D1.378 - Hypersensitivity During Continuous 5-Fluorouracil Infusion: Two Cases Successfully Managed With Desensitization

introduction: Fluorouracil (5-FU) is a pyrimidine analogue widely used in gastrointestinal malignancies.Hypersensitivity reactions (HSRs) to antineoplastic agents are most frequently reported with platinum compounds, taxanes, L-asparaginase, and epipodophyllotoxins, whereas antimetabolites such as 5-FU are rarely implicated.Nevertheless, flushing, angioedema, and anaphylaxis during 5-FU infusion have been sporadically reported.In cases where 5-FU is clinically indispensable, desensitization represents a valuable strategy to ensure treatment continuity.Here, we present two cases of successful 5-FU desensitization following infusion-related hypersensitivity reactions.

Case-1:A 69-year-old woman with stage III colon cancer received FOLFOX chemotherapy. During the first cycle, she developed flushing and pruritus at the 26th hour of continuous 5-FU infusion, which resolved with antihistamines and infusion rate reduction. Similar symptoms recurred during the second cycle despite premedication. Skin prick and intradermal tests with 5-FU were negative (Figure-1). Given the indispensable role of 5-FU, a one-bag 12-step desensitization protocol was initiated (Table-1), followed by continuous infusion, which was completed without adverse reactions.

Case-2: 60-year-old woman with stage III colon adenocarcinoma tolerated the first four cycles of FOLFOX uneventfully. During the fifth and sixth cycles, she developed tongue and palatal swelling approximately 24 hours into continuous 5-FU infusion, without urticaria or systemic involvement. Skin testing was negative (Figure-2) . Due to the lack of alternative chemotherapy options, a rapid one-bag desensitization protocol was performed(Table-2), followed by continuous infusion, which was well tolerated.

Discussion: To our knowledge, only two previous cases of 5-FU desensitization have been reported. In contrast to earlier reports, hypersensitivity reactions in our patients occurred exclusively during the continuous infusion phase rather than the bolus administration.Negative skin tests in both cases support a non-IgE-mediated mechanism. Isolated flushing in the first case and delayed, urticaria-free angioedema in the second case favor a non-IgE infusion-related hypersensitivity phenotype rather than classical IgE-mediated allergy.As no reactions occurred during bolus administration and recent data indicate comparable safety and efficacy between one-bag and three-bag protocols, a one-bag desensitization approach was preferred, allowing controlled titration without peak concentration exposure.

Conclusion: These cases demonstrate that 5-FU–related infusion hypersensitivity reactions, including delayed non-IgE-mediated presentations, can be safely managed using desensitization protocols. Awareness of infusion-phase reactions and individualized pharmacokinetic management are essential to maintain chemotherapy continuity in patients requiring 5-FU.