High-dose IL-2 still preferred therapy for metastatic renal carcinoma

Despite its considerable toxicity, high-dose interleukin-2 (IL-2) remains the favored therapy for many patients with metastatic renal cell cancer, according to findings from a phase III trial. For certain subgroups, however, a less toxic regimen involving subcutaneous IL-2 plus interferon may be a suitable alternative.

High-dose IL-2 has proven to be an effective treatment for metastatic renal cell carcinoma since its approval in 1992. However, due to its toxic effects, regimens involving lower doses of IL-2 have been developed.Treatment with a lower dose of IL-2, given subcutaneously, plus interferon has shown promise in phase II studies, but until now, it had not been evaluated in a randomized trial.As reported in the Journal of Clinical Oncology for January 1st, Dr. David F. McDermott, from Beth Israel Deaconess Medical Center in Boston, and colleagues assessed the outcomes of 192 patients who were randomized to receive high-dose IL-2 or subcutaneous IL-2 plus interferon. The treatment response rate with high-dose IL-2 was 23.2%, significantly higher than the 9.9% rate seen in the subcutaneous IL-2/interferon group (p = 0.018). Still, in terms of the primary endpoint, progression-free survival at 3 years, the groups were not significantly different; 10 patients treated with high-dose IL-2 and three treated with the combination regimen achieved this endpoint (p = 0.082).Median response durations and median survival periods were also not significantly different between the groups in the overall analysis. However, for patients with bone or liver metastases or a primary tumor in place, high-dose IL-2 was tied to significantly better survival than subcutaneous IL-2/interferon. As anticipated, high-dose IL-2 was more toxic than the combination regimen. However, this did not seem to impact overall quality of life. “Interestingly, quality of life with the high-dose treatment is worse initially, but over time it tends to equalize” with that of the combination regimen, Dr. McDermott told Reuters Health.”The most important message from this study is that high-dose IL-2 is the preferred treatment for many, but not all, patients” with metastatic renal cell carcinoma, Dr. McDermott said. “We’re getting closer to figuring out who should and shouldn’t get it and we’re now looking at tumor histology and tumor markers as a way to guide patient selection.”So who are candidates for the less toxic subcutaneous IL-2/interferon regimen? Dr. McDermott said that “patients with a good performance status and metastases to only their lungs, for example, responded just as well to this regimen as they did to high-dose IL-2 and their survival was not compromised.” (Source: J Clin Oncol 2005;23:133-141: Reuters Health: Anthony J. Brown, MD: Oncolink: January 2005.)