PHASE-III RANDOMIZED TRIAL OF INTERLEUKIN-2 WITH OR WITHOUT LYMPHOKINE-ACTIVATED KILLER-CELLS IN THE TREATMENT OF PATIENTS WITH ADVANCED RENAL-CELL CARCINOMA

Background. Treatment with interleukin-2 (IL-2) and lymphokine-activat ed killer cells (LAK) resulted in responses in some patients with adva nced renal cell carcinoma (RCC). However, the relative therapeutic ben efit of the addition of LAK to IL-2 was unknown. Methods. A randomized Phase III trial was conducted in patients with RCC comparing continuo us intravenous infusion (CI) IL-2 alone with CI IL-2 plus LAK. Interle ukin-2 was administered at 3 X 10(6) U/m(2)/day on days 1-5, 13-17, 21 -24, and 28-31. Patients on the LAK treatment arm underwent leukaphere sis on days 8-10 and LAK cell reinfusion on days 13-15. The results ar e reported with long-term follow-up. The published experience with IL- 2 alone or with the addition of LAK was investigated in a quantitative literature survey. The response proportions were studied by schedule (high dose bolus, moderate dose, low dose) and by concomitant administ ration of LAK. Results. Seventy-one patients were treated, 36 on the I L-2 arm and 35 on the IL-2 plus LAK arm. Four patients (6%) had major responses (two complete, two partial). The median survival of all pati ents was 13 months (95% confidence interval [CI], 9-18 months). There were no differences between treatment arms with regard to response (P = 0.61) and survival (P = 0.67). More patients on the LAK arm experien ced pulmonary toxicity (P = 0.008). The overall weighted response prop ortion was 16% (95% CI, 8%-24%) for the 39 published series of 1291 pa tients treated with 1L-2. The 95% confidence intervals for response pr oportion overlapped when compared by schedule and by administration of LAK. Conclusions. The dose and schedule of IL-2 used in this study re sulted in a low level of antitumor activity and the addition of LAK di d not improve the response rate against RCC. Given the infrequent, but reproducible, responses with IL-2 and interferon-based regimens, cont inued investigation of these agents is warranted as is the study of ne w cytokines. Alternative treatment strategies should be studied in RCC and new agents and treatment regimens that appear promising in Phase II studies must be studied in randomized trials.