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Atkins MB , Hidalgo M , Stadler WM , Logan TF , Dutcher JP , Hudes GR , Park Y , Lion SH , Marshall B , Boni JP , Dukart G , Sherman ML
Randomized phase II study of multiple dose levels of CCI-779, a novel mammalian target of rapamycin kinase inhibitor, in patients with advanced refractory renal cell carcinoma
Journal of Clinical Oncology. 2004 Mar;22(5) :909-918
AbstractPurpose To evaluate the efficacy, safety, and pharmacokinetics of multiple doses of CCI-779, a novel mammalian target of rapamycin kinase inhibitor, in patients with advanced refractory renal cell carcinoma (RCC). Patients and Methods Patients (n = 111) were randomly assigned to receive 25, 75, or 250 mg CCI-779 weekly as a 30-minute intravenous infusion. Patients were evaluated for tumor response, time to tumor progression, survival, and adverse events. Blood samples were collected to determine CCI-779 pharmacokinetics. Results CCI-779 produced an objective response rate of 7% (one complete response and seven partial responses) and minor responses in 26% of these advanced RCC patients. Median time to tumor progression was 5.8 months and median survival was 15.0 months. The most frequently occurring CCI-779-related adverse events of all grades were maculopapular rash (76%), mucositis (70%), asthenia (50%), and nausea (43%). The most frequently occurring grade 3 or 4 adverse events were hyperglycemia (17%), hypophosphatemia (13%), anemia (9%), and hypertriglyceridemia (6%). Neither toxicity nor efficacy was significantly influenced by CCI-779 dose level. Patients were retrospectively classified into good-, intermediate-, or poor-risk groups on the basis of criteria used by Motzer et al for a first-line metastatic RCC population treated with interferon alfa. Within each risk group, the median survivals of patients at each dose level were similar. Conclusion In patients with advanced RCC, CCI-779 showed antitumor activity and encouraging survival and was generally well tolerated over the three dose levels tested. (C) 2004 by American Society of Clinical Oncology.
NotesEnglish Article Clinical Medicine (CM); Life Sciences (LS) Atkins, MB; Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol Oncol, E Campus,Kirstein 158, Boston, MA 02215 USA. 0732-183X