INTERLEUKIN-2-BASED THERAPY FOR METASTATIC RENAL-CELL CANCER - THE CYTOKINE WORKING GROUP EXPERIENCE, 1989-1997

PURPOSE This article reviews long-term follow-up data from three phase II studies conducted by the Cytokine Working Group from 1989 to 1995 that evaluated various recombinant interleukin-2 (rIL-2)-based regimen s in patients with metastatic renal cell cancer. Response rates, longt erm response duration, and toxicity are compared. PATIENTS AND METHODS The Cytokine Working Group studies reviewed here investigated the saf ety and efficacy of two high-dose intravenous rIL-2-based regimens and two moderate-dose outpatient subcutaneous rIL-2-based regimens in pat ients with progressive metastatic renal cell cancer. A randomized phas e II study, initiated in 1989, investigated the safety and efficacy of high-dose intravenous rIL-2 alone and high-dose intravenous rIL-2 plu s recombinant interferon-alpha (rIFN-alpha). A second phase II study, initiated in 1992, tested the safety and efficacy of moderate-dose sub cutaneous rIL-2 plus subcutaneous rIFN-alpha in the outpatient setting . The third trial, initiated in 1995, investigated a regimen consistin g of the previous subcutaneous rIL-2 plus rIFN-alpha regimen alternati ng with intravenous bolus 5-fluorouracil (5-FU) plus subcutaneous rIFN -alpha. Median follow-up for these studies is 72 months, 48 months, an d 24 months, respectively. RESULTS The overall response rates observed with each of these regimens were similar (17% with high-dose rIL-2 al one, 11% with high-dose rIL-2/rIFN-alpha, 17% with outpatient subcutan eous rIL-2/rIFN-alpha, and 16% with outpatient rIL-2/rIFN-alpha, plus 5-FU/rIFN-alpha). However, the high-dose rIL-2 regimen produced a 7% c omplete response rate, compared with 0%, 4%, and 4%, respectively with each of the other regimens. Median response duration was also much lo nger with high-dose intravenous rIL-2 alone (53 months), compared with 7 months, 12 months, and 9 months, respectively, with each of the oth er regimens. CONCLUSION Complete response rate and response duration a ppear to favor the high-dose intravenous rIL-2 regimen. This will requ ire verification in a randomized study comparing the bst high-dose arm (rIL-2 alone) with the best outpatient regimen (rIL-2/IFN-alpha). The Cytokine Working Group is currently conducting such a study.