1. ¹Department of Melanoma Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
2. ²ApoCell Inc., Houston, TX, USA
3. ³Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
4. ⁴Department of Cancer Biology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
5. ⁵Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
6. ⁶Department of Diagnostic Radiology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
7. ⁷Department of Biostatistics and Applied Mathematics, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
8. ⁸The Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD, USA

Correspondence: Dr O Eton, Department of Melanoma Medical Oncology, Unit 430, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. E-mail: Omar.Eton@mpi.com

Received 3 December 2007; Revised 4 June 2008; Accepted 10 June 2008; Published online 19 August 2008.

Abstract

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.