Abstract 5117: Triplatin preferably suppress lung metastasis of breast cancer, and peritoneal carcinomatosis of colon and pancreatic cancer

Background: Since metastatic spread is often directly associated with the poor outcome, an effective treatment for metastatic lesion is expected to improve overall survival. This is particularly the case in peritoneal carcinomatosis of pancreatic cancer where there is no effective treatment. Recent clinical trials demonstrated that Cisplatin is effective in certain metastatic breast cancer, however with severe side effects. Polynuclear platinum analog, Triplatin, was developed to overcome the severe toxicity. Methods: Murine cancer cell lines, 4T1-luc2 and E0771 (breast), Panc02-luc (pancreas) and CT26-luc (colon) were used. Cell proliferation was quantified by CCK8 assay. Syngeneic orthotopic implantation of 4T1-luc2 cells was used for metastatic breast cancer model. For mastectomy model, primary tumors were surgically removed 8 days after inoculation. Syngeneic intraperitoneal injection of CT26-luc cells and Panc02-luc cells were used for peritoneal carcinomatosis models of colon and pancreatic cancer respectively. Triplatin (0.3 mg/kg) or vehicle was administered intraperitoneally every four days three times and tumor burden was quantified by bioluminescence imaging. Results: Triplatin suppressed cell growth of both breast cancer and pancreatic cancer in a dose dependent manner in vitro (IC50 of 4T1-luc2, E0771 and Panc02-luc cells were 0.08, 0.51 and 0.07 μM, respectively). Triplatin did not suppress the growth of 4T1-luc2 primary breast tumor, however, ex vivo results showed that lung metastases were significantly reduced to 14% of the control (p = 0.034) in orthotopic model. This result was reproduced in post-mastectomy “adjuvant therapy” model where Triplatin treatment was began after primary implanted tumor was removed, which suppressed lung metastases down to 1.9% of control by Day21 (p = 0.038), and significantly prolonged survival (p = 0.007). This result led us to use Triplatin in CT26-luc colon cancer carcinomatosis model, where Triplatin suppressed total tumor burden to 1.9% of control by Day13 (p = 0.029) and significantly prolonged survival (p = 0.001). Finally, Triplatin reduced total tumor burden of Panc02-luc pancreatic cancer peritoneal carcinomatosis model to 35% of the control by Day 9 (p = 0.337) and the survival was significantly prolonged (p = 0.025). Conclusion: Triplatin demonstrated significant suppression lung metastatic tumor of 4T1-luc2 breast cancer, and peritoneal carcinomatosis of CT26-luc colon cancer and Panc02-luc pancreatic cancer. Newer platinum compounds with less toxicity and favorable pharmacokinetics warrant further investigation for advanced metastatic cancer. Citation Format: Eriko Katsuta, Erica J. Peterson, Samantha J. Katner, Nicholas P. Farrell, Kazuaki Takabe. Triplatin preferably suppress lung metastasis of breast cancer, and peritoneal carcinomatosis of colon and pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5117. doi:10.1158/1538-7445.AM2017-5117