Clinical Status of Cisplatin, Carboplatin, and Other Platinum‐Based Antitumor Drugs

The platinum drugs represent a unique and important class of antitumor agents. The initial discovery of the antitumor properties of cisplatin by Dr. Barnett Rosenberg was quickly followed by clinical trials demonstrating its efficacy in a variety of solid tumors. It was soon realized, however, that nephrotoxicity and the emergence of drug-resistant tumor cells limited the overall efficacy of cisplatin. The search for new platinum analogues that could circumvent the deleterious aspects of cisplatin therapy soon followed. Carboplatin is a cisplatin analogue that is more easily administered and is less toxic at standard doses. This is due to a different pharmacokinetic profile resulting from the substitution of a more stable leaving group. Carboplatin and cisplatin form similar DNA adducts, which may explain, in part, the similar efficacies observed with the drugs in most solid tumors. The search for platinum analogues that do not exhibit cross-resistance with cisplatin and carboplatin has led to the synthesis of the DACH platinum compounds. The DACH platinum drug, oxaliplatin, has been shown to be active in combination with 5-fluorouracil and leucovorin for the treatment of colorectal cancer, a disease in which cisplatin and carboplatin show little activity. It appears that the clinical use of cisplatin and its analogues will continue to evolve, guided by pharmacologic principles, and these drugs will remain indispensable to combination chemotherapeutic regimens for many years to come.