INTRODUCTION: The epidermal growth factor receptor inhibitor erlotinib is an approved treatment for chemotherapy-refractory advanced non-small-cell lung cancer (NSCLC). Because activated epidermal growth factor receptor signals through the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (mTOR) pathway, adding the oral mTOR inhibitor everolimus to erlotinib may improve efficacy by blocking multiple components of the same pathway. We conducted a phase I study to determine feasible dosages of combination therapy with erlotinib and everolimus for previously treated metastatic or unresectable NSCLC. METHODS:Participants had advanced NSCLC progressing after two or less previous chemotherapy regimens. Feasibility of daily/weekly everolimus plus daily erlotinib was determined using a 6 + 6 dose-escalation design based on the rate of dose-limiting toxicities. Antitumor activity was assessed by the Response Evaluation Criteria In Solid Tumors study. RESULTS: Of the 94 patients enrolled, 90% had stage IV NSCLC, 19% never smoked, and 15% were current smokers. Eighty-nine patients experienced one or more adverse events possibly related to any study medication. The most common dose-limiting toxicities were stomatitis (n = 5), rash (n = 4), and diarrhea (n = 3). Maximum tolerated doses were everolimus 5 mg per day or 50 mg per week plus erlotinib 150 mg per day. In daily everolimus cohorts (n = 74), nine patients achieved a complete/partial response and 28 had stable disease (median duration disease control, 9.3 months). In weekly everolimus cohorts (n = 20), no tumor response was observed; seven patients had stable disease (median duration, 9.6 months). CONCLUSIONS: Combination therapy with everolimus 5 mg per day or 50 mg per week and erlotinib 150 mg per day provided acceptable tolerability and disease control. A randomized phase II study evaluating this combination in comparison with erlotinib alone is complete and is being analyzed.
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INTRODUCTION: The epidermal growth factor receptor inhibitor erlotinib is an approved treatment for chemotherapy-refractory advanced non-small-cell lung cancer (NSCLC). Because activated epidermal growth factor receptor signals through the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (mTOR) pathway, adding the oral mTOR inhibitor everolimus to erlotinib may improve efficacy by blocking multiple components of the same pathway. We conducted a phase I study to determine feasible dosages of combination therapy with erlotinib and everolimus for previously treated metastatic or unresectable NSCLC. METHODS:Participants had advanced NSCLC progressing after two or less previous chemotherapy regimens. Feasibility of daily/weekly everolimus plus daily erlotinib was determined using a 6 + 6 dose-escalation design based on the rate of dose-limiting toxicities. Antitumor activity was assessed by the Response Evaluation Criteria In Solid Tumors study. RESULTS: Of the 94 patients enrolled, 90% had stage IV NSCLC, 19% never smoked, and 15% were current smokers. Eighty-nine patients experienced one or more adverse events possibly related to any study medication. The most common dose-limiting toxicities were stomatitis (n = 5), rash (n = 4), and diarrhea (n = 3). Maximum tolerated doses were everolimus 5 mg per day or 50 mg per week plus erlotinib 150 mg per day. In daily everolimus cohorts (n = 74), nine patients achieved a complete/partial response and 28 had stable disease (median duration disease control, 9.3 months). In weekly everolimus cohorts (n = 20), no tumor response was observed; seven patients had stable disease (median duration, 9.6 months). CONCLUSIONS: Combination therapy with everolimus 5 mg per day or 50 mg per week and erlotinib 150 mg per day provided acceptable tolerability and disease control. A randomized phase II study evaluating this combination in comparison with erlotinib alone is complete and is being analyzed.
Authors: Ramon Andrade De Mello; Pedro Nazareth Aguiar; Hakaru Tadokoro; Tállita Meciany Farias-Vieira; Pedro Castelo-Branco; Gilberto de Lima Lopes; Daniel Humberto Pozza Journal: J Thorac Dis Date: 2018-06 Impact factor: 2.895
Authors: E Massarelli; H Lin; L E Ginsberg; H T Tran; J J Lee; J R Canales; M D Williams; G R Blumenschein; C Lu; J V Heymach; M S Kies; V Papadimitrakopoulou Journal: Ann Oncol Date: 2015-05-29 Impact factor: 32.976
Authors: Shun-Qing Liang; Elias D Bührer; Sabina Berezowska; Thomas M Marti; Duo Xu; Laurène Froment; Haitang Yang; Sean R R Hall; Erik Vassella; Zhang Yang; Gregor J Kocher; Michael A Amrein; Carsten Riether; Adrian F Ochsenbein; Ralph A Schmid; Ren-Wang Peng Journal: Oncogene Date: 2018-08-31 Impact factor: 9.867
Authors: Taofeek K Owonikoko; Suresh S Ramalingam; Daniel L Miller; Seth D Force; Gabriel L Sica; Jennifer Mendel; Zhengjia Chen; Andre Rogatko; Mourad Tighiouart; R Donald Harvey; Sungjin Kim; Nabil F Saba; Allan Pickens; Madhusmita Behera; Robert W Fu; Michael R Rossi; William F Auffermann; William E Torres; Rabih Bechara; Xingming Deng; Shi-Yong Sun; Haian Fu; Anthony A Gal; Fadlo R Khuri Journal: Clin Cancer Res Date: 2015-02-11 Impact factor: 12.531