Abstract 290: Formulation of tolerable protocols for combination regimens to control triple-negative breast cancer cell-derived xenograft tumor development in animals

Cumulative research and clinical results suggest an advantage to use a multiple drug combination over a single drug to control tumor growth and metastasis. In general, combination therapy may result in lower treatment failure rates, lower case fatality ratios, slower development of resistance, and fewer side effects than monotherapy, as well as reducing cost. Triple-negative breast cancer (TNBC) is aggressive, lethal, and heterogeneous. The molecular heterogeneity may account for the differential responses of TNBC to chemotherapies. TNBC is sensitive to conventional chemotherapies with initially high response rates; however, the prognosis is not optimal due to cancer recurrence and metastasis. Although recent advancements in drug development of targeted therapeutics and immunotherapy were somewhat effective in treating TNBC, these therapeutics still need extensive study. Although combination regimens are thought to have better therapeutic outcomes than single drug treatments, drug combinations may also come with overlapped toxicities. Thus, it is important to identify combination regimens that are safe and effectively treat cancers. Based on our in vitro results of combination regiments effective in the synergistic induction of TNBC cell death, we systemically investigated the toxicity and efficacy of combined triple and double agents at various doses and administration protocols to assess the treatment of mice bearing TNBC cell-derived xenograft tumors. We analyzed the adverse effects of combination regimens on the bone marrows, livers, and kidneys, as well as the blood cell profiles in immune-competent and -deficient mice. Our studies successfully identified tolerable protocols for triple and double combination regimens of gemcitabine, romidepsin, and cisplatin, which are FDA-approved anticancer agents, as well as the efficacy of these combination regimens in controlling TNBC xenograft tumors in immune-deficient mice. Our results indicated that the triple combination of gemcitabine plus romidepsin and cisplatin regimen was more effective than double combination regimens in the control of TNBC tumor development in vivo. In conclusion, our studies suggested that the triple combination regimens should be promptly considered as an advanced treatment of TNBC over the conventional gemcitabine and cisplatin regimen or the clinical trial romidepsin plus cisplatin regimen. Citation Format: Pawat Pattarawat, Shelby Wallace, Agricola Odoi, Bianca Pfisterer, Hwa-Chain R. Wang. Formulation of tolerable protocols for combination regimens to control triple-negative breast cancer cell-derived xenograft tumor development in animals [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 290.