title: Tyrosine kinase inhibitor imatinib mesylate as anticancer agent for advanced ocular melanoma expressing immunoistochemical C-KIT (CD 117): preliminary results of a compassionate use clinical trial.
abstract: Imatinib mesylate (IM), is a selective and competitive inhibitor of tyrosine kinases, including BCR-ABL, ABL, KIT, and the platelet-derived growth factor receptors (PDGF-R). It binds to the ATP-binding site of the target kinase and prevents the transfer of phosphate from ATP to the tyrosine residues of various substrates. At oral doses of 200-600 mg, the majority of patients with chronic myeloid leukaemia, Philadelphia chromosome-positive acute lymphoblastic leukemia expressing the BCR-ABL fusion protein and gastrointestinal stromal tumours (GIST) achieve a bio-molecular and clinical response, frequently complete, associated with limited toxicity. Several other human cancers, as small-cell lung carcinoma, melanoma, seminoma, some sarcomas, and adenoid cystic carcinomas may over-express KIT or PDGF-R, and clinical trials to evaluate the role of IM in the treatment of such cancers are currently ongoing. We determined c-KIT with Dako CD 117 antibody in 5 cases of advanced ocular melanoma (OM) and we found positive immuno-reactivity for CD 117 in three patients. We treated all patients with palliative-use IM at the oral dose of 400 mgr daily. We obtained in expressing positive immuno-reactivity for CD 117 patients: a reduction of malignant ascites in one, a partial remission in the neck nodes in another, and progression of liver metastases in the third. Evidences of progression has been reported in the other two patients expressing negative immuno-reactivity for CD 117. We conclude that the effect of IM should be assessed only in OM with positive immuno-histochemical c-kit (CD 117) expression. IM might be a potential therapeutic strategy for these patients.
authors.affiliation: Department of Oncology , General City Hospital S. Giuseppe, Empoli, Italy. oncologiaempoli@usl11.toscana.it
authors.forename: G
authors.initials: G
authors.lastname: Fiorentini
authors.forename: S
authors.initials: S
authors.lastname: Rossi
authors.forename: G
authors.initials: G
authors.lastname: Lanzanova
authors.forename: M
authors.initials: M
authors.lastname: Biancalani
authors.forename: A
authors.initials: A
authors.lastname: Palomba
authors.forename: P
authors.initials: P
authors.lastname: Bernardeschi
authors.forename: P
authors.initials: P
authors.lastname: Dentico
authors.forename: U
authors.initials: U
authors.lastname: De Giorgi
mesh_terms: D000328:Adult; D001549:Benzamides; D014408:Biomarkers, Tumor / Q000032:analysis; D005134:Eye Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D007150:Immunohistochemistry; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D019009:Proto-Oncogene Proteins c-kit / Q000187:drug effects* / Q000378:metabolism; D011743:Pyrimidines / Q000627:therapeutic use*
chemical_list: D001549:Benzamides; D014408:Biomarkers, Tumor; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit