Hindawi Publishing Corporation Metal-Based Drugs Volume 2010, Article ID 207084, 11 pages doi:10.1155/2010/207084 Review Article Hypersensitivity Reactions Associated with Platinum Antineoplastic Agents: A Systematic Review Nektaria Makrilia,1 Ekaterini Syrigou,1 Ioannis Kaklamanos,1 Leonidas Manolopoulos,1 and Muhammad Wasif Saif2 1 Oncology Unit, 3rd Department of Medicine, Sotiria General Hospital, Athens University School of Medicine, Mesogion 152, 115 27 Athens, Greece 2 Department of Clinical Oncology, Yale University School of Medicine, New Haven, CT 06510, USA Correspondence should be addressed to Nektaria Makrilia, makmacs@hotmail.com Received 20 May 2010; Accepted 14 July 2010 Academic Editor: Andrea Bonetti Copyright © 2010 Nektaria Makrilia et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Platinum-containing chemotherapy agents (cisplatin, carboplatin, oxaliplatin) have been approved in the ﬁrst-line setting of numerous malignancies, such as ovarian, bladder, head and neck, colorectal, and lung cancer. Their extensive use over the last decade has led to a signiﬁcant increase in the incidence of hypersensitivity reactions, which are deﬁned as unforeseen reactions whose signs and symptoms cannot be explained by the known toxicity of these drugs. Skin rash, ﬂushing, abdominal cramping, itchy palms, and back pain are common symptoms. Cardiovascular and respiratory complications can prove fatal. Multiple pathogenetic mechanisms have been suggested. Hypersensitivity usually appears after multiple infusions, suggesting type I allergic reactions; however, other types of hypersensitivity also seem to be implicated. Several management options are available to treating physicians: discontinuation of chemotherapy, premedication, prolonging of infusion duration, desensitization protocols, and replacement with a diﬀerent platinum compound after performing skin tests that rule out cross-reactions among platinum agents. 1. Introduction Platinum-based compounds were ﬁrst synthesized in the nineteenth century but their clinical use against cancer did not start until the 1970s. Their activity consists of forming DNA addicts that inhibit replication and lead to apoptosis [1, 2]. They have been approved for the treatment of numerous malignancies, such as ovarian, primary peritoneal carcinoma, bladder, head and neck, colorectal, pancreatic, esophageal, gastric, testicular, endometrial, biliary tract, and lung cancer and mesothelioma [3–15]. Platinum agents are also eﬀective in pediatric tumors [16, 17]. They are used in the ﬁrst-line and adjuvant setting but also as retreatment regimens when there is a long progression-free interval after treating with the same drugs [18, 19]. Cisplatin [(SP-4-2)-diamminedichloroplatinum] was the ﬁrst of the platinum drugs to be used and is characterized by neurotoxicity, nephrotoxicity, ototoxicity, and eme- togenicity [1]. Second-generation platinum derivative carboplatin [cis-diammine (cyclobutane-1,1-dicarboxylate- O, O )platinum(II)] diﬀers from cisplatin in the substitution of two chlorides by a 1,1-cyclobutane dicarboxylate group. Its eﬃcacy in the treatment of many of the above malignancies is equal to that of cisplatin, and its toxicity proﬁle is more favorable [20]. Thus, carboplatin has often been used in place of cisplatin [21, 22]. Oxaliplatin [[(1R,2R)-cyclohexane- 1,2-diamine](ethanedioate-O,O )platinum(II)] is a third- generation platinum compound widely used for the treatment of metastatic colorectal cancer and a variety of other malignancies, such as breast cancer, melanoma, non- Hodgkin lymphoma, and head and neck cancer [23–25]. Common adverse events are myelotoxicity, nausea, vomiting diarrhea, paresthesia, and dysesthesias [26–28]. Hypersensitivity to a chemotherapeutic agent is deﬁned as an unforeseen reaction whose signs and symptoms cannot be explained by the known toxicity of the drug [29]. Indus- trial complex platinum salts have been reported to cause hypersensitivity and asthma among reﬁnery workers since