Phase I dose-escalation study of the novel antiandrogen BMS-641988 in patients with castration-resistant prostate cancer

Dana Rathkopf, Glenn Liu, Michael A. Carducci, Mario A. Eisenberger, Aseem Anand, Michael J. Morris, Susan F. Slovin, Yasutsuna Sasaki, Shunji Takahashi, Seiichiro Ozono, Nga Kit Eliza Fung, Shinta Cheng, Jinping Gan, Marco Gottardis, Mary T. Obermeier, Jyotsna Reddy, Steven Zhang, Blisse J. Vakkalagadda, Leila Alland, George WildingHoward I. Scher

Research output: Contribution to journalArticlepeer-review


Purpose: BMS-641988 is an androgen receptor antagonist with increased potency relative to bicalutamide in both in vitro and in vivo prostate cancer models. A first-in-man phase I study was conducted to define the safety and tolerability of oral BMS-641988 in patients with castration-resistant prostate cancer (CRPC). Experimental Design: Doses were escalated from 5 to 150 mg based on discrete pharmacokinetic parameters in cohorts of three to six subjects. After establishing safety with 20 mg of BMS-641988 in the United States, a companion study was opened in Japan to assess differences in drug metabolism between populations. Results: Sixty-one men with CRPC were treated with daily BMS-641988. The pharmacokinetics (PK) of BMS-641988 and its active metabolites were proportional to dose. One patient experienced an epileptic seizure at a dose of 60 mg administered twice. Despite achieving target drug exposures, antitumor activity was limited to one partial response. Seventeen of 23 evaluable patients (74%) exhibited stable disease on imaging (median 15 weeks; range 8-32), and 10 of 61 patients (16%) achieved a ≥30% decline in levels of prostate-specific antigen (PSA). Partial agonism was seen within the context of this study upon removal of the drug as evidenced by a decrease in PSA. Conclusions: Although the clinical outcomes of predominantly stable disease and partial agonism were similar to what was observed in the preclinical evaluation of the compound, the limited antitumor activity of BMS-641988 at therapeutic dose levels coupled with an episode of seizure activity led to study closure.

Original languageEnglish (US)
Pages (from-to)880-887
Number of pages8
JournalClinical Cancer Research
Issue number4
StatePublished - Feb 15 2011

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


Dive into the research topics of 'Phase I dose-escalation study of the novel antiandrogen BMS-641988 in patients with castration-resistant prostate cancer'. Together they form a unique fingerprint.

Cite this