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

Autor: John Harris Ward, John M. Kirkwood, Eric Whitman, Karl D. Lewis, David H. Lawson, Lee D. Cranmer, Joseph P. Catlett, Rene Gonzalez, Wolfram E. Samlowski
Rok vydání: 2009
Předmět:
Zdroj: Investigational New Drugs. 29:161-166
ISSN: 1573-0646
0167-6997
DOI: 10.1007/s10637-009-9333-6
Popis: 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 naive subjects were treated with YM155 at a dose of 4.8 mg/m2/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.
Databáze: OpenAIRE
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