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 D Cranmer, John Kirkwood, David Lawson, Eric Whitman, Rene Gonzalez

Research output: Contribution to journalArticle

99 Citations (Scopus)

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 2011

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Melanoma
Inhibitor of Apoptosis Proteins
Melanocytes
Arthralgia
Back Pain
Heterografts
Nausea
Disease-Free Survival
Fatigue
Headache
Disease Progression
Neoplasms
Fever
Drug Therapy
Cell Line
Survival
Health
Therapeutics

Keywords

  • Melanoma
  • Survivin
  • YM155

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Oncology

Cite this

A multi-center phase II evaluation of the small molecule survivin suppressor YM155 in patients with unresectable stage III or IV melanoma. / Lewis, Karl D.; Samlowski, Wolfram; Ward, John; Catlett, Joseph; Cranmer, Lee D; Kirkwood, John; Lawson, David; Whitman, Eric; Gonzalez, Rene.

In: Investigational New Drugs, Vol. 29, No. 1, 02.2011, p. 161-166.

Research output: Contribution to journalArticle

Lewis, Karl D. ; Samlowski, Wolfram ; Ward, John ; Catlett, Joseph ; Cranmer, Lee D ; Kirkwood, John ; Lawson, David ; Whitman, Eric ; Gonzalez, Rene. / A multi-center phase II evaluation of the small molecule survivin suppressor YM155 in patients with unresectable stage III or IV melanoma. In: Investigational New Drugs. 2011 ; Vol. 29, No. 1. pp. 161-166.
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