Lyman GH: Mitigating long-term and delayed adverse events associated with cancer treatment: Implications for survivorship. Nat Rev Clin Oncol. 20:527–542. 2023. View Article : Google Scholar : PubMed/NCBI
2	Kuderer NM, Desai A, Lustberg MB and Lyman GH: Mitigating acute chemotherapy-associated adverse events in patients with cancer. Nat Rev Clin Oncol. 19:681–697. 2022. View Article : Google Scholar : PubMed/NCBI
3	Gowda A, Goel R, Berdzik J, Leichman CG and Javle M: Hypersensitivity reactions to oxaliplatin: Incidence and management. Oncology (Williston Park). 18:1671–1675. 167616801683–1684. 2004.PubMed/NCBI
4	Terashima M, Kang YK, Kim YW, Boku N, Chung HCC, Chen JS, Ji J, Yeh TS, ChenL T, Ryu MH, et al: ATTRACTION-5: A phase 3 study of nivolumab plus chemotherapy as postoperative adjuvant treatment for pathological stage III (pStage III) gastric or gastroesophageal junction (G/GEJ) cancer. J Clin Oncol. 41 (Suppl 16):S40002023. View Article : Google Scholar
5	Stahl M, Köster W and Wilke H: Reaction after oxaliplatin-prevention with corticosteroids? Ann Oncol. 12:8742001. View Article : Google Scholar : PubMed/NCBI
6	Santini D, Tonini G, Salerno A, Vincenzi B, Patti G, Battistoni F, Dicuonzo G and Labianca R: Idiosyncratic reaction after oxaliplatin infusion. Ann Oncol. 12:132–133. 2001. View Article : Google Scholar : PubMed/NCBI
7	Brandi G, Pantaleo MA, Galli C, Falcone A, Antonuzzo A, Mordenti P, Di Marco MC and Biasco G: Hypersensitivity reactions related to oxaliplatin (OHP). Br J Cancer. 89:477–481. 2003. View Article : Google Scholar : PubMed/NCBI
8	André T, Boni C, Mounedji-Boudiaf L, Navarro M, Tabernero J, Hickish T, Topham C, Zaninelli M, Clingan P, Bridgewater J, et al: Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med. 350:2343–2351. 2004. View Article : Google Scholar : PubMed/NCBI
9	Siu SWK, Chan RTT and Au GKH: Hypersensitivity reactions to oxaliplatin: Experience in a single institute. Ann Oncol. 17:259–261. 2006. View Article : Google Scholar : PubMed/NCBI
10	Shao YY, Hu FC, Liang JT, Chiu WT, Cheng AL and Yang CH: Characteristics and risk factors of oxaliplatin-related hypersensitivity reactions. J Formos Med Assoc. 109:362–368. 2010. View Article : Google Scholar : PubMed/NCBI
11	Parel M, Ranchon F, Nosbaum A, You B, Vantard N, Schwiertz V, Gourc C, Gauthier N, Guedat MG, He S, et al: Hypersensitivity to oxaliplatin: Clinical features and risk factors. BMC Pharmacol Toxicol. 15:12014. View Article : Google Scholar : PubMed/NCBI
12	Okayama T, Ishikawa T, Sugatani K, Yoshida N, Kokura S, Matsuda K, Tsukamoto S, Ihara N, Kuriu Y, Nakanishi M, et al: Hypersensitivity reactions to oxaliplatin: Identifying the risk factors and judging the efficacy of a desensitization protocol. Clin Ther. 37:1259–1269. 2015. View Article : Google Scholar : PubMed/NCBI
13	Shen Y, Li C, Liu W, Mao W, Qian H, Wang H and Xu Q: Clinical analysis of hypersensitivity reactions to oxaliplatin among colorectal cancer patients. Oncol Res. 26:801–807. 2018. View Article : Google Scholar : PubMed/NCBI
14	Sohn KH, Kang DY, Kim JY, Lee SY, Lee KH, Han SW and Kang HR: Incidence and risk of oxaliplatin-induced hypersensitivity in patients with asymptomatic prior exposure: A prospective observational study. J Allergy Clin Immunol Pract. 6:1642–1648.e2. 2018. View Article : Google Scholar : PubMed/NCBI
15	Barbin F, Ghidini M, Panichi A, Tomasello G, Bareggi C, Galassi B, Denaro N, Ruatta F, Cauchi C, Rossino MG and Garrone O: Oxaliplatin-related hypersensitivity reactions: A single institution series and literature review. Biomedicines. 10:32752022. View Article : Google Scholar : PubMed/NCBI
16	Selcuk A and Yıldız B: Oxaliplatin-induced hypersensitivity reactions: Risk factors and management. Eur Rev Med Pharmacol Sci. 27:2640–2645. 2023.PubMed/NCBI
17	Puzanov I, Diab A, Abdallah K, Bingham CO III, Brogdon C, Dadu R, Hamad L, Kim S, Lacouture ME, LeBoeuf NR, et al: Managing toxicities associated with immune checkpoint inhibitors: Consensus recommendations from the Society for Immunotherapy of Cancer (SITC) toxicity management working group. J Immunother Cancer. 5:952017. View Article : Google Scholar : PubMed/NCBI
18	Lee DW, Gardner R, Porter DL, Louis CU, Ahmed N, Jensen M, Grupp SA and Mackall CL: Current concepts in the diagnosis and management of cytokine release syndrome. Blood. 124:188–195. 2014. View Article : Google Scholar : PubMed/NCBI
19	Fajgenbaum DC and June CH: Cytokine storm. N Engl J Med. 383:2255–2273. 2020. View Article : Google Scholar : PubMed/NCBI
20	Rotz SJ, Leino D, Szabo S, Mangino JL, Turpin BK and Pressey JG: Severe cytokine release syndrome in a patient receiving PD-1-directed therapy. Pediatr Blood Cancer. 64:e266422017. View Article : Google Scholar : PubMed/NCBI
21	Polyzos A, Tsavaris N, Gogas H, Souglakos J, Vambakas L, Vardakas N, Polyzos K, Tsigris C, Mantas D, Papachristodoulou A, et al: Clinical features of hypersensitivity reactions to oxaliplatin: A 10-year experience. Oncology. 76:36–41. 2009. View Article : Google Scholar : PubMed/NCBI
22	Mahmood SS, Fradley MG, Cohen JV, Nohria A, Reynolds KL, Heinzerling LM, Sullivan RJ, Damrongwatanasuk R, Chen CL, Gupta D, et al: Myocarditis in patients treated with immune checkpoint inhibitors. J Am Coll Cardiol. 71:1755–1764. 2018. View Article : Google Scholar : PubMed/NCBI
23	Wang DY, Salem JE, Cohen JV, Chandra S, Menzer C, Ye F, Zhao S, Das S, Beckermann KE, Ha L, et al: Fatal toxic effects associated with immune checkpoint inhibitors: A systematic review and meta-analysis. JAMA Oncol. 4:1721–1728. 2018. View Article : Google Scholar : PubMed/NCBI
24	Neeser O, Branche A, Mueller B and Schuetz P: How to: Implement procalcitonin testing in my practice. Clin Microbiol Infect. 25:1226–1230. 2019. View Article : Google Scholar : PubMed/NCBI
25	Oh DY, Cham J, Zhang L, Fong G, Kwek SS, Klinger M, Faham M and Fong L: Immune toxicities elicted by CTLA-4 blockade in cancer patients are associated with early diversification of the T-cell repertoire. Cancer Res. 77:1322–1330. 2017. View Article : Google Scholar : PubMed/NCBI
26	Diehl A, Yarchoan M, Hopkins A, Jaffee E and Grossman SA: Relationships between lymphocyte counts and treatment-related toxicities and clinical responses in patients with solid tumors treated with PD-1 checkpoint inhibitors. Oncotarget. 8:114268–114280. 2017. View Article : Google Scholar : PubMed/NCBI
27	Subudhi SK, Aparicio A, Gao J, Zurita AJ, Araujo JC, Logothetis CJ, Tahir SA, Korivi BR, Slack RS, Vence L, et al: Clonal expansion of CD8 T cells in the systemic circulation precedes development of ipilimumab-induced toxicities. Proc Natl Acad Sci USA. 113:11919–11924. 2016. View Article : Google Scholar : PubMed/NCBI
28	Yu Y, Wang S, Su N, Pan S, Tu B, Zhao J, Shen Y, Qiu Q, Liu X, Luan J, et al: Increased circulating levels of CRP and IL-6 and decreased frequencies of T and B lymphocyte subsets are associated with immune-related adverse events during combination therapy with PD-1 inhibitors for liver cancer. Front Oncol. 12:9068242022. View Article : Google Scholar : PubMed/NCBI
29	Melero I, Berman DM, Aznar MA, Korman AJ, Pérez Gracia JL and Haanen J: Evolving synergistic combinations of targeted immunotherapies to combat cancer. Nat Rev Cancer. 15:457–472. 2015. View Article : Google Scholar : PubMed/NCBI