A Cochrane review [Abstract] 1 included 19 studies with a total of 5 316 subjects. Six RCTs evaluated five agents in first line therapy for advanced renal cancer.
Temsirolimus was compared to interferon-alpha in a poor-risk patient group (one study, n=626). Patients who received temsirolimus had longer overall survival (OS, HR 0.73; 95% CI 0.58 to 0.92) and progression-free survival (P<0.001) than patients who received interferon. Temsirolimus had diverse toxicities but severe adverse reactions more common in the interferon arm.
Bevacizumab in combination with interferon-alpha was compared to interferon alone (one study, n=649). Median duration of progression-free survival (PFS) was significantly longer in the bevacizumab plus interferon-alpha group than in the control group (HR 0.61; 95% CI 0.51 to 0.73). Toxicity was greater for patients on the combination arm and 28% of patients had to discontinue a component of combination therapy versus 12% for interferon plus placebo.
Sunitinib was compared to interferon-alpha (one study, n=750). Median PFS was significantly longer in sunitinib group (HR 0.54; 95% CI 0.44 to 0.66). Severe treatment-related fatigue was more frequent in patients on interferon, whereas other toxicities were more frequent for sunitinib.
Sorafenib was compared to first-line interferon-alpha. At the standard dose of sorafenib there was no significant difference in PFS.
There was no significant difference in disease-related endpoints when thalidomide was added to interferon but the detrimental effect of therapy on global quality-of-life (2 studies, n=362).
Another phase III study 2 compared bevacizumab plus interferon-alpha to interferon alone. PFS was significantly longer for the combination group (HR 0.71; 95% CI 0.61 to 0.83) but difference in OS did not reach statistical significance (HR 0.86; 95% CI 0.73 to 1.01).
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