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Phase II trial of imatinib mesylate in patients with metastatic melanoma

2008; Springer Nature; Volume: 99; Issue: 5 Linguagem: Inglês

10.1038/sj.bjc.6604482

1532-1827

KYOUNG‐MEE KIM, Omar Eton, Darren W. Davis, Marsha L. Frazier, David J. McConkey, A. Hafeez Diwan, Nicolas Papadopoulos, Agop Y. Bedikian, Luis H. Camacho, Merrick I. Ross, Janice N. Cormier, Jeffrey E. Gershenwald, J E Lee, Paul F. Mansfield, L. Billings, Chaan S. Ng, C Charnsangavej, Menashe Bar‐Eli, Marcella M. Johnson, Anthony J. Murgo, Víctor G. Prieto,

Sarcoma Diagnosis and Treatment

Metastatic melanoma cells express a number of protein tyrosine kinases (PTKs) that are considered to be targets for imatinib. We conducted a phase II trial of imatinib in patients with metastatic melanoma expressing at least one of these PTKs. Twenty-one patients whose tumours expressed at least one PTK (c-kit, platelet-derived growth factor receptors, c-abl, or abl-related gene) were treated with 400 mg of imatinib twice daily. One patient with metastatic acral lentiginous melanoma, containing the highest c-kit expression among all patients, had dramatic improvement on positron emission tomographic scan at 6 weeks and had a partial response lasting 12.8 months. The responder had a substantial increase in tumour and endothelial cell apoptosis at 2 weeks of treatment. Imatinib was fairly well tolerated: no patient required treatment discontinuation because of toxicity. Fatigue and oedema were the only grade 3 or 4 toxicities that occurred in more than 10% of the patients. Imatinib at the studied dose had minimal clinical efficacy as a single-agent therapy for metastatic melanoma. However, based on the characteristics of the responding tumour in our study, clinical activity of imatinib, specifically in patients with melanoma with certain c-kit aberrations, should be examined.