A chemical perspective on the clinical use of platinum-based anticancer drugs

Abstract

Platinum drugs have been a mainstay of cancer chemotherapy since the introduction of cisplatin in the 1970s. Since then, carboplatin and oxaliplatin have been approved world-wide and nedaplatin, lobaplatin, heptaplatin, dicycloplatin, and miriplatin have been approved in individual countries. The three main platinum drugs are not used in isolation but are combined in chemotherapy protocols from a range of 28 drugs that include: anthracyclines, alkylating agents, vinca alkaloids, antimetabolites, topoisomerase inhibitors, taxanes, and monoclonal antibodies. Interestingly, they are not yet used in combination with tyrosine kinase inhibitors or proteasome inhibitors. How platinum drugs are formulated for administration to patients is important to minimise aquation during storage and administration. Cisplatin is typically formulated in saline-based solutions while carboplatin and oxaliplatin are formulated in dextrose. Pharmacokinetics are an important factor in both the efficacy and safety of platinum drugs. This includes the quantity of protein-bound drug in blood serum, how fast the drugs are cleared by the body, and how fast the drugs are degraded and deactivated. Attempts to control platinum pharmacokinetics and side effects using rescue agents, macrocycles, and nanoparticles, and through the design of platinum(IV)-based drugs have not yet resulted in clinically successful outcomes. As cancer is predominantly a disease of old age, many cancer patients who are administered a platinum drug may have other medical conditions which means they may also be taking many non-cancer medicines. The co-administration of non-cancer medicines to patients can potentially affect the efficacy of platinum drugs and/or change the severity of their side effects through drug–drug interactions.