is cF treatment crizotinib 38 days. Crizotinib is currently under active clinical investigation in NSCLC. In addition, Phase I-II study in patients with advanced b Sartigen tumors such as neuroblastoma or ALCL was conducted. Second generation ALK inhibitors as PA 26 113 X 276 and are considered to be potent and selective inhibitors of ALK than crizotinib. AP 26113, an orally bioavailable ALK with an Roscovitine unknown structure is developed by Ariad. W During the pr-Clinical study was 26 113 AP shown to inhibit not only wild type ALK, but mutated forms of ALK, which are resistant to the first generation ALK inhibitor like crizotinib. Other studies have shown, AP 26113 betr Gt at least 10 times more potent and selective inhibition of ALK crizotinib. The clinical development of inhibitors of ALK in 2009, the j HAZARDOUS meeting of ASCO, Kwat et al. reported on the results of the Phase I dose escalation and extended phase II study crizotinib. Thirty-seven patients with advanced solid tumors, including three patients with NSCLC were included in Phase I.
The maximum tolerated dose of crizotinib was 250 mg twice t Resembled orally and 2 DLT fatigue were in the h t Heren dose of 300 mg twice resembled observed. The main side effects include fatigue, nausea, vomiting and diarrhea, but they were manageable and reversible. There was a partial response in a patient with sarcoma ALK rearrangement. In addition, a dramatic clinical response in patients with NSCLC harboring EML4 ALK rearrangement observed. Therefore, a phase II study was t GSK1120212 with extended crizotinib 250 mg twice Resembled in NSCLC patients harboring EML4-ALK performed 27 tumor detected by FISH. In the first 19 evaluable patients, there were 17 patients with adenocarcinoma and 14 non-smokers. The overall response rate was 53, and the speed was embroidered with the disease 79 to 8 weeks. Only 4 patients one progression after 8 weeks of treatment, although more than 60 patients have U 2 or more lines of treatment prior to entry into the study again.
Bang et al. pr presents the results of the monitoring phase II study expanded crizotinib in patients with NSCLC EML4 ALK rearrangement in 2010 ASCO Annual Meeting. Eighty-two patients were evaluable, 96 had adenocarcinoma, and 95 had never smoked 76 before treatment. Overall RR was 57, with a gesch Tzten survival rate free 6 months of 72 and 87 DCR at least 8 weeks. The median progression free survival was not free yet mature, and the median duration of treatment was 25.5 weeks. Radiological responses were usually w During the first or second restaging scanner observed. The main side effects are nausea, diarrhea, and changes Sehst Accommodation on the dark without a light anomaly in the eye examination. The results of this phase II study were recently published Ffentlicht. Based on these encouraging results, a randomized phase III trial comparing crizotinib began with standard second-line cytotoxic chemotherapy of docetaxel and pemetrexed in patients with ALK positive NSCLC. The COMBINATIO