Chemotherapy · 2016
A Phase I Trial of Temsirolimus and Pemetrexed in Patients with Advanced Non-Small Cell Lung Cancer.
Клиническое исследование I фазыСтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
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Waqar Saiama N, Baggstrom Maria Q, Morgensztern Daniel, Williams Kristina, Rigden Caron, Govindan Ramaswamy
Аннотация
BACKGROUND: Pemetrexed is an antifolate chemotherapeutic agent approved for use in non-small cell lung cancer (NSCLC). The mammalian target of rapamycin (mTOR) pathway is implicated in lung cancer development and inhibited by temsirolimus.
METHODS: We performed a phase I study evaluating the combination of pemetrexed and temsirolimus in advanced non-squamous NSCLC.
RESULTS: Eight patients were enrolled in this study. The dose-limiting toxicities included grade 4 thrombocytopenia, grade 3 leukopenia and grade 3 neutropenia. The maximum tolerated dose was determined to be pemetrexed 375 mg/m2 intravenously on day 1 and temsirolimus 25 mg intravenously on days 1, 8 and 15. No objective responses were noted and 3 patients had stable disease as the best response.
CONCLUSION: The combination of pemetrexed and temsirolimus is feasible and well tolerated. This combination may be further evaluated in patients with mTOR pathway activation, particularly in those with TSC1 or STK11 mutations.
METHODS: We performed a phase I study evaluating the combination of pemetrexed and temsirolimus in advanced non-squamous NSCLC.
RESULTS: Eight patients were enrolled in this study. The dose-limiting toxicities included grade 4 thrombocytopenia, grade 3 leukopenia and grade 3 neutropenia. The maximum tolerated dose was determined to be pemetrexed 375 mg/m2 intravenously on day 1 and temsirolimus 25 mg intravenously on days 1, 8 and 15. No objective responses were noted and 3 patients had stable disease as the best response.
CONCLUSION: The combination of pemetrexed and temsirolimus is feasible and well tolerated. This combination may be further evaluated in patients with mTOR pathway activation, particularly in those with TSC1 or STK11 mutations.
Предметные рубрики MeSH
AMP-Activated Protein Kinase KinasesAgedAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Non-Small-Cell LungFemaleHumansLung NeoplasmsMaleMaximum Tolerated DoseMiddle AgedMutationPemetrexedProtein Serine-Threonine KinasesSirolimusTOR Serine-Threonine KinasesTuberous Sclerosis Complex 1 ProteinTumor Suppressor Proteins