Bortezomib: efficacy comparisons in solid tumors and hematologic malignancies

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Abstract
Bortezomib is a protease inhibitor and is the first compound in this drug class to be used in clinical practice, with trials demonstrating efficacy in patients with relapsed/refractory multiple myeloma. Mature clinical data on the efficacy of bortezomib in solid tumors are not yet available, but early clinical data indicate this could be a promising drug for the treatment of advanced solid tumors. This Review summarizes the principal clinical trials of bortezomib and discusses its efficacy in solid and hematologic tumors. Proteasome inhibition represents a new anticancer approach, with the potential effect of arresting tumor growth, metastasis and angiogenesis through the activation of multiple mechanisms. Bortezomib is a biologically active agent, producing predictable, dose-related and reversible proteasome inhibition; it has shown antitumor activity in various malignancies and is the first proteasome inhibitor to be used in clinical practice. Several trials demonstrated that bortezomib is relatively well tolerated, causing manageable nonhematologic and hematologic toxicity. The drug was approved in 2003 by the FDA for the treatment of patients with multiple myeloma who had received at least two prior therapies and demonstrated disease progression on the last therapy; its application was expanded recently for second-line treatment. This article summarizes the principal clinical trials of bortezomib and discusses its efficacy in solid and hematologic tumors.