In a phase II study involving 111 patients with refractory metastatic RCC, partial response was seen in 7% and clinical benefit rate (i.e., patients who either exhibited a complete response, a partial response, or had stable disease) for at least 24 weeks was 51%, with median time to progression of 5.8 months (Atkins et al, 2004).
In RCC trials response criteria were in accordance to RECIST or WHO criteria; however, these were explicitly mentioned only in 5 trials [16], [55], [56], [58], [61].
In the highly vascular metastatic tumors hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC), successful response to anti-angiogenic therapy has been associated with the use of sunitinib (Sutent®) and sorafenib (Nexavar®), respectively.
In a randomized phase III trial comparing sorafenib with placebo as second-line therapy for RCC, the response rate to sorafenib was 10%, and the stable disease rate was 74%, with the median progression-free survival time being 5.5 months in the sorafenib group versus 2.8 months in the placebo group [ 29].
We propose that caveolin-1 may serve as a 'gatekeeper' for activation of the hypoxia-inducible factor (HIF) pathway a downstream effector molecule of mTOR that accumulates in RCC in response to the loss of function of VHL and promotes angiogenesis, vascular invasion and chemoresistance (Patel et al, 2006).
Among patients with sarcomatoid RCC, partial responses with VEGF inhibitors were limited to patients who had underlying CC histology and <20% sarcomatoid elements (Golshayan et al, 2009).
Epidermal growth factor receptor (EGFR) and tumour growth factor alpha (TGF α) are frequently overexpressed in renal cell carcinoma (RCC) yet responses to single-agent EGFR inhibitors are uncommon.
Among 34 patients with RCC, objective responses occurred in four of 17 patients (24%) treated with a dose of 1 mg/kg and in five of 16 patients (31%) treated with 10 mg/kg.
