CONCOMITANT ADMINISTRATION OF RECOMBINANT HUMAN INTERLEUKIN-2 AND RECOMBINANT INTERFERON ALFA-2A - AN ACTIVE OUTPATIENT REGIMEN IN METASTATIC RENAL-CELL CARCINOMA

Purpose: A phase II trial of interleukin-2 (IL-2) and interferon alfa (IFN-α) in metastatic renal cell carcinoma (RCCa) was conducted. A lower dosage of IL-2 was given via continuous intravenous (IV) infusion, a route with documented tumor activity associated with less toxicity, with the purpose of improving the therapeutic index of this treatment in an outpatient setting. Patients and Methods: Thirty patients with metastatic RCCa were treated with the combination of IL-2 and IFN-α-2A. IL-2 was administered on days 1 through 4 of each treatment week, as a continuous IV infusion at a dose of 2 x 106 U/m2/d. IFN-α-2A was administered intramuscularly or subcutaneously on days 1 and 4 of each treatment week, at a dose of 6 x 106 U/m2/d. One treatment course included 4 weeks of treatment followed by a 2- week rest. Patients received therapy as outpatients except for the first 4 days of treatment, cycle 1 only. All patients were assessable for toxicity and response assessment. A total of 105 courses of therapy were administered, 51% at full dose. Results: Sixteen patients experienced toxicities resulting in dosage modification. The major treatment-limiting toxicities were gastrointestinal, neurologic, and fatigue. Nine patients (30%) had partial remissions (PRs) with a median duration of responses of 12+ months. The median time to response was 11 weeks. Two partial responders whose sites of metastatic disease were renal fossa and mediastinal lymph nodes (LN), respectively, were found to have achieved a pathologic complete remission (pCR) after surgery. A third patient with a pCR of axillary LN was rendered into a surgical complete remission (sCR) with salvage nephrectomy. Median survival of patients obtaining a PR has not been reached with a median follow-up time of 19+ months. Conclusion: IL-2 and IFN-α-2A is well tolerated in the outpatient treatment setting and demonstrates significant clinical activity against RCCa.