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

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 1 2011

Fingerprint

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

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pharmacology
  • Pharmacology (medical)

Cite this

Lewis, Karl D. ; Samlowski, Wolfram ; Ward, John ; Catlett, Joseph ; Cranmer, Lee ; 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.
@article{e98c0196f31a42cda8fa362db3561a3f,
title = "A multi-center phase II evaluation of the small molecule survivin suppressor YM155 in patients with unresectable stage III or IV melanoma",
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 na{\"i}ve 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.",
author = "Lewis, {Karl D.} and Wolfram Samlowski and John Ward and Joseph Catlett and Lee Cranmer and John Kirkwood and David Lawson and Eric Whitman and Rene Gonzalez",
year = "2011",
month = "2",
day = "1",
doi = "10.1007/s10637-009-9333-6",
language = "English (US)",
volume = "29",
pages = "161--166",
journal = "Investigational New Drugs",
issn = "0167-6997",
publisher = "Kluwer Academic Publishers",
number = "1",

}

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; Kirkwood, John; Lawson, David; Whitman, Eric; Gonzalez, Rene.

In: Investigational New Drugs, Vol. 29, No. 1, 01.02.2011, p. 161-166.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A multi-center phase II evaluation of the small molecule survivin suppressor YM155 in patients with unresectable stage III or IV melanoma

AU - Lewis, Karl D.

AU - Samlowski, Wolfram

AU - Ward, John

AU - Catlett, Joseph

AU - Cranmer, Lee

AU - Kirkwood, John

AU - Lawson, David

AU - Whitman, Eric

AU - Gonzalez, Rene

PY - 2011/2/1

Y1 - 2011/2/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=79151481416&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79151481416&partnerID=8YFLogxK

U2 - 10.1007/s10637-009-9333-6

DO - 10.1007/s10637-009-9333-6

M3 - Article

VL - 29

SP - 161

EP - 166

JO - Investigational New Drugs

JF - Investigational New Drugs

SN - 0167-6997

IS - 1

ER -