A phase-1b study of everolimus plus paclitaxel in patients with small-cell lung cancer

作者：Sun J M; Kim J R; Do I G; Lee S Y; Lee J; Choi Y L; Ahn J S; Ahn M J; Park K^*

来源：British Journal of Cancer, 2013, 109(6): 1482-1487.

DOI：10.1038/bjc.2013.467

• everolimus
• paclitaxel
• phase-1b
• small-cell lung cancer

Background: The mammalian target of rapamycin (mTOR) pathway is dysregulated in small-cell lung cancer (SCLC) and everolimus is an oral mTOR inhibitor. %26lt;br%26gt;Methods: This phase-1b study assessed everolimus safety at the levels of 2.5, 5, or 10mg once daily in combination with paclitaxel (175mg m(-2)) once every 3 weeks in previously treated SCLC patients. The primary end point was to determine the maximum tolerated dose of everolimus. %26lt;br%26gt;Results: Among 21 enrolled patients, common drug-related adverse events were anaemia, neutropenia, thrombocytopenia, pain, hyperglycemia, and stomatitis. Out of 11 evaluable patients treated with everolimus at the level of 5 mg, 1 patient experienced dose-limiting toxicity (DLT) of grade 4 febrile neutropenia and grade 3 thrombocytopenia. The other two DLTs (grade 4 thrombocytopenia and grade 3 hyperglycemia) occurred in two out of three patients receiving everolimus 10 mg. The overall objective response rate was 28%. %26lt;br%26gt;Conclusion: Everolimus showed an acceptable safety profile and preliminary antitumour activity at the dose of 5mg once daily when combined with 3-weekly paclitaxel 175mg m(-2) in patients with SCLC.

• 出版日期2013-9-17