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A phase II and pharmacological study of the matrix metalloproteinase inhibitor (MMPI) COL-3 in patients with advanced soft tissue sarcomas

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An Erratum to this article was published on 13 April 2007

Summary

This phase II study evaluated the antitumor activity of the tetracycline analog COL-3, a potent inhibitor of metalloproteinases (MMPs), particularly MMP-2 and MMP-9, on a continuous oral schedule at a dose of 50 mg/m2 daily in patients with advanced and/or metastatic soft tissue sarcoma (STS). The principal endpoints were the rate of objective tumor regression and the proportion of patients who did not experience disease progression during the first 8 weeks of treatment. Other study objectives included an assessment of pharmacology of COL-3, time to progression (TTP), and overall survival. A Simon two-stage design with multinomial stop** rule was employed, with 15 patients enrolled during the first stage of the study. Although COL-3 was generally well-tolerated, there were no objective responses and 5(33%) patients experienced disease progression during the first 8 weeks of treatment, which exceeded the criteria established a priori with regard to pursuing further evaluations of COL-3 in STS. The median values for TTP and survival were 109 and 279 days, respectively. Based on these results, further studies of COL-3 on this administration schedule in patients with STS are not warranted.

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Abbreviations

MMP:

Metalloproteinase

TTP:

Time to progression

MMPI:

Metalloproteinase inhibitor

STS:

Soft tissue sarcomas

ECOG:

Eastern Cooperative Group

CT:

Computerized tomography

RECIST:

Response evaluation criteria in solid tumours

HPLC:

High-performance liquid chromatography

SD:

Stable disease

PR:

Partial response

CR:

Complete response

HIV:

Human Immunodeficiency Virus

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Acknowledgments

The study was supported by a unrestricted grant from CollaGenex (Newton, PA).

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Authors and Affiliations

  1. Cross Cancer Institute, 11560 University Avenue, Edmonton, AB T6G 1Z2, Canada

    Quincy S. C. Chu

  2. Institute for Drug Development, Cancer Therapy and Research Center, University of Texas Health Science Center, San Antonio, TX, USA

    Bahram Forouzesh, Samira Syed, Monica Mita, Joshua Copper, Janet Curtright & Eric K. Rowinsky

  3. Brooke Army Medical Center, Fort Sam Houston, TX, USA

    Garry Schwartz

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  1. Quincy S. C. Chu
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  2. Bahram Forouzesh
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Correspondence to Quincy S. C. Chu.

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An erratum to this article can be found at http://dx.doi.org/10.1007/s10637-007-9047-6

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Chu, Q.S.C., Forouzesh, B., Syed, S. et al. A phase II and pharmacological study of the matrix metalloproteinase inhibitor (MMPI) COL-3 in patients with advanced soft tissue sarcomas. Invest New Drugs 25, 359–367 (2007). https://doi.org/10.1007/s10637-006-9031-6

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