This protocol will evaluate the safety and pharmacokinetics of paclitaxel and BAY 12-9556. The latter is a novel, non-peptidic biphenyl matrix metalloproteinase (MMP) inhibitor. The breaching of the extracellular matrix is believed to be important in local invasion of tumors and in tumor metastases. Interference with the activity of MMPs has been shown to inhibit invasion in vitro and in vivo and can block tumor-induced neovascularization. Paclitaxel is known to be cytotoxic and to have well-defined short and long term toxicities. It is hypothesized that it is safe to administer a fixed dose of BAY 12-9556 while increasing the dose of paclitaxel gradually; that the synergistic activity of the two drugs in combination will create greater efficacy in tumor destruction through blocking angiogenesis.
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