Immunotherapy of pulmonary metastatic renal cell carcinoma: Success dependant on risk factors?

BACKGROUND/AIMS: Risk factors may influence not only prognosis in metastic renal cell carcinoma but also probability of response to immunotherapy. Res ponse of patients treated with inhalation of interleukin-2 (IL-2), which ca n be offered to those not suitable for systemic therapy, was compared to ri sk factors. We report on 116 patients who used inhaled IL-2 and were treate d in different protocols with natural, recombinant glycosylated and recombi nant non-glycosylated, METHODOLOGY: All protocols had in common a high-dose inhalation of IL-2, ei ther exclusively (11%), with low-dose systemic IL-2 (33%), or with low-dose systemic IL-2 and interferon-alpha (56%). Maximal toxicity per total treat ment time (median treatment time: 7.2 months) was mild and there was a low incidence (16%) of WHO grade 3 toxicity. Treatment response was analyzed in a subgroup of patients having at least one given risk factor and treated w ith recombinant IL-2 (n=86). In all patients having risk factors the follow ing distribution was found: more than 1 metastic location (86%), diagnosis to treatment interval (DTI) <12 months (62%), weight loss prior to therapy (41%), and ECOG performance status greater than or equal to 2 (13%). In com parison, a group of patients having no risk factors at all was analyzed acc ordingly. RESULTS: Response to immunotherapy is dependant on risk factors, the most p rominent one being the ECOG. Patients with an ECOG greater than or equal to 2 achieved no overall response compared to patients with no risk factors w ho responded to immunotherapy (33%). Progressive pulmonary metastases respo nded in 15% of patients for a median of 15.5 months (range: 4.133) and were stabilized in 55% for a median of 6.6 months (range: 3-51.7). Overall resp onse rate was 16%, 49%, and 35%, respectively. Median overall response dura tion was 9.6 months. Median achieved survival was 11.8 months (range: 1.7-6 8.8). CONCLUSIONS: We conclude that risk factors have to be considered in the int erpretation of response to immunotherapy. Exclusion of patients because of risk factors alone does not seem to be justified according to our data. Res ponses, including long-term stabilization, can be achieved in 27-57% of suc h patients. IL-2 immunotherapy can also be considered as useful antitumor t herapy in patients with risk factors, especially if given without major tox icity.