Daily subcutaneous ultra-low-dose interleukin 2 with daily low-dose interferon-alpha in patients with advanced renal cell carcinoma

A limited institution Phase II pilot study was performed using a very low-d ose combination of daily s.c. interleukin (IL)-2 with IFN-ol-ab in patients with advanced renal cancer in an attempt to duplicate or increase the resp onse documented with higher dose schedules without the attendant toxicity p rofile. We selected a dose of IL-2 with documented immunological activity a nd combined it with clinically active low-dose IFN, Between August 1994 and September 1996, 19 patients with metastatic renal cell carcinoma, who had been judged incapable of tolerating high-dose i.v. IL-2, were treated with IL-2 (1 million units/m(2)/day) and IFN (1 million units/day), administered s.c. daily. All treatments were administered on an outpatient basis. Virtu ally all patients had bulky tumor burden with multiple sites of involvement , including five patients with bone metastases, No major objective response s were observed; however, one patient experienced a minor response lasting 13 months, with an associated improvement in performance status. Median sur vival was 6 months, and 1-year survival was 16%, Toxicity was generally mil d and consisted almost entirely of constitutional symptoms. No serious grad e 3 or 1 toxicity was observed, although two patients withdrew from treatme nt due to treatment-related fatigue, On therapy, mild eosinophilia but no l ymphocytosis was noted; in fact, peripheral lymphocyte counts decreased, on ly to rebound after treatment was discontinued. No toxic deaths occurred. D espite the reasonable tolerability of this daily low-dose s.c. regimen, we conclude that this regimen is an ineffective treatment in metastatic renal cell carcinoma patients who are incapable of tolerating high-dose i.v. n-2.