A progress report on the outpatient treatment of patients with advanced renal cell carcinoma using subcutaneous recombinant interleukin-2.

In an attempt to increase the therapeutic index of IL-2 based immunotherapy, the efficacy and toxicity of subcutaneous IL-2 was studied in forty-seven patients, mean age 59 years (range 42-76), with advanced renal cell carcinoma (RCC). IL-2 was administered by subcutaneous injection at 18x10 IU daily for 5 days. After the first weekly cycle the dose in the first two days was reduced to 9x10 IU. Patients were treated for 4 or 6 consecutive weeks. Two 6week cycles or three 4-week cycles were given maximally. Fourteen patients in this study where 65 years or older. Twenty-one patients had concomitant disease that would probably render them not eligible for intravenous IL-2 treatment. Forty-six patients were evaluable for response. One patient died of a myocardial infarction after 3 week treatment. Nine responses were observed, two complete and seven partial. Four out of the nine responding patients were 65 years or older. Response durations were 35+, 29, 28+, 21+, 11, 8, 3+, 2, 1+ months. The median survival of all patients was 12 months, whereas the median survival of both nonresponders and responders was 10 and 37+ months, respectively (P= 0.025). The main toxicity consisted of local inflammation and induration at the injection sites, flu like symptoms with fever, nausea/vomiting and diarrhoea. None of these side effects required hospitalization, and they were acceptable even in patients with concomitant disease. Subcutaneous IL-2 therapy is active and has limited toxicity in patients with advanced RCC. This outpatient regimen renders immunotherapy applicable in older patients and patients with concomitant disease. Subcutaneous IL-2 therapy is attractive to combine with other treatment modalities like monoclonal antibodies, interferon or chemotherapy.