Abstract | BACKGROUND: 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.
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Authors | BingHe Xu, YiLong Wu, Lin Shen, DingWei Ye, Annette Jappe, Azzeddine Cherfi, Hui Wang, RuiRong Yuan |
Journal | Journal of hematology & oncology
(J Hematol Oncol)
Vol. 4
Pg. 3
(Jan 13 2011)
ISSN: 1756-8722 [Electronic] England |
PMID | 21232120
(Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Everolimus
- Sirolimus
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Topics |
- Adult
- Aged
- Antineoplastic Agents
(administration & dosage, adverse effects, pharmacokinetics)
- Dose-Response Relationship, Drug
- Everolimus
- Female
- Humans
- Male
- Middle Aged
- Neoplasms
(drug therapy, metabolism)
- Sirolimus
(administration & dosage, adverse effects, analogs & derivatives, pharmacokinetics)
- Treatment Outcome
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