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Bortezomib: efficacy comparisons in solid tumors and hematologic malignancies

Nature Clinical Practice Oncology volume 3, pages 374–387 (2006)Cite this article

Abstract

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.

Key Points

  • Bortezomib positively regulates the expression of many proapoptotic proteins and downregulates the transcription of proteins that promote cell growth and survival

  • Bortezomib enhances the anticancer effects of radiation therapy, immunotherapy and novel agents

  • A phase III trial demonstrated the superior efficacy of bortezomib compared with dexamethasone in patients with relapsed multiple myeloma

  • Several clinical trials of patients with refractory multiple myeloma showed that bortezomib is relatively well tolerated with manageable side effects

  • Phase I and II trial data demonstrated partial response efficacy of bortezomib in various solid tumors; this drug shows promise as a new potential anticancer approach

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Figure 1: Bortezomib targets not only malignant myeloma cells but also their microenvironment, including cytokine regulation, angiogenesis inhibition and alteration of the adherence of malignant myeloma cells to extracellular matrix proteins and bone marrow stromal cells.

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Authors and Affiliations

  1. Chief of the Myeloma Unit in the Hematology Department of St Eugenio Hospital, Rome, Italy

    Tommaso Caravita

  2. Associate Professor of Hematology at University Tor Vergata, and Chief of Hematology at the St Eugenio Hospital, both in Rome,

    Paolo de Fabritiis

  3. Director of the Hematology Department, University Tor Vergata,

    Sergio Amadori

  4. Chief of the Myeloma Unit in the Department of Oncology,

    Antonio Palumbo

  5. Director of the Hematology Department, University of Torino, Italy

    Mario Boccadoro

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  1. Tommaso Caravita
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Correspondence to Tommaso Caravita.

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Bortezomib is a protease inhibitor and is the first compound in this drug class to be used in clinical practice, with clinical trials showing demonstrated 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.

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Caravita, T., de Fabritiis, P., Palumbo, A. et al. Bortezomib: efficacy comparisons in solid tumors and hematologic malignancies. Nat Rev Clin Oncol 3, 374–387 (2006). https://doi.org/10.1038/ncponc0555

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