P0179 Severe hypersensitivity reactions with original and generic taxanes: A prospective study at a medical oncology unit in Thailand

Abstract

<h3>Background</h3> Taxanes, including docetaxel and paclitaxel, are commonly used in various types of malignancies. A well-known adverse event of taxanes is hypersensitivity reaction during administration. Solvents and other inactive ingredients were thought to be the cause of this reaction. Given minor differences between original and generic parenteral drugs, we compared the incidences of grade 3 and 4 hypersensitivity reactions between original and generic taxanes. <h3>Methods</h3> In this prospective study, all patients receiving taxanes between January 1 and December 31, 2013 at King Chulalongkorn Memorial Hospital were enrolled. Using the taxane hypersensitivity reaction case record form, we recorded the product, event, symptom, and treatment for each event. Hypersensitivity reactions and grading were defined by Common Terminology Criteria for Adverse Events (CTCAE) Version 3.01. The study primarily compared the grade 3 and 4 hypersensitivity reaction incidences between original and generic taxanes. <h3>Findings</h3> Among the total 258 patients, 130 patients received docetaxel (66 in its original formulation and 64 in generic form) and 128 patients received paclitaxel (65 in its original formulation and 63 in generic form). All patients received premedication including antihistamine and dexamethasone 30min before taxane infusion and surveillance for hypersensitivity reactions. There were 26 (10.0%) grade 3 hypersensitivity reaction events reported, but no grade 4 hypersensitivity reactions. With docetaxel, there were nine grade 3 reactions to the original formulation and one grade 3 to the generic form (<i>p</i>=0.017). With paclitaxel, there were nine grade 3 reactions with the original formulation and seven grade 3 reactions with the generic form (<i>p</i>=0.791). The most common symptoms of hypersensitivity were flushing and chest discomfort. Twenty (77%) of all reactions received rescue medication, including antihistamine and corticosteroid intravenously. No life-threatening symptom or permanent discontinuation of taxanes had occurred. Unexpectedly, only 23% of the reactions were observed in first cycle. <h3>Interpretation</h3> In this prospective study, hypersensitivity reactions to taxanes were more common than in previous retrospective reports. In our cohort, the incidences of grade 3 or 4 hypersensitivity reaction were not different between original and generic paclitaxel but higher with original docetaxel than with generic docetaxel. First hypersensitivity reactions in later cycles of treatment were not uncommon.