BAYER/ONYXOral therapy approved for the treatment of advanced renal cell carcinoma
This multikinase inhibitor targets several serine/threonine and receptor tyrosine kinases, thereby reducing tumor angiogenesis and proliferation. Sorafenib was approved on December 20, 2005, for the treatment of advanced renal cell carcinoma.
Efficacy. The efficacy of sorafenib for the treatment of renal cell carcinoma was evaluated in 2 randomized, controlled clinical trials. Study 1 randomized 769 patients with advanced renal cell carcinoma to either sorafenib 400 mg twice daily or placebo. The primary end points in the study were overall survival and progression-free survival (PFS). The median PFS for patients randomized to sorafenib was 167 days compared to 84 days for patients randomized to placebo. The estimated hazard ratio for the risk of progression with sorafenib compared with placebo was 0.44 (95% CI, 0.35–0.55). Study 2 was a randomized discontinuation trial in 222 patients with metastatic malignancies, including renal cell carcinoma. The primary end point was the percentage of patients remaining progression-free at 24 weeks. The progression-free rate was significantly higher in patients randomized to sorafenib (50%) than in patients randomized to placebo (18%) (P=.0077). Progression-free survival was also significantly longer in the sorafenib group (163 d) than in the placebo group (41 d) (P=.0001, HR=0.29).
Dosing. The recommended daily dose of sorafenib is 400 mg taken twice daily, without food (at least 1 h before or 2 h after eating). Treatment should continue until the patient is no longer clinically benefiting from therapy or until unacceptable toxicity occurs. Management of suspected adverse drug reactions may require temporary interruption and/or dose reduction of sorafenib therapy. When necessary, the sorafenib dose may be reduced to 400 mg once daily. If additional reduction is required, sorafenib therapy may be reduced to a single 400-mg dose every other day.