Problem #1 - Getting that past your IACUC. You'd be hard pressed to convince an IACUC committee to allow establishment of multiple xenograft tumors in a single mouse. Some don't even allow bilateral footpad injections w/o a special exemption.

Beyond this regulatory issue, I don't know that it's particularly practical. Different cell lines produce tumors at different rates and will probably be affected differently by your compound--even if they are derived from the same cancer type. You have to sac the animal once the tumor reaches a certain size, but if you're injecting 2 different lines in same mouse, then you'll likely have to sac the mouse before one of the tumors reaches the endpoint. You're much better off using a single line per mouse. In the long run, you probably won't be using anymore mice for the experiment than you would putting 2 xenografts into the one mouse.