TREATMENT OF PATIENTS WITH METASTATIC RENAL-CELL CARCINOMA WITH SUBCUTANEOUS RECOMBINANT INTERFERON-ALPHA-2B AND CONTINUOUS-INFUSION OF RECOMBINANT INTERLEUKIN-2 - A PHASE-II STUDY

Background: On the basis of encouraging preclinical data, we investigated the combination of the 2 agents recombinant interferon-alpha 2b (IFN-alpha) and recombinant interleukin-2 (rIL-2) in the treatment of patients with metastatic renal cell carcinoma in the hope of finding evidence of an increase in therapeutic efficacy, with an acceptable toxicity profile in comparison to the single substances. Patients and Methods: In a multicenter phase II study, 23 patients with metastatic renal cell cancer were treated with a combination of rIL-2 (Proleukin(R), EuroCetus), administered by continuous infusion at a dose of 18 Mio IU/m(2)/d on days 1-5 and 8-12 and IFN-alpha (Intron-A(R), Schering-Plough) at 6 Mio IU/m(2)/d on days 1, 3, 5, 8, 10 and 12. After a rest period of 2 weeks the treatment was repeated. Results: Five complete remissions (CRs) and 2 partial remissions (PRs) were observed, with a total response rate of 30%. All CRs occurred in patients with lung metastases. Durable CRs were observed in 2 patients, without maintenance therapy for now 42+ and 49+ months. Toxicity was usually manageable on a routine medical ward. Grade IV hypotension was observed in 2 patients and there was 1 case of colonic perforation and 1 case of fatal pulmonary embolism. Conclusions: In the present phase II study, combination treatment with rIL-2+IFN-alpha was found to be an active although toxic regimen.