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Changes in Prostate-Specific Antigen (PSA) Level Correlate with Growth Inhibition of Prostate Cancer Cells Treated in Vitro with a Novel Anticancer Drug, Irofulven

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Abstract

Irofulven (hydroxymethylacylfulvene,HMAF, MGI 114) is a novel agent withalkylating activity and a potent inducer ofapoptosis. It is currently undergoing PhaseII clinical trials for several tumor types,including hormone-refractory prostatecancer. Reduction of serumprostate-specific antigen (PSA) levels hasbeen proposed as a generally usefulendpoint for evaluating the antitumorefficacy of treatments for prostate cancer.However, the utility of PSA as a marker oftumor cell burden could be compromised, ifdrugs directly affected PSA secretionand/or expression. In these studies, weevaluated the effects of irofulven on PSAprotein and mRNA levels during the courseof treatment of prostate tumor cells in vitro. Therate of PSA secretion(normalized per equal cell number) bycontrol and drug treated cells was similar,as determined by a solid phase, two-siteimmunoradiometric assay. Consistent withthe lack of effect of irofulven on PSAprotein level, the drug does not appear toaffect the expression of PSA mRNA (on a percell basis) as assessed by RT-PCR. Thus,changes in PSA secretion and expressionappear to reflect irofulven-induced cellgrowth inhibition rather than reflecting adirect effect of the drug on PSA. Theseresults suggest that PSA should be areasonable marker of tumor burden inirofulven-treated prostate cancerpatients.

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Authors and Affiliations

  1. Department of Radiation Oncology, The University of Texas Health Science Center, San Antonio, TX

    Barbara A. Woynarowska, Arlene L. Higdon, Ruben M. Muñoz, Perry Bushong & Stephen J. Waters

  2. MGI Pharma, Inc., Bloomington, MN, U.S.A.

    Barbara A. Woynarowska, Arlene L. Higdon, Ruben M. Muñoz & Stephen J. Waters

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  1. Barbara A. Woynarowska
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Woynarowska, B.A., Higdon, A.L., Muñoz, R.M. et al. Changes in Prostate-Specific Antigen (PSA) Level Correlate with Growth Inhibition of Prostate Cancer Cells Treated in Vitro with a Novel Anticancer Drug, Irofulven. Invest New Drugs 19, 283–291 (2001). https://doi.org/10.1023/A:1010601524630

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