Optimizing and predicting the in vivo activity of AT9283 as a monotherapy and in combination with paclitaxel

Journal of Gastrointestinal Cancer
Emad Y Moawad

Abstract

This study aims in optimizing and predicting the in-vivo activity of AT9283 as a monotherapy and evaluating its combination with paclitaxel. The effectiveness of AT9283 was examined in several mouse models engrafted with BCR-ABL(+) leukemic, human multiple myeloma (MM), and human colorectal carcinoma (HCT116) cells. Dose modeling was performed by analyzing previously published data of AT9283 cancer growth inhibition in vivo. The effects of 2 cycles (7.5-12.5 mg/kg AT9283 twice daily, 5 days/week), 4 cycles (45 mg/kg AT9283 once daily, twice/week), and 3 cycles (10 mg/kg AT9283 twice daily for 5 days or 12.5 mg/kg paclitaxel once/week followed by 5 mg/kg AT9283 twice daily for 4 days) on xenograft growth were quantified to identify the energy yield associated with the different doses. The continuous infusion regimens (5 days/week) used in the mice engrafted with BCR-ABL+ cells were more efficient than the regimens with twice weekly drug administration used in the mice engrafted with MM cells. The energy yield of the treatment regimen used in the BCR-ABL(+) model was perfectly correlated (r = 1) with the AT9283 dose logarithm. An efficient dose-energy model with a perfect fit (R (2) = 1) estimating the energy yield achieved by th...Continue Reading

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Apr 4, 2017·Expert Opinion on Therapeutic Patents·Daniel PlanoArun K Sharma

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