A multi-center phase II evaluation of the small molecule survivin suppressor YM155 in patients with unresectable stage III or IV melanoma

Karl D. Lewis, Wolfram Samlowski, John Ward, Joseph Catlett, Lee Cranmer, John Kirkwood, David Lawson, Eric Whitman, Rene Gonzalez

Research output: Contribution to journalArticle

103 Scopus citations

Abstract

Summary: Melanoma continues to be a major health problem with no effective therapy. Melanocytes, both benign and malignant, express many anti-apoptotic factors. Survivin is a member of the family of inhibitors of apoptosis proteins (IAP) and is preferentially expressed in tumor cells, including melanoma. YM155 is a small molecule suppressant of survivin that has been shown in preclinical cell lines, xenograft models and phase I studies to have anti-tumor activity. Methods: This was an open-label, multi-center, study of YM155 monotherapy in subjects with unresectable stage III or IV melanoma. Thirty-four chemotherapy naïve subjects were treated with YM155 at a dose of 4.8 mg/m 2/day administered by continuous infusion for 168-hours (7 days) followed by a 14-day rest period, for up to 6 cycles or until disease progression. Results: One subject had a partial response to treatment seen at cycle two and lasting through cycle eight. Median progression-free survival was 1.3 months (95% CI; 1.3-2.7). Median overall survival was 9.9 months (95% CI; 7.0-14.5). Overall, YM155 was well tolerated with the most common (>20%) adverse events reported as fatigue, nausea, pyrexia, headache, arthralgia and back pain. Only four subjects required dose reductions. Conclusions: YM155 was well tolerated in subjects with advanced melanoma; however, the pre-specified primary end-point for efficacy which required two responders in 29 evaluable subjects was not achieved.

Original languageEnglish (US)
Pages (from-to)161-166
Number of pages6
JournalInvestigational New Drugs
Volume29
Issue number1
DOIs
StatePublished - Feb 1 2011

Keywords

  • Melanoma
  • Survivin
  • YM155

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'A multi-center phase II evaluation of the small molecule survivin suppressor YM155 in patients with unresectable stage III or IV melanoma'. Together they form a unique fingerprint.

  • Cite this