Sunitinib is a highly selective molecule that inhibits multiple receptor tyrosine kinases, some of which are implicated in tumour growth, pathologic angiogenesis and metastatic progression of cancer.
In an open-label study of 97 patients with GIST, sunitinib was given in a four weeks on, two weeks off schedule until the disease progressed or patients were withdrawn for other reasons. At the end of the study the median time to disease progression was 34 weeks.
In a subsequent phase III placebo-controlled study involving 312 GIST patients with imatinib resistance or intolerance, sunitinib significantly prolonged the time to disease progression. In this study the median time to progression was 28.9 weeks compared with 5.1 weeks in the placebo group. At disease progression, treatment was unblinded and patients in the placebo group were offered crossover to sunitinib, while those in the treatment group were allowed to continue. The difference in overall survival was statistically in favour of sunitinib, with the risk of death double in the placebo group. The percentages of deaths were 14% for sunitinib as opposed to 25% for placebo. However, at the time of analysis the data were not mature enough to determine overall survival benefit.
In a phase II study of 63 patients with MRCC, sunitinib was given on a four weeks on, two weeks off schedule. The primary efficacy endpoint was taken as the objective response rate based on RECIST. In this study the objective response rate was 36.5% and the median time to progression was 37.7 weeks. In a similar open-label multicentre study of 106 patients, the objective response rate was 38% but the duration of response and overall survival had not been reached by the time of analysis.
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