Clinical responses observed with imatinib or sorafenib in melanoma patients expressing mutations in KIT - PubMed (original) (raw)

Case Reports

. 2010 Apr 13;102(8):1219-23.

doi: 10.1038/sj.bjc.6605635. Epub 2010 Apr 6.

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Case Reports

Clinical responses observed with imatinib or sorafenib in melanoma patients expressing mutations in KIT

D Handolias et al. Br J Cancer. 2010.

Abstract

Background: Mutations in KIT are more frequent in specific melanoma subtypes, and response to KIT inhibition is likely to depend on the identified mutation.

Methods: A total of 32 patients with metastatic acral or mucosal melanoma were screened for mutations in KIT exons 11, 13 and 17.

Results: KIT mutations were found in 38% of mucosal and in 6% of acral melanomas. Three patients were treated with imatinib and one with sorafenib. All four patients responded to treatment, but three have since progressed within the brain.

Conclusion: The observed clinical responses support further investigation of KIT inhibitors in metastatic melanoma, selected according to KIT mutation status.

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Figures

Figure 1

Figure 1

CT chest images of pulmonary metastasis arising from anal melanoma at baseline (A) and then at 3 months (B) showing reduction in the size of the lesion on imatinib (Case 1).

Figure 2

Figure 2

CT pelvis and FDG PET/CT images at baseline (A, B) and at 1 month (C, D) after treatment of a metastatic vulval melanoma with imatinib. Arrows indicate areas of response (Case 2).

Figure 3

Figure 3

Marked LDH response within 2 weeks of commencing imatinib in a metastatic mucosal melanoma arising from the labia (Case 3). Dashed line indicates upper limit of the reference range.

Figure 4

Figure 4

Chest X-ray and chest CT images at baseline (A, B) and then at 1 month (C, D) after treatment of a metastatic anal melanoma with sorafenib demonstrates significant reduction in the number and size of pulmonary metastases. Arrows indicate major sites of response (Case 4).

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References

    1. Altintas A, Cil T, Kilinc I, Kaplan MA, Ayyildiz O (2007) Central nervous system blastic crisis in chronic myeloid leukemia on imatinib mesylate therapy: a case report. J Neurooncol 84: 103–105 - PubMed
    1. Antonescu CR, Busam KJ, Francone TD, Wong GC, Guo T, Agaram NP, Besmer P, Jungbluth A, Gimbel M, Chen CT, Veach D, Clarkson BD, Paty PB, Weiser MR (2007) L576P KIT mutation in anal melanomas correlates with KIT protein expression and is sensitive to specific kinase inhibition. Int J Cancer 121: 257–264 - PubMed
    1. Beadling C, Jacobson-Dunlop E, Hodi FS, Le C, Warrick A, Patterson J, Town A, Harlow A, Cruz III F, Azar S, Rubin BP, Muller S, West R, Heinrich MC, Corless CL (2008) KIT gene mutations and copy number in melanoma subtypes. Clin Cancer Res 14: 6821–6828 - PubMed
    1. Breedveld P, Pluim D, Cipriani G, Wielinga P, van Tellingen O, Schinkel AH, Schellens JH (2005) The effect of Bcrp1 (Abcg2) on the in vivo pharmacokinetics and brain penetration of imatinib mesylate (Gleevec): implications for the use of breast cancer resistance protein and P-glycoprotein inhibitors to enable the brain penetration of imatinib in patients. Cancer Res 65: 2577–2582 - PubMed
    1. Curtin JA, Busam K, Pinkel D, Bastian BC (2006) Somatic activation of KIT in distinct subtypes of melanoma. J Clin Oncol 24: 4340–4346 - PubMed

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