MULTIINSTITUTIONAL HOME-THERAPY TRIAL OF RECOMBINANT HUMAN INTERLEUKIN-2 AND INTERFERON ALFA-2 IN PROGRESSIVE METASTATIC RENAL-CELL CARCINOMA

Purpose: In a phase II multiinstitutional outpatient trial, patients w ith progressive metastatic renal cell carcinoma were treated with a co mbination of subcutaneous (SC) recombinant interleukin-2 (rIL-2) and r ecombinant interferon alfa-2 (rIFN alpha 2). Patients and Methods: One hundred fifty-two patients with metastatic renal cell carcinoma were treated. Treatment courses consisted of SC rIL-2 at 20 x 10(6) IU/m(2) three times per week in weeks 1 and 4, and at 5 x 10(6) IU/m(2) three times per week in weeks 2, 3, 5, and 6. Additionally, patients receiv ed SC rIFN alpha 2 6 x 10(6) U/m(2) once per week in weeks 1 and 4, an d three times per week in weeks 2, 3, 5, and 6. Results: There were ni ne (6%) complete responses (CRs) and 29 (19%) partial responses (PRs), for an overall response rate of 25% (95% confidence interval, 19% to 32%). The median duration of responses for CRs and PRs was 16+ and 9 m onths, respectively. Additionally, 55 patients (36%) had stable diseas e (SD). Fifty-nine patients (39%) had continued disease progression (P D) despite treatment, or went off study after less than 4 weeks of the rapy. The majority of patients treated experienced fever, chills, mala ise, nausea, vomiting, and anorexia, side effects that were mostly lim ited to World Health Organization (WHO) grade 1 and 2. However, one pa tient developed grade 4 CNS toxicity with extended somnolence. On cess ation of therapy, the neurologic symptoms in this patient were fully r eversible, with no neurologic deficiency. Conclusion: In summary, this multiinstitutional home-therapy setting of SC rIL-2 and SC rIFN alpha 2 in patients with progressive metastatic renal cell carcinoma demons trated drastically reduced systemic toxicity, while it confirmed the t herapeutic efficacy of the low-dose SC immunotherapy combination sched ule.