INTRODUCTION
5-Fluorouracil (5-FU) is a chemotherapeutic agent widely used in the treatment of gastrointestinal tract, skin and breast cancers [1]. Hypersensitivity reactions may occur due to the use of chemotherapeutic drugs. The underlying mechanisms of hypersensitivity reactions to chemotherapeutic drugs are not clear and depend on the drugs. Hypersensitivity reactions may develop with both immunological and non-immunological mechanisms. Most often type 1 immunological, rarely type 2 (haemolytic anemia) and may occur with type 3 reaction (vasculitis). Life-threatening hypersensitivity reactions to 5-FU are rare in the literature.
AIM
The case is here presented of a patient with metastatic gastric cancer who developed anaphylaxis during systemic 5-FU administration and was successfully desensitized to 5-FU.
CASE REPORT
A 69-year-old male had been diagnosed with metastatic gastric cancer 2 years previously and was treated with chemotherapy and radiotherapy. As there was disease progression after six courses of chemotherapy, a new chemotherapy protocol containing 5-FU was prescribed to the patient in the oncology clinic. The patient received the first 5-FU course without any problems, then within 10 min of the second infusion, shortness of breath, facial erythema, abdominal pain, nausea, vomiting, hypotension (blood pressure: 70/30 mm Hg) and syncope occurred. The patient was administered 80 mg methylprednisolone and 45.5 mg pheniramine intravenously and 0.5 mg adrenaline intramuscularly in the oncology clinic. After the adrenaline administration, symptoms of the patient resolved in 2 h. Four weeks after the allergic reaction, the patient was admitted to the adult allergy clinic. The patient had no other comorbid disease or drug allergy, or atopy history before. Skin prick (1 mg/ml dilution) and intradermal tests (0.1, 0.01 and 0.001 mg/ml dilutions) were applied to the patient. Histamine (10 mg/ml) was applied as a positive control and saline as a negative control. The skin prick and intradermal tests were evaluated after 20 min. There was no induration diameter of 3 mm or more, so the skin prick and intradermal tests were evaluated as negative. The oncologist was consulted and the patient was desensitized to 5-FU because he had to receive 5-FU chemotherapy. Dexamethasone (20 mg, 6 h before infusion) and famotidine (20 mg, 30 min before infusion) were administered as premedication before desensitization. No allergic reaction was observed during desensitization. The desensitization protocol is shown in Table 1. The patient received a total of four courses of 5-FU chemotherapy with a desensitization protocol without developing any allergic reaction.
TABLE 1
Intravenous desensitization protocol to 5-fluorouracil. Target dose: 650 mg 5-fluorouracil. Solutions: Solution 1: 6.5 mg 5-fluorouracil in 250 ml dextrose (5%) (1/100 dilution), Solution 2: 65 mg 5-fluorouracil in 250 ml dextrose (5%) (1/10 dilution), Solution 3: 643.5 mg (650-6.5 mg) 5-fluorouracil in 250 ml dextrose (5%) (1/1dilution). Premedication: dexamethasone: 20 mg, 6 h before infusion, Famotidine: 20 mg, 30 min before infusion
| Step | Solution | Rate [ml/h] | Time [min] | Amount [ml] |
|---|---|---|---|---|
| 1 | 1 | 2.5 | 15 | 0.625 |
| 2 | 5 | 15 | 1.25 | |
| 3 | 10 | 15 | 2.5 | |
| 4 | 20 | 15 | 5 | |
| 5 | 2 | 5 | 15 | 1.25 |
| 6 | 10 | 15 | 2.5 | |
| 7 | 20 | 15 | 5 | |
| 8 | 40 | 15 | 10 | |
| 9 | 3 | 10 | 15 | 2.5 |
| 10 | 20 | 15 | 5 | |
| 11 | 40 | 15 | 10 | |
| 12 | 75 | 186 | 296 |
DISCUSSION
To the best of our knowledge, this is the second case report in the literature of successful desensitization to 5-FU. The patient received a total of four courses of 5-FU chemotherapy with a 12-step desensitization protocol without any allergic reaction. The hypersensitivity reaction occurring in the patient was evaluated as type 1 hypersensitivity reaction. The hypersensitivity reaction was accepted as grade 5 anaphylaxis [2, 3]. The risk of hypersensitivity reaction may be increased because the patient had a history of multiple chemotherapy treatments. Eppinger and Sperber described the first successful desensitization in a patient who developed anaphylaxis after 5-FU infusion [4]. In that case, 5 min after the first intravenous 5-FU administration, the patient had shortness of breath, chest tightness, angioedema on the lips and itching. Premedication was given before the second intravenous 5-FU administration and an allergic reaction occurred again. The patient was desensitized to 5-FU after the intradermal test with 0.01 mg/ml concentration was found to be positive [4]. In the current case, the skin prick and intradermal tests were found to be negative. Negative skin tests suggest that the reaction may occur due to non-IgE type 1 hypersensitivity. An infusion reaction was not considered because the reaction did not occur in the first infusion, there was no accompanying high fever, and there was accompanying hypotension.
Early type hypersensitivity reactions to 5-FU are uncommon in reports in the literature. Sridhar reported a case of angioedema after administration of 5-FU [5]. Millá Santos, Biswal and DeBeer reported cases of anaphylaxis following 5-FU administration [6–8]. Late and life-threatening hypersensitivity reactions to 5-FU have also been described in the literature [1, 9] as have cases of allergic contact dermatitis following topical 5-FU treatment [10–12].
