EVEROLIMUS IN THE TREATMENT FOR METASTATIC RENAL CANCER
https://doi.org/10.17650/1726-9776-2010-6-3-19-24
Abstract
Target drugs acting via the HIF/VEGF pathway show a steady-state clinical effect in treating patients with metastatic renal cell carcinoma (RCC). However, to continue therapy in patients with developing resistance in the prolonged use of tyrosine kinase inhibitors remained unsolved, which brought about a search for alternative pathogenetic pathways and new effective appropriate medicines. One of its solutions was the mTOR pathway and everolimus acting via it. Motzer et al. conducted the RECORD-1 phase III international multicenter randomized double-blind placebo-controlled study of the efficiency of everolimus. The study enrolled 410 patients with metastatic RCC that progressed during target therapy with sunitinib and/or sorafenib. The study was interrupted before the appointed time, as recommended by the Independent Data Monitoring Committee since the established effectiveness threshold values and conformity criteria for a positive study result were achieved. According to an independent centralized assessment, everolimus reduced the risk for disease progression by 70% (p < 0.0001). The median progression-free survival was longer in the everolimus group than that in the placebo group, which was 4.9 and 1.9 months, respectively (p < 0.0001). Final double-blind analysis showed a partial response in 5 (2%) patients and disease stabilization in 185 (67%) patients in the everolimus group; there were no patients by the former indicator and 45 (32%) patients by the latter in the placebo group. The final findings showed no statistically significant difference in overall survival rates between the groups: the median overall survival was 14.78 and 14.39 months in the everolimus and placebo groups, respectively (p = 0.177). This might be due to a cross impact because 79 (81%) of the 98 patients from the placebo group were switched over to open-labeled everolimus taking after disease progression. Everolimus demonstrated a good tolerability and safety. Grade III-IV toxicity was recorded in 5% of patients. In the everolimus-taking patients, the most common adverse reactions of all severity degrees were stomatitis (36%), eruption (28%), fatigue (23%), asthenia (22%), and diarrhea (21%). The hematological reactions included anemia (25%), hypercholesterolemia (18%), and hyperglycemia (8%). Everolimus is now the first and only registered drug to treat metastatic RCC if therapy with tyrosine kinase inhibitors is ineffective.
About the Authors
B. Ya. Alekseyev
P.A. Herzen Moscow Research Oncological Institute
Russian Federation
Russian Federation
A. S. Kalpinsky
P.A. Herzen Moscow Research Oncological Institute
Russian Federation
Russian Federation
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Review
For citations:
Alekseyev B.Ya., Kalpinsky A.S. EVEROLIMUS IN THE TREATMENT FOR METASTATIC RENAL CANCER. Cancer Urology. 2010;6(3):19-24. (In Russ.) https://doi.org/10.17650/1726-9776-2010-6-3-19-24
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