For further activities T everolimus recording a second cohort with a h was Heren dose were treated. A mediator Nalysis of the second cohort, the median PFS and OS was found a little less than 2 months and Roscovitine 9.5 months respectively tempering of enthusiasm by the T Activity generated in the first cohort. Of the 53 patients included had a total, two patients best PR CONFIRMS. The authors concluded that everolimus monotherapy had an underactive patients with metastatic melanoma. The reason why patients were treated with the lower dose had a L Ngere survival time as compared to those treated with high doses, is unknown. c KIT inhibitors increased three trade obtained by orally administered small molecule tyrosine kinase inhibitors imatinib, dasatinib, nilotinib, and are evaluated in melanoma. Although the three agents inhibit c KIT, PDGFR, BCR-ABL, and they differ in their potency in inhibiting the cellular Re recording, interaction with kinase mechanism and inhibition profile throughout kinases.
67 other cellular Were re 93.94 The three drugs initially Highest for the treatment of patients with myeloid leukemia mie approved chronicle of the translocation product BCR ABL.95 97 times imatinib and dasatinib activity GIST have CI-1033 shown t with u only activating mutations of the KIT or C PDGFR.98, 99 The results suggest that this agent k can call a activity t of c-kit gene and m possibly the amplified c KIT have melanoma. Imatinib mesylate Five phase II studies have been conducted with imatinib as a single agent and the results of these tests show the importance of the selection of patients based on the presence of mutations in 104 tumors.
100 In three studies in the nonchronically Most patients with melanoma sun and dam unnecessary damaged KIT mutation c for inclusion, was only one of 65 patients with RA, and the patient ac KIT mutation positive acral melanoma.102 104 In contrast, two studies Phase II melanoma patients as needed ver ffentlicht accommodate Mutations of KIT with c reported radically different results.100, 101 were by these two studies, there are two CRs and 14 PRs under 65 evaluable patients what. a response rate of almost 25% Responses were observed in melanomas with KIT mutations c with known functional relevance. KIT mutations in exons 11 and 13 c seems to better reflect the answer is c-KIT expression evaluated immunohistochemistry.67 details or confirmation These promising results with imatinib in this subgroup of patients with melanoma molecular warrant Best A prospective randomized study.
Dasatinib, a phase II study in an unselected population of patients with advanced melanoma molecular recently was published.105 Of the 36 patients evaluable for response, two had a PR lasting 24 weeks or more. One of these patients, it was found that approximately KIT mutation. The other speaker was a wild-type c-KIT gene, but amplification of c-kit was not tested in this study. The activity of t Of the drug in patients with melanoma probably c KIT aberrations will be evaluated.106 Nilotinib Nilotinib is a second-generation tyrosine kinase inhibitor of c-KIT, PDGFR, and BCR-ABL. Nilotinib has anything similar Kr Forces against KIT and PDGFR, c compared to imatinib. 67 differ, however, the agents with respect to cellular Major transport, which is actively transported imatinib and nilotinib is transported passively.