Dual regimen works better than either medication alone in patients with advanced RCC.


Using sorafenib in combination with interferon alfa-2b elicits a greater treatment response in patients with advanced renal cancer than either agent alone, according to two studies. Researchers caution, however, that any benefit of the dual regimen must be weighed against a potential increase in toxicities.

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In one study, Christopher W. Ryan, MD, of the Oregon Health and Science University in Portland, and his colleagues evaluated the combination therapy as first-line treatment in patients with metastatic or unresectable renal cell carcinoma (RCC).


“The confirmed response rate for the combination of sorafenib and interferon in advanced renal cell carcinoma is greater than expected with either interferon or sorafenib alone,” the authors concluded.


In the other study, a team led by Jared A. Gollob, MD, of DukeUniversityMedicalCenter in Durham, N.C., tested the dual regimen as first- or second-line treatment in patients with metastatic renal cell carcinoma. The group concluded that the combination “has substantial activity” in treatment-naïve and interleukin-2 (IL-2) treated patients.


The findings of both phase II studies were published in the Journal of Clinical Oncology (2007;25:3288-3295;3296-3301).


The study by Dr. Ryan and his colleagues focused on 62 patients who were treated with sorafenib 400 mg orally twice daily and interferon alfa-2b 10 million U three times weekly. Each four-week treatment period was considered one cycle. Response assessment was based on the Response Evaluation Criteria in Solid Tumors (RECIST).


Of the 62 patients, 12 (19%) had an objective confirmed response, and another 31 (50%) had an unconfirmed partial response or stable disease as best response, the researchers reported. The most common adverse effects were fatigue, anorexia, anemia, diarrhea, nausea, fever, rigors/

chills, leukopenia, and transaminase elevation.  


Confirmed RECIST response rates in patients with advanced RCC have not exceeded 10% in all studies of sorafenib monotherapy and most studies of interferon monotherapy. The authors said that their results “suggest that combination treatment with these two agents induces a higher incidence of protocol-defined responses than with either single agent alone.”


The study also showed that median progression-free survival was seven months. Previous studies of advanced RCC patients have shown that sorafenib alone used as second-line treatment and interferon alone used as first-line treatment are associated with median progression-free survival of 5.5 and 5.0 months, respectively.


Although the seven-month median progression-free survival observed in the new study compares favorably, the investigators noted, “this finding must not be overinterpreted given the small sample size and nonrandomized nature of this study.”


“In the development of new combinations for renal carcinoma, any incremental clinical benefit achieved with combination therapy must be balanced with the potential increase in toxicity,” the authors wrote. “It is not obvious that the increased response rate we observed with sorafenib plus interferon treatment justifies the relatively high toxicity profile of this regimen.”


The study by Dr. Gollob’s group enrolled 40 patients. These patients received eight-week cycles of sorafenib 400 mg orally twice daily and interferon alfa-2b 10 million U three times a week followed by a two-week break.


Eleven patients (28%) had a partial response to treatment and two (5%) had a complete response. Re-sponses were seen in treatment-naïve and IL-2 treated patients within the first two cycles. The response rate is encouraging, the authors noted, and suggest a favorable interaction between interferon alfa-2b and sorafenib because the expected response rate to either drug alone is about 5% to 10%.


The median duration of response was 12 months, according to researchers. With a median follow-up of 14 months, median progression-free survival was 10 months, which the investigators said compares favorably with the 5.5-month medical progression-free survival observed with sorafenib alone in cytokine-refractory patients.


The most common toxicities among the patients were fatigue, anorexia, anemia, diarrhea, rash, nausea, weight loss, and hypophosphatemia. “The toxicity exceeded that of either drug alone, but dose reductions and breaks between cycles allowed for chronic therapy,” the authors concluded. Dose reductions were required in 65% of subjects treated.