Platinum drugs are a class of chemotherapy medicines that treat cancer by forming platinum-DNA crosslinks that prevent cancer cells from copying their DNA and dividing, and the most commonly used agents are cisplatin, carboplatin, and oxaliplatin[6][3].
How platinum drugs work
– Platinum atoms in these drugs bind to DNA and create crosslinks between DNA strands or within a strand, which distorts DNA structure and blocks replication and transcription, triggering cell death pathways in rapidly dividing tumor cells[6][3].
– Because the damage they cause is physical (chemical adducts) rather than targeting a single protein, platinum agents are effective across many cancer types but also allow cells with efficient DNA repair to survive, which contributes to resistance[6][7].
Common platinum drugs and typical uses
– Cisplatin: a foundational platinum drug used for testicular, ovarian, bladder, lung, and other solid tumors; notable for strong antitumor activity but significant toxicities such as kidney damage and nerve toxicity[1][6].
– Carboplatin: a related drug with similar antitumor mechanisms but generally less kidney toxicity and greater bone marrow suppression; commonly substituted for cisplatin in regimens where nephrotoxicity must be limited[1][6].
– Oxaliplatin: structurally distinct (contains a diaminocyclohexane ring) and widely used in colorectal cancer as part of the FOLFOX regimen; it can be active against some tumors resistant to cisplatin or carboplatin[3][6].
How they are given and combined
– Platinum drugs are given intravenously and are frequently combined with other cytotoxic or targeted agents to improve efficacy; oxaliplatin for colorectal cancer is typically given with 5-fluorouracil and leucovorin (FOLFOX)[3][6].
Side effects and toxicity management
– Common acute effects include nausea, vomiting, and fatigue; specific toxicities vary: cisplatin causes notable nephrotoxicity and neurotoxicity, carboplatin more often causes myelosuppression, and oxaliplatin can cause a characteristic cold-induced neuropathy[1][3][6].
– Toxicities are managed with hydration, antiemetics, dose adjustments, and switching agents when necessary to balance benefit and harm[1][6].
Resistance to platinum therapy and current responses
– Tumor resistance arises through multiple mechanisms: enhanced DNA repair, changes in drug uptake or efflux, detoxification by cellular thiols, epigenetic changes, and metabolic reprogramming[7][6].
– Research seeks to overcome resistance by combining platinum drugs with agents that inhibit DNA repair, using alternative delivery or dosing, and developing nonplatinum approaches such as antibody-based or other targeted immunotherapies that may work against platinum-resistant tumors[2][7].
Research directions and alternatives
– New strategies include combining platinum agents with drugs that block DNA repair pathways or immune evasion, and investigating completely different therapies for platinum-resistant disease; for example, antibody-based approaches have shown potential against platinum-resistant ovarian cancer cell lines in preclinical studies[2][7].
– Nonplatinum experimental approaches (for example, novel targeted drugs or combinations) are explored to reduce toxicity and bypass platinum resistance mechanisms[2][4].
Practical considerations for patients
– Choice of platinum agent and whether to include one in a regimen depends on cancer type, stage, prior treatments, organ function (especially kidney and bone marrow), and patient goals; clinicians weigh expected benefit against known toxicities[1][3][6].
– Patients receiving platinum chemotherapy are monitored with blood tests for kidney and marrow function and assessed for neuropathy and other side effects so doses or agents can be adjusted[1][6].
Sources
https://pubmed.ncbi.nlm.nih.gov/41351339/
https://pubmed.ncbi.nlm.nih.gov/41376855/
https://www.britannica.com/science/oxaliplatin
https://int.livhospital.com/12-key-alkylating-agents-examples-in-chemotherapy-what-you-need-to-know/
https://www.nature.com/articles/s41598-025-30099-x