Two-dose-level confirmatory study of the pharmacokinetics and tolerability of everolimus in Chinese patients with advanced solid tumors

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• 作者：BingHe Xu (1)
  YiLong Wu (2)
  Lin Shen (3)
  DingWei Ye (4)
  Annette Jappe (5)
  Azzeddine Cherfi (5)
  Hui Wang (6)
  RuiRong Yuan (7) (8)
  
• 刊名：Journal of Hematology & Oncology
• 出版年：2011
• 出版时间：December 2011
• 年：2011
• 卷：4
• 期：1
• 全文大小：293KB
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• 作者单位：BingHe Xu (1)
  YiLong Wu (2)
  Lin Shen (3)
  DingWei Ye (4)
  Annette Jappe (5)
  Azzeddine Cherfi (5)
  Hui Wang (6)
  RuiRong Yuan (7) (8)
  
  1. Cancer Hospital Chinese Academy of Medical Sciences, Beijing, China
  2. Guandong General Hospital, Guandong, China
  3. Beijing Cancer Hospital, Beijing, China
  4. Cancer Hospital Fundan University, Shanghai, China
  5. Novartis Pharma AG, Basel, Switzerland
  6. Novartis Pharma Co., Ltd., Beijing, China
  7. Novartis Pharmaceuticals Corporation, Florham Park, NJ, USA
  8. New Jersey Medical School (UMDNJ), Newark, NJ, USA
  
• ISSN：1756-8722

文摘

Background This phase I, randomized, multicenter, open-label study investigated the pharmacokinetics, safety, and efficacy of the oral mammalian target of rapamycin inhibitor everolimus in Chinese patients with advanced solid tumors. Methods A total of 24 patients with advanced breast cancer (n = 6), gastric cancer (n = 6), non-small cell lung cancer (n = 6), or renal cell carcinoma (n = 6) who were refractory to/unsuitable for standard therapy were randomized 1:1 to oral everolimus 5 or 10 mg/day. Primary end points were pharmacokinetic parameters and safety and tolerability. Pharmacokinetic 24-h profiles were measured on day 15; trough level was measured on days 2, 8, 15, 16, and 22. Tolerability was assessed continuously. This final analysis was performed after all patients had received 6 months of study drug or had discontinued. Results Everolimus was absorbed rapidly; median Tmax was 3 h (range, 1-4) and 2 h (range, 0.9-6) in the 5 and 10 mg/day groups, respectively. Pharmacokinetic parameters increased dose proportionally from the 5 and 10 mg/day doses. Steady-state levels were achieved by day 8 or earlier. The most common adverse events suspected to be related to everolimus therapy were increased blood glucose (16.7% and 41.7%) and fatigue (16.7% and 33.3%) in the everolimus 5 and 10 mg/day dose cohorts, respectively. Best tumor response was stable disease in 10 (83%) and 6 (50%) patients in the 5 and 10 mg/day groups, respectively. Conclusions Everolimus 5 or 10 mg/day was well tolerated in Chinese patients with advanced solid tumors. The observed safety and pharmacokinetic profile of everolimus from this study were consistent with previous studies. Trial registration Chinese Health Authorities 2008L09346