The Novel Platinum Analog Dicycloplatin Provides Reliable Growth Inhibition of Urothelial Carcinoma Cells In Vitro.

ABSTRACT

BACKGROUND/AIM: Platinum-based chemotherapies are a component of standard-of-care regimens for urothelial carcinoma (UC). These nephrotoxic drugs are often dose-limiting, with cisplatin and carboplatin being the most commonly used. Dicycloplatin (DCP) has better solubility and stability, with comparable efficacy and better tolerability. Some suggest the use of DCP as primary treatment for non-muscle-invasive bladder cancer. We exposed UC cell lines to DCP in vitro to assess its efficacy. MATERIALS AND METHODS: A high grade (IV) in vitro UC cell line (TCCSUP) was exposed to varying concentrations of cisplatin (0-600 µg/ml), carboplatin (0-600 µg/ml), oxaliplatin (0-4.0 µg/ml), and DCP (0-350 µg/ml). Grade II-IV cells were exposed to varying concentrations of DCP (0-350 µg/ml) to assess time- and concentration-dependent growth inhibition, and simulate intravesical treatment. Growth inhibition was determined following 24, 48, and 72 h of exposure, using a tetrazolium dye to assess mitochondrial dehydrogenase activity. RESULTS: DCP, cisplatin, and carboplatin effectively achieved >90% cell kill at 72 h. Concentrations of 325 µg/ml DCP, 50 µg/ml cisplatin, and 600 µg/ml carboplatin were sufficient for >90% cell-kill, with cisplatin demonstrating the highest efficacy at the lowest concentration/time intervals. Dose- and time-dependent cell kill were demonstrated at varying concentrations of DCP in grade II-IV cell lines, including cells exposed intravesically. CONCLUSION: In vitro, DCP demonstrates cell-killing efficacy in a time- and concentration-dependent manner in grade II-IV UC cell lines, showing promise for its intravenous, oral, and intravesical use for bladder UC in both primary and adjuvant/neoadjuvant settings.