Table 2: Types of hypersensitivity reactions, their characteristics, and how they are implicated in platinum agent hypersensitivity. Mast cell and basophil degranulation Carboplatin, Cisplatin, Oxaliplatin (most) 3 Symptoms related Early onset symptoms: itching, chest pain, rash, anaphylactic reactions Hemolysis, thrombocytopenia Chronic urticaria, joint pain, proteinuria Delayed reactions, hours or even days after infusion Antigen Mediated by Mechanism Soluble antigen Cell- or matrix- associated antigen Soluble antigen Soluble or cell-associated antigen IgE IgG, IgM IgG T-cells (TH1, TH2, Cytotoxic T cells) Phagocyte and NK-cell activation Immune complexes, Phagocyte and NK-cell activation, complement ﬁxation Macrophage and eosinophil activation, cytotoxicity Involved in platinum hypersensitivity Oxaliplatin Oxaliplatin Carboplatin, Cisplatin Metal-Based Drugs Type of hypersensitivity I II III IV Table 3: Emergency procedures in case of hypersensitivity reactions. Emergency procedures in case of hypersensitivity reaction to a platinum agent (1) Interruption of infusion (2) Administer: i.v. antihistamines (type 1 and 2 histamine receptor antagonists), normal saline infusion, and low-dose corticosteroids (antihistamines are the ﬁrst to be administered) (3) In case of a more severe reaction (dyspnoea, laryngospasm, bronchospasm): (i) oxygen, bronchodilators (ii) high dose steroids (doses range between 100 and 1000 mg of hydrocortisone) (4) Administer epinephrine in case of hypotension or airway obstruction symptoms (5) Monitoring until symptoms resolve or for several hours later in case of severe hypersensitivity combined with. More speciﬁcally, the CALYPSO trial showed that hypersensitivity reactions occurred more frequently in patients receiving carboplatin-paclitaxel, as compared to patients on a combination of carboplatin with pegylated liposomal doxorubicin (PLD) (18.8% versus 5.6%, resp.) [74]. Markman et al. also reached the conclusion that administering PLD with carboplatin substantially reduces the incidence of carboplatin-associated hypersensitivity [75]. In oxaliplatin regimens, younger age, female sex, and use of this platinum compound as salvage therapy have recently been recognized as potential risk factors [46] as opposed to type and number of metastatic sites [45]. 4. Pathophysiology The exact mechanism of platinum allergy remains unclear (Table 2) although multiple studies have tried to explain the underlying pathophysiology. Reactions are thought to be mainly caused by type I IgE-mediated or type IV T-cell- mediated hypersensitivity. Nevertheless, the presentation pattern of these reactions is unpredictable, suggesting that various immunological and nonimmunological mechanisms are involved [30]. In type I hypersensitivity reactions, IgE immunoglobulin causes the degranulation of mast cells and basophils leading to the nonimmune-mediated histamine and cytokine release [32, 38, 76, 77]. Early-onset symptoms, such as itching, chest pain, rash, and anaphylactic reactions are attributed to this pathway [32]. Hypersensitivity in exposed reﬁnery workers [30, 39], the need of multiple infusions for sen- sitization, and positive carboplatin skin tests are in favor of the above hypersensitivity mechanism but no study has searched for platinum-speciﬁc IgE [30, 78, 79]. Type IV hypersensitivity to platinum agents also seems to be involved. Antigens binding to the major histocompatibility complex activate T cells that have already been sensitized. This hypersensitivity is associated with the delayed inﬂammatory reaction presenting hours or even days after the infusion [32, 80]. Increased production of cytokines, such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-6, might be caused by platinum compounds acting as superantigens, but this has yet to be proven [80, 81]. According to the latest hypersensitivity models, serotonin is also implicated in anaphylactic mechanisms, and this could explain the symptoms of hypertension and bronchospasm [82]. As far as oxaliplatin is concerned, most reactions seem to be IgE-mediated but type II hypersensitivity is also implicated with the presentation of hemolysis and thrombocytopenia [83]. Chronic urticaria, joint pain, and proteinuria after oxaliplatin regimens have been attributed to type III allergic reactions [73]. Furthermore, idiosyncratic reactions characterized by chills, fever, abdominal cramps, and chest tightness have been described during the infusion [81, 84, 85]. The development of carboplatin hypersensitivity after a median number of eight therapy courses has been attributed