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Antitumor activity of irofulven monotherapy and in combination with mitoxantrone or docetaxel against human prostate cancer models
Author(s) -
Van Laar Emily S.,
Weitman Steven,
MacDonald John R.,
Waters Stephen J.
Publication year - 2003
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.10351
Subject(s) - mitoxantrone , docetaxel , prostate cancer , medicine , prostate , cancer , antimetabolite , in vivo , pharmacology , oncology , cancer research , chemotherapy , biology , microbiology and biotechnology
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. © 2003 Wiley‐Liss, Inc.