PHASE-II TRIAL OF RECOMBINANT INTERLEUKIN-1-BETA IN PATIENTS WITH METASTATIC RENAL-CELL CARCINOMA

Interleukin-1 (IL-1) plays a central role in the immune system, partly by stimulating the production of interleukin-2 (IL-2) and other cytok ines by lymphocytes. In preclinical studies, recombinant interleukin-1 (rIL-1 beta) has shown antitumor activity. We conducted a phase II tr ial to evaluate the efficacy of rIL-1 in metastatic renal cell carcino ma (RCC). rIL-1 beta was given at a dose of 50 ng/kg i.v. daily for 5 days on a 28-day schedule. Nineteen patients were registered; 16 compl eted two cycles and were evaluable for response. There were no complet e or partial responses to treatment. Toxicity was generally mild and t ypically involved grades I and II fever, rigors, hypotension, and weig ht gain. Severe neurologic toxicity was seen in two patients, grade IV seizures were seen in one, and grade III somnolence was seen in anoth er. Analysis of soluble IL-2 receptor (sIL-2r) levels revealed an incr ease from a mean pretreatment level of 4,567 pg/ml to a mean of 6,124 pg/ml posttreatment (p < 0.001). The mean pretreatment IL-6 level was 51 pg/ml, increased to 84 pg/ml posttreatment (p < 0.05). Patients wit h bulky disease had higher sIL-2r levels, and patients with tumor feve rs had higher IL-6 and sIL-2r levels than patients without fever did. A neutrophilic leukocytosis and a mild thrombocytosis were observed in response to rIL-1 beta administration. We conclude that rIL-1 beta in this dose and schedule is inactive in metastatic RCC.