21 april 2005: Bron: British Journal of Cancer (2005) 92, 1398-1405. doi:10.1038/sj.bjc.6602529

Gleevec - Imatinib geeft geen enkel positief effect bij kleine groep van melanoompatiënten (18) met uitzaaiïngen, blijkt uit kleinschalige fase II trial uitgevoerd in twee Duitse ziekenhuizen.

Lack of clinical efficacy of imatinib in metastatic melanoma

S Ugurel1, R Hildenbrand2, A Zimpfer1, P La Rosée3, P Paschka3, A Sucker1, P Keikavoussi4, J C Becker4, W Rittgen5, A Hochhaus3 and D Schadendorf1
1Skin Cancer Unit, German Cancer Research Center Heidelberg and Department of Dermatology, University Hospital of Mannheim, Theodor-Kutzer-Ufer 1, D-68167 Mannheim, Germany
2Department of Pathology, University Hospital of Mannheim, 68167 Mannheim, Germany
3III. Medizinische Klinik, Fakultät für Klinische Medizin Mannheim der Universität Heidelberg, 68167 Mannheim, Germany
4Department of Dermatology, University Hospital of Würzburg, 97080 Würzburg, Germany
5Central Unit of Biostatistics, German Cancer Research Center, 69120 Heidelberg, Germany

Correspondence to: Dr S Ugurel, E-mail: s.ugurel@dkfz.de

Received 1 January 2005; revised 23 February 2005; accepted 23 February 2005

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-R and -R 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-R in seven out of 12 cases (58%) and for PDGF-R 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.

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