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10.1016/j.ejca.2015.06.115 http://scihub22266oqcxt.onion/10.1016/j.ejca.2015.06.115 C5693226!5693226 !26199039     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=26199039 &cmd=llinks): Failed to open stream: HTTP request failed! 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Results of a phase 1 trial combining ridaforolimus and MK-0752 in patients with advanced solid tumours |pdf=|usr=}}{{26199039 }} gab.com Text Results of a phase 1 trial combining ridaforolimus and MK-0752 in patients with advanced solid tumours JO: Eur J Cancer http://www.kidney.de/pget.php?&tw=1&pmid=26199039 #FOAvip BACKGROUND: The phosphatidylinositol 3-kinase/protein kinase-B/mammalian target of rapamycin (PI3K-AKT-mTOR) signalling pathway is aberrantly activated in several cancers. Notch signalling maintains cell proliferation, growth and metabolism in part by driving the PI3K pathway. Combining the mTOR inhibitor ridaforolimus with the Notch inhibitor MK-0752 may increase blockade of the PI3K pathway. METHODS: This phase I dose-escalation study (NCT01295632) aimed to define the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of combination oral ridaforolimus (rising doses starting at 20 mg, 5 days/week) and oral MK-0752 (1800 mg once weekly) in patients with solid tumours. No intrapatient dose escalation was permitted. RESULTS: Twenty eight patients were treated on study. Ridaforolimus doses were escalated from 20 to 30 mg/day. Among 14 evaluable patients receiving ridaforolimus 20 mg, one DLT (grade 2 stomatitis, second episode) was reported. Among eight evaluable patients receiving ridaforolimus 30 mg, three DLTs were reported (one each grade 3 stomatitis, grade 3 diarrhoea, and grade 3 asthenia). The MTD was 20 mg daily ridaforolimus 5 days/week+1800 mg weekly MK-0752. The most common drug-related adverse events included stomatitis, diarrhoea, decreased appetite, hyperglycaemia, thrombocytopenia, asthenia and rash. Two of 15 (13%) patients with head and neck squamous cell carcinoma (HNSCC) had responses: one with complete response and one with partial response. In addition, one patient experienced stable disease ?6 months. CONCLUSIONS: Combined ridaforolimus and MK-0752 showed activity in HNSCC. However, a high number of adverse events were reported at the MTD, which would require careful management during future clinical development. Twit Text FOAVip Results of a phase 1 trial combining ridaforolimus and MK-0752 in patients with advanced solid tumours ????Eur J Cancer http://www.kidney.de/pget.php?&tw=1&pmid=26199039 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=26199039 #FOAvip English Wikipedia <ref>{{Cite pmid|26199039 }}</ref> Results of a phase 1 trial combining ridaforolimus and MK-0752 in patients with advanced solid tumours #MMPMID26199039 Piha-Paul SA ; Munster PN ; Hollebecque A ; Argilés G ; Dajani O ; Cheng JD ; Wang R ; Swift A ; Tosolini A ; Gupta S Eur J Cancer 2015[Sep]; 51 (14 ): 1865-73 PMID26199039 show ga BACKGROUND: The phosphatidylinositol 3-kinase/protein kinase-B/mammalian target of rapamycin (PI3K-AKT-mTOR) signalling pathway is aberrantly activated in several cancers. Notch signalling maintains cell proliferation, growth and metabolism in part by driving the PI3K pathway. Combining the mTOR inhibitor ridaforolimus with the Notch inhibitor MK-0752 may increase blockade of the PI3K pathway. METHODS: This phase I dose-escalation study (NCT01295632) aimed to define the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of combination oral ridaforolimus (rising doses starting at 20 mg, 5 days/week) and oral MK-0752 (1800 mg once weekly) in patients with solid tumours. No intrapatient dose escalation was permitted. RESULTS: Twenty eight patients were treated on study. Ridaforolimus doses were escalated from 20 to 30 mg/day. Among 14 evaluable patients receiving ridaforolimus 20 mg, one DLT (grade 2 stomatitis, second episode) was reported. Among eight evaluable patients receiving ridaforolimus 30 mg, three DLTs were reported (one each grade 3 stomatitis, grade 3 diarrhoea, and grade 3 asthenia). The MTD was 20 mg daily ridaforolimus 5 days/week+1800 mg weekly MK-0752. The most common drug-related adverse events included stomatitis, diarrhoea, decreased appetite, hyperglycaemia, thrombocytopenia, asthenia and rash. Two of 15 (13%) patients with head and neck squamous cell carcinoma (HNSCC) had responses: one with complete response and one with partial response. In addition, one patient experienced stable disease ?6 months. CONCLUSIONS: Combined ridaforolimus and MK-0752 showed activity in HNSCC. However, a high number of adverse events were reported at the MTD, which would require careful management during future clinical development. |Administration, Oral [MESH] |Adult [MESH] |Aged [MESH] |Aged, 80 and over [MESH] |Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use [MESH] |Benzene Derivatives/administration & dosage [MESH] |Carcinoma, Squamous Cell/*drug therapy/enzymology/pathology [MESH] |Drug Administration Schedule [MESH] |Europe [MESH] |Female [MESH] |Head and Neck Neoplasms/*drug therapy/enzymology/pathology [MESH] |Humans [MESH] |Male [MESH] |Maximum Tolerated Dose [MESH] |Middle Aged [MESH] |Molecular Targeted Therapy [MESH] |Multimodal Imaging/methods [MESH] |Positron-Emission Tomography [MESH] |Propionates/administration & dosage [MESH] |Protein Kinase Inhibitors/administration & dosage [MESH] |Signal Transduction/drug effects [MESH] |Sirolimus/administration & dosage/analogs & derivatives [MESH] |Squamous Cell Carcinoma of Head and Neck [MESH] |Sulfones/administration & dosage [MESH] |Time Factors [MESH] |Tomography, X-Ray Computed [MESH] |Treatment Outcome [MESH]Results of a phase 1 trial combining ridaforolimus and MK-0752 in pati(epmc).pdf DeepDyve Pubget Overpricing