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- Ahmad Tarhini
- Authors' Affiliations: 1University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania and 2Penn State Hershey Cancer Institute, Hershey, Pennsylvania
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- Athanasios Kotsakis
- Authors' Affiliations: 1University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania and 2Penn State Hershey Cancer Institute, Hershey, Pennsylvania
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- William Gooding
- Authors' Affiliations: 1University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania and 2Penn State Hershey Cancer Institute, Hershey, Pennsylvania
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- Yongli Shuai
- Authors' Affiliations: 1University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania and 2Penn State Hershey Cancer Institute, Hershey, Pennsylvania
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- Daniel Petro
- Authors' Affiliations: 1University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania and 2Penn State Hershey Cancer Institute, Hershey, Pennsylvania
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- David Friedland
- Authors' Affiliations: 1University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania and 2Penn State Hershey Cancer Institute, Hershey, Pennsylvania
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- Chandra P. Belani
- Authors' Affiliations: 1University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania and 2Penn State Hershey Cancer Institute, Hershey, Pennsylvania
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- Sanja Dacic
- Authors' Affiliations: 1University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania and 2Penn State Hershey Cancer Institute, Hershey, Pennsylvania
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- Athanassios Argiris
- Authors' Affiliations: 1University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania and 2Penn State Hershey Cancer Institute, Hershey, Pennsylvania
抄録
<jats:title>Abstract</jats:title> <jats:p>Purpose: Mammalian target of rapamycin (mTOR) is a promising target in small cell lung cancer (SCLC). We designed a phase II study of everolimus, an mTOR inhibitor, in previously treated, relapsed SCLC.</jats:p> <jats:p>Experimental Design: Patients were treated with everolimus 10 mg orally daily until disease progression. The primary endpoint was disease control rate (DCR) at 6 weeks. PI3K/Akt signaling pathway biomarkers were evaluated on baseline tumor tissue.</jats:p> <jats:p>Results: A total of 40 patients were treated: 23 had 1 prior regimen/sensitive relapse, 4 had 1 prior regimen/refractory, and 13 had 2 prior regimens. Twenty-eight patients received 2 or more cycles of everolimus, 7 received 1 cycle, and 5 did not complete the first cycle. Best response in 35 evaluable patients: 1 (3%) partial response (in sensitive relapse), 8 (23%) stable disease, and 26 (74%) progression; DCR at 6 weeks was 26% (95% CI = 11–40). Median survival was 6.7 months and median time to progression was 1.3 months. Grade 3 toxicities included thrombocytopenia (n = 2), neutropenia (n = 2), infection (n = 2), pneumonitis (n = 1), fatigue (n = 1), elevated transaminases (n = 1), diarrhea (n = 2), and acute renal failure (n = 1). High phosphorylated AKT expression was modestly associated with overall survival (HR = 2.07; 95% CI = 0.97–4.43). Baseline S6 kinase protein expression was significantly higher in patients with disease control versus patients with progression (P = 0.0093).</jats:p> <jats:p>Conclusions: Everolimus was well tolerated but had limited single-agent antitumor activity in unselected previously treated patients with relapsed SCLC. Further evaluation in combination regimens for patients with sensitive relapse may be considered. Clin Cancer Res; 16(23); 5900–7. ©2010 AACR.</jats:p>
収録刊行物
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- Clinical Cancer Research
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Clinical Cancer Research 16 (23), 5900-5907, 2010-12-01
American Association for Cancer Research (AACR)