Hypersensitivity Reactions to Platinum Agents and Taxanes

Abstract

Hypersensitivity reactions (HSRs) to chemotherapy agents can present a serious challenge to treating patients with preferred or first-line therapies. Allergic reactions through an immunologic mechanism have been established for platinum and taxane agents, which are used to treat a wide variety of cancers including gynecologic cancers. Platin HSRs typically occur after multiple cycles of chemotherapy, reflecting the development of drug IgE sensitization, while taxane HSRs often occur on first or second exposure. Despite observed differences between platin and taxane HSRs, drug desensitization has been an effective method to reintroduce both chemotherapeutic agents safely. Skin testing is the primary diagnostic tool used to risk-stratify patients after initial HSRs, with more widespread use for platinum agents than taxanes. Different practices exist around the use of skin testing, drug challenge, and choice of desensitization protocol. Here, we review the epidemiology, mechanism, and clinical presentation of HSRs to platinum and taxane agents, as well as key controversies in their evaluation and management.

Keywords: Chemotherapy; Desensitization; Drug allergy; Hypersensitivity; Platinum agent; Taxane.

Fig. 1

Mechanisms of immediate HSRs to platins and taxanes. Phenotypes of platin HSRs include type I reactions, cytokine release reactions, and mixed reactions, with the most heterogeneity seen with oxaliplatin (A). Taxanes may cause mast cell and/or basophil activation through IgE-mediated mechanisms, direct action on basophils, or IgG-mediated mechanisms that cause complement activation and release of anaphylatoxins (C3a, C5a) (A, B). Solvents for taxanes, such as Cremophor EL (paclitaxel) and polysorbate 80 (docetaxel), may also activate mast cells through an IgE-mediated mechanism or direct complement activation. Biomarkers include tryptase, histamine, leukotrienes, and prostaglandins in type I reactions and IL-6, TNF-α, and IL-1ß in cytokine release or mixed reactions (A, B). Desensitization is indicated for type I reactions and selected cases of cytokine release and mixed reactions, but not in direct mast cell/basophil activation (A). LTC4 leukotriene C4, PGD2 prostaglandin D2. Reproduced from Fig. 1 in Castells [65] and Fig. 3 in Picard and Castells [15] with permission

Fig. 2

Approach to reintroduction of taxanes after HSRs. Patients with a history of severe cutaneous adverse drug reactions (SCARs) including Stevens-Johnson syndrome and blistering skin reactions should avoid taxanes. Grading of immediate HSR severity is based on Brown’s classification. Patients with delayed or grade 1 immediate HSRs with negative skin testing (ST −) can undergo challenge. The decision to perform desensitization or challenge in patients with grade 2 immediate HSRs who are ST − is based on patient comorbidities and comfort with the procedure. Patients with grade 3 HSRs, regardless of ST result, undergo desensitization. Institutions that do not have access to ST can follow the protocol for ST + patients. Patients who do not have breakthrough HSRs during the initial protocol can subsequently be treated with a shorter desensitization protocol, challenge, or regular infusion according to the algorithm. For patients who experience breakthrough HSRs, adjustments can be made to premedications and length of protocol. Reproduced from Fig. 1 in Picard et al. [32] with permission