Dicycloplatin (DCP) has better solubility and stability than both
cisplatin and
carboplatin. Pre-clinical and phase I studies demonstrated significant antitumor activity and fewer adverse events than
carboplatin. Phase II clinical trials in advanced
non-small cell lung cancer found efficacy and safety of DCP-plus-
paclitaxel comparable to
carboplatin-plus-
paclitaxel but better tolerability. This article summarizes and reviews pre-clinical and clinical data for
dicycloplatin from the Chinese medical literature. We also report on new mechanistic findings in our laboratory in West Virginia, USA. Patient blood samples were collected for DCP-prototype determination by liquid chromatography mass spectrometry (LC-MS/MS). Molecular studies of
ovarian cancer cells treated with DCP or
cisplatin were carried out for gene-signature profiling using immunoblotting. Pharmacokinetic mass-spectrometry showed different spectrum profiles of DCP and
carboplatin in plasma. Plasma concentration of DCP prototype was 17.1 μg/ml 2h after administration, with a peak concentration of 26.9 μg/ml at 0.5 h. Immunoblotting showed DCP-induced activation of DNA damage pathways, including double-phosphorylated
checkpoint kinase 2 (CHK2) and
breast cancer 1 (BRCA1) and triple-phosphorylated p53, compared to controls.
Cisplatin produced a similar profile, with increased p53
protein. DCP and
cisplatin activate DNA-damage response through similar pathways. DCP may be more soluble and stable, and better-tolerated.