Figure 5.

In vivo antitumor activity of single-agent BMS-754807, letrozole, tamoxifen, or in combinations. Ovariectomized female nu/nu mice between the ages of 7 to 8 weeks old were inoculated with MCF-7/AC-1 tumor cells in each flank with supplemental androstenedione (100 μg/d). Once the bilateral flank tumors grew such that the average of their left and right tumor volumes are between 250 to 300 mm³, mice were randomized to each treatment group and given various treatments for a total of 28 days; treatment groups consisted of 8 to 10 mice per group, and the experiments were repeated 3 times. The tumor volumes were measured twice weekly. At day 28, the average of the left and right tumor volumes of each mouse and percent change from its pretreatment average volume was determined, then 1 of the 2 flank tumors was surgically excised from each tumor-bearing animal. Animals were then observed until study endpoint. Tumor volume was measured at the intervals indicated and expressed as percentage change in tumor volume relative to start of treatment (baseline, day 0). A and B, at the end of study treatment, both the combination of letrozole + BMS-754807 and tamoxifen + BMS-754807 had significantly improved antitumor activity compared with the respective single agents. (bilateral tumor measurements). Points, mean; bars, SE. C and D, time to endpoint following treatment with BMS-754807 and/or hormonal therapy (single remnant tumor measurements). Points, mean; bars, SE.