Trying to improve on the activity of Interferon-Alpha in metastatic renal cell carcinoma

Interferon-alpha (IFN) has been a mainstay in the systemic treatment of metastatic renal cell carcinoma (RCC) for decades, with response rates ranging from 3-15%.

Unlike interleukin 2, it has shown a survival benefit for patients in phase III randomized trials. Recent advances in the development of targeted therapy for metastatic RCC may sideline IFN as a first choice in therapy naïve patients, but research continues with therapies in combination with IFN to improve on historical results. Here, Kinouchi and colleagues, out of Japan, report on a phase III randomized trial comparing IFN alone to IFN with the type 2 histamine receptor antagonist cimetidine, a combination that had previously proved beneficial for patients with metastatic RCC in phase II trials.

Over a 4 year period, 71 patients from 32 institutions were accrued to this phase III trial with endpoints of response and time to progression. In the IFN arm, there was 1 complete response (CR) and 4 partial responses (PR), with 16 patients demonstrating stable disease, for a response rate of 13.9%. In the IFN + cimetidine arm, there were 2 CR, 8 PR, and 13 patients with stable disease, for a response rate of 28.6%. These response rates were not statistically significantly different (p=0.13). In the IFN arm, the median time to progression was 112 days, which was not significantly different from the 125 days seen in the IFN + cimetidine arm (p=0.87).

The authors conclude that the addition of cimetidine does not improve the activity of IFN in metastatic RCC.

J Cancer Res Oncol, 2006 Aug;132(8):499-504. Epub 2006 Apr 4