Makoto Asano1, Junji Matsui1, Murray J Towle2, Jiayi Wu3, Sharon McGonigle3, Marc Hillairet DE Boisferon4, Toshimitsu Uenaka5, Kenichi Nomoto6, Bruce A Littlefield7. 1. Oncology Business Group, Eisai Co., Ltd., Tsukuba, Japan. 2. Oncology Business Group, Eisai Inc., Andover, MA, U.S.A. 3. Neurology Business Group, Eisai Inc., Andover, MA, U.S.A. 4. Oncodesign, Dijon, France. 5. Morphotek, Exton, PA, U.S.A. 6. Oncology Business Group, Eisai Inc., Woodcliff Lake, NJ, U.S.A. 7. Oncology Business Group, Eisai Inc., Andover, MA, U.S.A. bruce_littlefield@eisai.com.
Abstract
BACKGROUND: Eribulin is used in many countries to treat patients with advanced breast cancer or liposarcoma and exerts in vivo anticancer activity under monotherapy conditions against various human tumor xenograft models. Here, eribulin in combination with mechanistically different anticancer agents was evaluated. MATERIALS AND METHODS: Eribulin was combined with cytotoxic agents (capecitabine, carboplatin, cisplatin, doxorubicin, gemcitabine) or targeted agents (bevacizumab, BKM-120, E7449, erlotinib, everolimus, lenvatinib, palbociclib) in tumor xenograft models of breast cancer, melanoma, non-small cell lung cancer (NSCLC), and ovarian cancer. RESULTS: Across nearly all models, eribulin with either cytotoxic or targeted agents demonstrated combination activity, defined as the activity demonstrably greater than that of either agent alone. Combination activity was absent only with doxorubicin (MDA-MB-435 model) and with lenvatinib (NCI-H1975 model), both of which responded to the agents as monotherapy. CONCLUSION: Eribulin has combination activity with multiple agents from different mechanistic classes in several human cancer models, including breast, NSCLC, ovarian, and melanoma. Copyright
BACKGROUND: Eribulin is used in many countries to treat patients with advanced breast cancer or liposarcoma and exerts in vivo anticancer activity under monotherapy conditions against various humantumor xenograft models. Here, eribulin in combination with mechanistically different anticancer agents was evaluated. MATERIALS AND METHODS: Eribulin was combined with cytotoxic agents (capecitabine, carboplatin, cisplatin, doxorubicin, gemcitabine) or targeted agents (bevacizumab, BKM-120, E7449, erlotinib, everolimus, lenvatinib, palbociclib) in tumor xenograft models of breast cancer, melanoma, non-small cell lung cancer (NSCLC), and ovarian cancer. RESULTS: Across nearly all models, eribulin with either cytotoxic or targeted agents demonstrated combination activity, defined as the activity demonstrably greater than that of either agent alone. Combination activity was absent only with doxorubicin (MDA-MB-435 model) and with lenvatinib (NCI-H1975 model), both of which responded to the agents as monotherapy. CONCLUSION: Eribulin has combination activity with multiple agents from different mechanistic classes in several humancancer models, including breast, NSCLC, ovarian, and melanoma. Copyright
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