In this trial design, all enrolled patients were given a 12 week "run in" course of sorafenib and were then evaluated for evidence of response. Those patients that demonstrated a response to therapy (>25% tumor shrinkage) were continued on therapy. Those patients that demonstrated greater than 25% tumor growth were taken off therapy, considered treatment failures, and moved on to other systemic therapy options. Those patients with stable disease or less than 25% tumor shrinkage were randomized to either continuing sorafenib or placebo, the idea being that if their disease stability was due to sorafenib, disease progression would be seen in the placebo group. This trial design allows for a placebo control while minimizing the exposure of patients to the placebo. Here, the results of this trial are reported by Ratain and colleagues.

There were 202 patients who received therapy in the 12 week run-in period, 179 of whom had had a prior nephrectomy. Of these, 187 patients (93%) completed therapy for the 12 weeks. Seventy-three patients (36%) had tumor shrinkage >25% and were continued on therapy. Fifty-one patients (25%) demonstrated tumor growth and were taken off study. Sixty-nine patients (36%) had tumor measurements that remained within 25% of baseline levels and were therefore eligible to be randomized to receive continued sorafenib versus placebo. Of these, 65 patients were randomized. After 24 weeks, 50% of patients receiving sorafenib remained progression free, versus 18% receiving placebo (p=0.0077). The progression free survival from randomization was 24 weeks for the sorafenib arm and 6 weeks for the placebo arm (p=0.0087). The main toxicity seen in the trial was fatigue (73%) and rash (66%). The most common grade 3 or 4 toxicity was hypertension (31%). Sorafenib (and sunitinib) are now approved for metastatic renal cell carcinoma therapy in the US. While not without toxicity, most believe these agents represent a significant advance in treatment that will prolong the lives of patients significantly.

J Clin Oncol 24(16): Epub April 24, 2006

Renal Cancer Section

Written by Christopher G. Wood, MD, a Contributing Editor with UroToday.

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