title: A phase-1b study of everolimus plus paclitaxel in patients with small-cell lung cancer.
abstract: BACKGROUND
  The mammalian target of rapamycin (mTOR) pathway is dysregulated in small-cell lung cancer (SCLC) and everolimus is an oral mTOR inhibitor.
  
  
  METHODS
  This phase-1b study assessed everolimus safety at the levels of 2.5, 5, or 10 mg once daily in combination with paclitaxel (175 mg m(-2)) once every 3 weeks in previously treated SCLC patients. The primary end point was to determine the maximum tolerated dose of everolimus.
  
  
  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%.
  
  
  CONCLUSIONS
  Everolimus showed an acceptable safety profile and preliminary antitumour activity at the dose of 5 mg once daily when combined with 3-weekly paclitaxel 175 mg m(-2) in patients with SCLC.
authors: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Korea.
authors: J M
authors: JM
authors: Sun
authors: J R
authors: JR
authors: Kim
authors: I G
authors: IG
authors: Do
authors: S Y
authors: SY
authors: Lee
authors: J
authors: J
authors: Lee
authors: Y L
authors: YL
authors: Choi
authors: J S
authors: JS
authors: Ahn
authors: M J
authors: MJ
authors: Ahn
authors: K
authors: K
authors: Park
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D000068338:Everolimus; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy*
chemical_list: D000068338:Everolimus; D017239:Paclitaxel; D020123:Sirolimus
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