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Multicenter Phase II trial of high-dose imatinib mesylate in metastatic melanoma†
Significant toxicity with no clinical efficacy
Article first published online: 24 MAR 2006
Copyright © 2006 American Cancer Society
Volume 106, Issue 9, pages 2005–2011, 1 May 2006
How to Cite
Wyman, K., Atkins, M. B., Prieto, V., Eton, O., McDermott, D. F., Hubbard, F., Byrnes, C., Sanders, K. and Sosman, J. A. (2006), Multicenter Phase II trial of high-dose imatinib mesylate in metastatic melanoma. Cancer, 106: 2005–2011. doi: 10.1002/cncr.21834
Presented in part as a poster (abstract 2865) at the Annual Meeting of the American Society of Clinical Oncology; Chicago, Illinois, May 31–June 3, 2003.
- Issue published online: 18 APR 2006
- Article first published online: 24 MAR 2006
- Manuscript Accepted: 29 NOV 2005
- Manuscript Revised: 7 NOV 2005
- Manuscript Received: 8 SEP 2005
- Novartis Pharmaceutical. Grant Number: 5K24CA97588-3
- metastatic melanoma;
- targeted therapy;
- tyrosine kinase inhibitor;
- phase II;
- clinical trial
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 demonstrated in malignant melanoma.
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 ≥ 2 objective responses, accrual would then continue to a total of 41 patients.
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.
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. Cancer 2006. © 2006 American Cancer Society.