Matrix metalloproteinase inhibitors (MMPIs): the beginning of phase I or the termination of phase III clinical trials

Cancer Metastasis Reviews
Maria Pavlaki, S Zucker

Abstract

The decade of the 1990s was ripe with enthusiasm for the use of MMPIs to treat cancer. Limitations to new cytotoxic chemotherapy approaches to treat solid cancers and a better understanding of tumor biology provided a strong impetus for alternative drug development. It is estimated that the pharmaceutical industry invested at least a billion dollars in this effort. Because MMPIs represent an entirely different therapeutic modality from proven anti-cancer agents, many of the therapeutic trials designed to test MMPIs in human patients with cancer bypassed traditional approaches to evaluate drug efficiency. The concept of systematic progression from small phase I (dose escalation to toxicity to examine drug safety), to phase II (drug treatment of patients with cancer types considered to be good candidates for the selected drug), to phase III (randomized trial of new drug versus best available therapy to determine drug efficacy) trials was modified. Much to the chagrin of everyone involved in these studies, the randomized trials of MMPIs in advanced cancer have, pretty much, flopped. This review article will attempt to dissect out aspects of previous human and animal studies that may be helpful in making decisions about the future ...Continue Reading

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