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Agent shows superior safety as first-line RCC therapy


Atlanta-Sorafenib tosylate (Nexavar), a newer oral multi-kinase inhibitor that targets tumor growth and vascularization, was generally well tolerated by patients with metastatic clear-cell renal cell carcinoma in a randomized phase II trial that compared the efficacy and tolerability of the drug with that of interferon in first-line therapy. Study results were presented by Bernard Escudier, MD, head of the immunotherapy and innovative therapy unit at Institut Gustave Roussy Villejuif, Cedex, France, at the American Society of Clinical Oncology annual meeting here.

According to Dr. Escudier, the trial confirmed previous research findings showing that interferon, which is widely used in the treatment of metastatic RCC, has modest activity, with response rates of 7.5% to 15%, median progression-free survival of about 20 weeks, and response duration of 4 to 6 months, whereas sorafenib has greater clinical efficacy as a second-line treatment after interferon/interleukin-2 (IFN/IL-2) therapy has failed.

Of 189 patients enrolled, 97 received continuous oral sorafenib, 400 mg twice daily, and 92 received interferon, 9 million units three times weekly. Patients receiving the drug had the option of dose escalation to sorafenib, 600 mg twice daily; those in the placebo group had the option of crossing over to sorafenib if their disease progressed.

Median age was 62 years; 82% had prior nephrectomy. Fifty-seven percent of patients had low Memorial Sloan-Kettering Cancer Center scores; 41% had intermediate scores, and 1% had high scores. In the sorafenib group, 55.3% versus 44.7% of the placebo group had Eastern Cooperative Oncology Group performance status scores of 0 or 1.

Gauging adverse events

As of January 2006, progression-free survival events have been reported for 64 patients (34%). Preliminary data showed drug-related adverse effects of any severity in 50.5% of the sorafenib group compared with 51.6% of patients receiving interferon. Of those experiencing grade 3 or higher events, 8.2% were in the sorafenib group and 11% were in the interferon group. One patient in the sorafenib group and five patients in the interferon group withdrew from the study due to adverse events.

The most common adverse events in patients treated with sorafenib versus interferon were diarrhea (24.7% vs. 5.5%, respectively), fatigue (14.4% vs. 20.9%), fever (2.1% vs. 18.7%), hypertension (13.4% vs. 0%), nausea (5.2% vs. 13.2%), flu-like syndrome (1.0% vs. 6.6%), hand/foot skin reaction (6.2% vs. 0%), and rash/desquamation (4.1% vs. 0%). Five patients who received interferon withdrew from treatment due to adverse events, whereas only one patient stopped taking sorafenib for that reason.

Drug-related grade 3 metabolic or laboratory-related abnormalities for the sorafenib and interferon groups included hypophosphatemia (21.7% vs. 0%, respectively), lipase elevation (5.6% vs. 11.1%), anemia (0% vs. 5.3%), and hypoalbuminemia (0% vs. 3.6%). No grade 4 abnormalities were reported.

Although the study was also designed to compare the relative efficacy of interferon and sorafenib as first-line therapies, the data were considered premature for efficacy analysis, Dr. Escudier said.

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