Chapter 7

Dicycloplatin, a Platinum - Based Supramolecule with 4 Hydrogen Bonds,is a Promising Chemotherapy Drug

Xuqing Yang, Jing Jie Yu, Yi Guo and Michael D. Mueller

Abstract

Improving therapeutic efficacy and reducing adverse reactions of chemotherapeutic agents are primary goals of cancer research. Dicycloplatin (DCP), a next-generation platinum drug for cancer chemotherapy approved by the Chinese FDA in 2012, shows better solubility and stability than cisplatin and carboplatin. In preclinical in vitro and in vivo studies and a phase I clinical trial DCP demonstrated greater 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-plu- -paclitaxel comparable to carboplatin-plus-paclitaxel, but with better tolerability. DCP bio-pharmaceutical analysis showed different spectrum profiles of DCP and carboplatin in plasma. The bearable side effects of dicycloplatin might be due to the physicochemical properties of dicycloplatin, a supramolecule containing 4 hydrogen bonds. Furthermore, Histoculture Drug Response Assay and the successful treatment of a lung cancer patient with brain metastatic tumor indicate possible BBB penetration. Molecular studies of dicycloplatin-induced activation of DNA damage response, including Chk2, BRCA1 and p53, demonstrated a signaling pathway similar to cisplatin-induced activation. This chapter concludes with an early case-study report for the first American cancer patient to receive dicycloplatin chemotherapy. The patient was treated in Beijing in the summer of 2016. In conclusion, dicycloplatin is a promising next-generation platinum drug for cancer chemotherapy.

Total Pages: 339-362 (24)

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