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SHR Neuro Cancer Cardio Lipid Metab Microb

Ugurel, S; Hildenbrand, R; Zimpfer, A; La Rosee, P; Paschka, P; Sucker, A; Keikavoussi, P; Becker, JC; Rittgen, W; Hochhaus, A; Schadendorf, D.
Lack of clinical efficacy of imatinib in metastatic melanoma.
Br J Cancer. 2005; 92(8):1398-1405 Doi: 10.1038/sj.bjc.6602529 [OPEN ACCESS]
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Leading authors Med Uni Graz: Ugurel-Becker Selma
Co-authors Med Uni Graz: Becker Jürgen Christian
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Abstract:: This two-centre phase-II trial aimed at investigating the efficacy of imatinib in metastasised melanoma patients in correlation to the tumour expression profile of the imatinib targets c-kit and platelet-derived growth factor receptor (PDGF-R). The primary study end point was objective response according to RECIST, secondary end points were safety, overall and progression-free survival. In all, 18 patients with treatment-refractory advanced melanoma received imatinib 800 mg day(-1). In 16 evaluable patients no objective responses could be observed. The median overall survival was 3.9 months, the median time to progression was 1.9 months. Tumour biopsy specimens were obtained from 12 patients prior to imatinib therapy and analysed for c-kit, PDGF-Ralpha and -Rbeta expression by immunohistochemistry. In four cases, cell lines established from these tumour specimens were tested for the antiproliferative effects of imatinib and for functional mutations of genes encoding the imatinib target molecules. The tumour specimens stained positive for CD117/c-kit in nine out of 12 cases (75%), for PDGF-Ralpha in seven out of 12 cases (58%) and for PDGF-Rbeta in eight out of 12 cases (67%). The melanoma cell lines showed a heterogenous expression of the imatinib target molecules without functional mutations in the corresponding amino-acid sequences. In vitro imatinib treatment of the cell lines showed no antiproliferative effect. In conclusion, this study did not reveal an efficacy of imatinib in advanced metastatic melanoma, regardless of the expression pattern of the imatinib target molecules c-kit and PDGF-R.
Find related publications in this database (using NLM MeSH Indexing): Adult -; Aged -; Antineoplastic Agents - therapeutic use; Base Sequence -; Cell Line, Tumor -; Cell Proliferation - drug effects; DNA Mutational Analysis -; Female -; Humans -; Immunohistochemistry -; Male -; Melanoma - drug therapy Melanoma - mortality; Middle Aged -; Molecular Sequence Data -; Neoplasm Metastasis - drug therapy; Piperazines - therapeutic use; Proto-Oncogene Proteins c-kit - drug effects Proto-Oncogene Proteins c-kit - genetics Proto-Oncogene Proteins c-kit - metabolism; Pyrimidines - therapeutic use; Receptors, Platelet-Derived Growth Factor - drug effects Receptors, Platelet-Derived Growth Factor - genetics Receptors, Platelet-Derived Growth Factor - metabolism; Reverse Transcriptase Polymerase Chain Reaction -; Treatment Outcome -
Find related publications in this database (Keywords): imatinib; melanoma; c-kit; PDGF-R