The side effects of platinum-based chemotherapy drugs: a review for chemists

Abstract

The platinum-based drugs cisplatin, carboplatin and oxaliplatin are regularly prescribed in the treatment of cancer and while they are effective, their use is limited by their severe, dose-limiting side effects (also referred to as adverse effects/events). In total, a cancer patient can experience any combination of around 40 specific side effects. The dose-limiting side effect for cisplatin is nephrotoxicity, for carboplatin it is myelosuppression, and for oxaliplatin it is neurotoxicity. Other common side effects include anaphylaxis, cytopenias (including leukopenia and neutropenia, thrombocytopenia, and anaemia), hepatotoxicity, ototoxicity, cardiotoxicity, nausea and vomiting, diarrhea, mucositis, stomatitis, pain, alopecia, anorexia, cachexia, and asthenia. The side effects may require patients to be prescribed dose reductions in their platinum drugs of between 25 and 100%. Furthermore, patients require extensive monitoring of their biochemistries, kidney and liver function, and depending on the drug, hearing tests. Finally, patients are commonly co-prescribed additional non-chemotherapy based drugs to treat the side effects which can include antiemetics, antibiotics and myeloid growth factors, mannitol, propafenone, saline hyperhydration, magnesium supplements, monoclonal antibody cytokine blockers, and antioxidants.

Retracted: Studies of proteasome inhibition and antitumor activity by novel amino acid‐polypyridine‐copper complexes

“…However, their negative side‐effects and the risk of resistance remain a pressing matter in their clinical use. These issues drive the research and development of new metallotherapeutics, in many cases, divergent from the platinum‐based complexes . Copper is biocompatible and less toxic that non‐endogenous heavy metals, furthermore, copper is an interesting candidate for the treatment of cancers because of its bioavailability and the observation of increased copper level in cancer tissue .…”

Iron(III) bis‐complexes of Schiff bases of S‐methyldithiocarbazates: Synthesis, structure, spectral and redox properties and cytotoxicity

“…Cisplatin is widely used as a metal‐based drug in the treatment of cancer and the second‐generation platinum drugs such as carboplatin, nedaplatin and oxaliplatin are being increasingly used for treating a variety of cancers . There are severe side effects like ototoxicity, nephrotoxicity, peripheral neuropathy and neurotoxicity, nausea, and myelotoxicity, that arise when platinum‐based complexes are used as anticancer drugs . Therefore to overcome the side effects new non‐platinum‐based drugs are being designed, synthesized and studied .…”

Tandem mass spectrometry characterization of a conjugate between oleuropein and hydrated cis‐diammineplatinum(II)

“…The resulting cis ‐DAP‐DNA adducts ultimately kill the cancerous cells through transcription inhibition and subsequent downstream effects . Unfortunately, poor selectivity toward healthy cells, drug‐resistance and acute nephrotoxicity are the main dose‐limiting side effects of CP …”