Antitumor activity of irofulven monotherapy and in combination with mitoxantrone or docetaxel against human prostate cancer models.

BACKGROUND: Irofulven (6-hydroxymethylacylfulvene, HMAF, MGI 114) is a novel antitumor agent currently undergoing clinical trials in hormone-refractory prostate cancer. This report examines the efficacy of irofulven alone or in combination with mitoxantrone or docetaxel against androgen-independent prostate cancer cell lines.
METHODS: To elucidate the activity of irofulven monotherapy and in combination, PC-3 and DU-145 cell lines were utilized in cellular viability assessments and tumor growth inhibition studies.
RESULTS: Viability assays with irofulven and mitoxantrone show additive to synergistic activity. Furthermore, irofulven and mitoxantrone in combination exhibit enhanced antitumor activity against PC-3 and DU-145 xenografts. Additive combination effects are also observed when irofulven and docetaxel were tested against PC-3 xenografts and curative activity (8/10 CR) is observed in DU-145 xenografts.
CONCLUSIONS: These studies demonstrate that irofulven displays strong activity as monotherapy and in combination with mitoxantrone or docetaxel against androgen-independent prostate cancer in vitro and in vivo; thus, supporting the clinical investigation of irofulven against hormone-refractory prostate cancer. Copyright 2003 Wiley-Liss, Inc.