Multicenter phase II trial of high-dose imatinib mesylate in metastatic melanoma: Significant toxicity with no clinical efficacy

Ken Wyman, Michael B. Atkins, Victor Prieto, Omar Eton, David F. McDermott, Francie Hubbard, Christine Byrnes, Kathleen Sanders, Jeffrey A. Sosman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

223 Scopus citations

Abstract

BACKGROUND. Systemic treatment of metastatic melanoma is largely ineffective and alternative approaches are needed. Imatinib mesylate is an oral tyrosine kinase inhibitor that targets bcr-Abl, c-kit, platelet-derived growth factor receptor (PDGFR)-α, and PDGFR-β, leading to remarkable clinical responses in several cancers. Signal transduction via c-kit, PDGFR-α, and PDGFR-β has been demon-strated in malignant melanoma. METHODS. The primary objective of this Phase II study was to determine the response rate, response duration, and the frequency of 6-month progression-free survival in patients who could receive up to 2 prior therapeutic regimens. Initially, patients received imatinib at at dose of 400 mg twice orally each day. Based on Simon's optimal design, the study allowed entry of 21 patients; if there were a 2 objective responses, accrual would then continue to a total of 41 patients. RESULTS. Twenty-six patients were enrolled. Patients experienced 29 episodes of Grade 3 and 2 episodes of Grade 4 toxicity (according to National Cancer Institute common toxicity criteria). No objective clinical responses were noted among the 25 evaluable patients. The median time to progression was 54 days and the median overall survival was 200 days. No patient was free of disease progression at 6 months. Paraffin-embedded tumor specimens from 15 patients were tested for expression of imatinib responsive kinases by immunohistochemistry. Three tumors had moderate and 5 tumors had weak staining for c-kit. Five tumor samples had weak staining for PDGFR-α and -β. CONCLUSIONS. Imatinib is an inactive single agent in metastatic melanoma in a population of predominately pretreated patients. The levels of c-kit and/or PDGFR-α, -β expression in the current study were lower than previously reported. Alternative treatment strategies remain a priority for patients with advanced melanoma.

Original languageEnglish (US)
Pages (from-to)2005-2011
Number of pages7
JournalCancer
Volume106
Issue number9
DOIs
StatePublished - May 1 2006

Keywords

  • Clinical trial
  • Imatinib
  • Metastatic melanoma
  • Phase II
  • Targeted therapy
  • Tyrosine kinase inhibitor

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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