Cancer test bed
For patients with renal cell carcinoma, few treatment options exist beyond surgical removal of the kidney. The only approved drug for metastatic RCC is Proleukin aldesleukin, a recombinant version of interleukin-2 from Chiron Corp. (CHIR, Emeryville, Calif.), but its efficacy is limited and side effects can be severe. The same poor performance is shown by interferon alpha, which is used off label.
As a result, the disease is an attractive target for companies developing cancer treatments, and the variety of approaches provides a microcosm of cancer therapy trends. More than a dozen companies have reached Phase II and III trials, and the first approval could come early next year in Europe.
Room for improvement
Worldwide, 180,000 new cases are diagnosed each year, according to the NCI. In Europe and the U.S., RCC causes 33,500 deaths per year, and the incidence is increasing.
The five-year survival rate is about 60% for all patients diagnosed with RCC across all stages, with treatment typically involving nephrectomy followed by one of the cytokines. It is about 90% for those whose tumor is confined to the kidney, and about 60% if it has only spread to nearby tissues. Patients who develop metastases usually have a life expectancy of 6-10 months, with three- and five-year survivals of 4.4% and 1.7%(see "Staging RCC," A2).
For the approved treatment, IL-2, the response rate was 15% in several multicenter trials. A high-dose regimen resulted in a 19% response rate with 5% complete responses. According to the product labeling, the majority of responses to IL-2 were durable, with median response duration of 20 months for partial and more than 80 months for complete responses.
According to the literature, 80% of patients who responded completely to therapy with IL-2 were alive at 10 years.
But the toxic effects associated with high-dose IL-2 are related to increased vascular permeability and require in-patient monitoring, often in an intensive care unit. The major toxic effect of high-dose IL-2 is a sepsis-like syndrome; others are fever, hypotension, chills and fatigue. Moreover, high-dose IL-2 has been associated with a 1-4% incidence of treatment-related