1. A phase II study of tandutinib (MLN518), a selective inhibitor of type III tyrosine receptor kinases, in patients with metastatic renal cell carcinoma.
- Author
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Shepard DR, Cooney MM, Elson P, Bukowski RM, Dreicer R, Rini BI, and Garcia JA
- Subjects
- Aged, Antineoplastic Agents administration & dosage, Antineoplastic Agents adverse effects, Carcinoma, Renal Cell enzymology, Carcinoma, Renal Cell mortality, Carcinoma, Renal Cell secondary, Disease-Free Survival, Female, Humans, Kaplan-Meier Estimate, Kidney Neoplasms enzymology, Kidney Neoplasms mortality, Kidney Neoplasms pathology, Male, Middle Aged, Ohio, Piperazines administration & dosage, Piperazines adverse effects, Protein Kinase Inhibitors administration & dosage, Protein Kinase Inhibitors adverse effects, Quinazolines administration & dosage, Quinazolines adverse effects, Receptor Protein-Tyrosine Kinases metabolism, Time Factors, Treatment Outcome, Antineoplastic Agents therapeutic use, Carcinoma, Renal Cell drug therapy, Kidney Neoplasms drug therapy, Piperazines therapeutic use, Protein Kinase Inhibitors therapeutic use, Quinazolines therapeutic use, Receptor Protein-Tyrosine Kinases antagonists & inhibitors
- Abstract
Therapies which target VEGF and mTOR are now available for patients with metastatic renal cell carcinoma, but there is a continued need to develop agents for patients who become refractory to these initial agents. Tandutinib is a relatively selective inhibitor of type III tyrosine kinase receptor kinases with promising activity in some tumors. In this trial, 10 patients with metastatic renal cell carcinoma refractory to previous therapy with sunitinib or sorafenib (median age 61 years, 80% performance status 0, 60% intermediate MSKCC risk classification) received tandutinib 500 mg bid daily with RECIST-defined response as the primary endpoint and progression-free survival (PFS) and overall survival (OS) as secondary endpoints. No patient had more than 2 cycles of therapy and 50% of patients only received 1 cycle with 70% of patients discontinuing for progressive disease and 30% for toxicity. Tandutinib was not well tolerated with dose reduction in 60% of patients due to adverse events. The most common grade 3 toxicity was fatigue (30%). Tandutinib had no clinical activity and due to the excessive toxicity should not be developed further in patients with sunitinib or sorafenib-refractory metastatic renal cell carcinoma.
- Published
- 2012
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