The state-of-play and future of platinum drugs Michael G Apps, Eugene H Y Choi and Nial J Wheate Faculty of Pharmacy, The University of Sydney, Sydney, New South Wales 2006, Australia Correspondence should be addressed to N J Wheate Email nial.wheate@sydney.edu.au Abstract The year 2015 marks the 50th anniversary since the discovery of the anticancer potential of cisplatin and it remains just as useful now as it did back then, especially for the treatment of some endocrine-related cancers like ovarian and testicular carcinomas. Since its discovery, five other platin drugs have received approval in various countries. While several new platin drugs are in preclinical development, in the last decade only two new platin drugs have entered clinical trials, LA-12 and dicycloplatin, reflecting a shift in research focus from new drug design to improved formulations of already approved platin drugs. These formulations include their encapsulation with macrocycles to slow and prevent their degradation by proteins and peptides; their attachment to nanoparticles to passively target solid tumours through the enhanced permeability and retention effect and their coordination to important nutrients, proteins, antibodies and aptamers for active tumour targeting. These formulation methods have all shown potential but none have yet yielded a new marketable medicine containing a platin drug. The reasons for this are problems of consistent drug loading, controlling the location and timing of drug release and the inherent toxicity of some of the drug delivery vehicles. In addition to drug delivery, functional genomics is now playing an increasing role in predicting patients’ responses to platin chemotherapy and their likelihood of experiencing severe side effects. Key Words " cancer " cisplatin " formulation " drug delivery " functional genomics Endocrine-Related Cancer (2015) 22, R219–R233 Introduction While cisplatin was first synthesised in 1844, the antic- ancer potential of cisplatin was not discovered by accident until 1965 (Kauffman et al. 2010). It was approved for use in 1978 and since then another 25 platin drugs have entered clinical trials, with two, oxaliplatin and carbo- platin, gaining broadly worldwide approval and another three gaining approval in single markets; nedaplatin in Japan, lobaplatin in China and heptaplatin in Korea (Wheate et al. 2010)(Fig. 1). Despite a claim that 50–70% of all patients receive a platinum drug (Sava & Dyson 2006), which has been repeated by others (Harper et al. 2010, Zalba & Garrido 2013), there is no evidence on how many patients actually receive these drugs. Only the overall number of chemother- apy regimens that include a platin drug is known with any accuracy; based on Martindale and the Australian EviQ database, w50% of all chemotherapy schedules include a platinum drug (Wheate et al. 2010). Platinum drugs are used to treat a wide variety of cancers, including some endocrine- related cancers: testicular and ovarian carcinomas. They are also used to treat melanoma, small-cell and non-small-cell lung cancer, myelomas and lymphomas. The generic names of all platinum-based drugs end with ‘platin’, and henceforth, this abbreviation will be Endocrine-Related Cancer Review M G Apps et al. The state-of-play and future of platinum drugs 22 :4 R219–R233 http://erc.endocrinology-journals.org q 2015 Society for Endocrinology DOI: 10.1530/ERC-15-0237 Printed in Great Britain Published by Bioscientifica Ltd.