Abstract 3064: Newer platinum agent, Triplatin NC, is as effective as Triplatin for metastatic breast cancer and pancreatic cancer carcinomatosis
Authors: Katsuta Eriko , DeMasi Stephanie C. , Katner Samantha J. , Aoki Hiroaki , Peterson Erica J. , Farrell Nicholas P. , Takabe Kazuaki 
Published: July 2016

Introduction: Since metastatic cancer is the most advanced disease and is associated with the worst outcome, an effective treatment for this Stage is expected to directly improve overall survival. 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, however, pharmacokinetics limited its clinical efficacy in Phase II clinical trials. Recent development of Triplatin NC resolved the PK issue, and it is expected to be more clinically useful if it is as effective as Triplatin with less cytotoxic properties.

Methods: HUVEC cells were used for tube formation assays. After orthotopic implantation of Murine breast cancer 4T1-luc2 cells, female Balb/C mice were randomized on Day 1 to Day 1, 5, 9 i.p. administration of Triplatin (0.3mg/kg), Triplatin NC (25mg/kg) or Saline and mice were sacrificed on Day 20 when lung metastasis was evaluated by ex vivo imaging. Pancreatic cancer carcinomatosis, generated by ip injection of 1 million Panc02-luc cells into C57/Blk6 mice. Animals were treated every 4 days beginning on day 1 by i.p. injection with either Triplatin (0.3mg/kg), Triplatin NC (25mg/kg) or Vehicle.

Results: IC50 of 4T1-luc cells at 72h were 9μM and 8μM for Triplatin and Triplatin NC, respectively. 10μM of Triplatin or Triplatin NC demonstrated significant suppression of tube formation compared from no treatment (p = 0.005 and p = 0.002, respectively). Additionally, 0.1μM of Triplatin NC demonstrated significant suppression of tube formation as well (p = 0.003). In 4T1-luc2 implanted model, bioluminescent imaging on Day 7 demonstrated reduced tumor growth in Triplatin and Triplatin NC to 54% and 57% of the control, respectively. By Day 20, Triplatin and Triplatin NC suppressed the tumor size to 20% and 43% of the control, respectively. Triplatin and Triplatin NC significantly reduced the amount of lung metastasis to 14% and 21% of the control, respectively.

In pancreatic cancer peritoneal carcinomatosis model, Triplatin and Triplatin NC reduced total tumor burden to 35% and 39% of the control on Day 9, respectively. Mouse survival was significantly enhanced by Triplatin treatment group in comparison with the control (p &lt; 0.005). All of Triplatin treatment mice survived more than 40 days, whereas all of control group mice died less than 35 days. No mouse developed weight loss more than 25%.

Conclusion: Both Triplatin and Triplatin NC effectively suppressed 4T1-luc2 breast cancer cell growth, and angiogenesis in vitro. Both agents demonstrated similar growth suppression not only of the primary tumor, but also in lung metastasis and panc02-luc carcinomatosis. New platinum compounds with less toxicity and favorable pharmacokinetics warrant further investigation for advanced metastatic cancer.

Citation Format: Eriko Katsuta, Stephanie C. DeMasi, Samantha J. Katner, Hiroaki Aoki, Erica J. Peterson, Nicholas P. Farrell, Kazuaki Takabe. Newer platinum agent, Triplatin NC, is as effective as Triplatin for metastatic breast cancer and pancreatic cancer carcinomatosis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3064.