title: Immunotherapy of pulmonary metastatic renal cell carcinoma: success dependant on risk factors?
abstract: OBJECTIVE
  Risk factors may influence not only prognosis in metastic renal cell carcinoma but also probability of response to immunotherapy. Response of patients treated with inhalation of interleukin-2 (IL-2), which can be offered to those not suitable for systemic therapy, was compared to risk factors. We report on 116 patients who used inhaled IL-2 and were treated in different protocols with natural, recombinant glycosylated and recombinant non-glycosylated.
  
  
  METHODS
  All protocols had in common a high-dose inhalation of IL-2, either exclusively (11%), with low-dose systemic IL-2 (33%), or with low-dose systemic IL-2 and interferon-alpha (56%). Maximal toxicity per total treatment 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 with recombinant IL-2 (n=86). In all patients having risk factors the following 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 > or =2 (13%). In comparison, a group of patients having no risk factors at all was analyzed accordingly.
  
  
  RESULTS
  Response to immunotherapy is dependant on risk factors, the most prominent one being the ECOG. Patients with an ECOG > or =2 achieved no overall response compared to patients with no risk factors who responded to immunotherapy (33%). Progressive pulmonary metastases responded 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 response rate was 16%, 49%, and 35%, respectively. Median overall response duration was 9.6 months. Median achieved survival was 11.8 months (range: 1.7-68.8).
  
  
  CONCLUSIONS
  We conclude that risk factors have to be considered in the interpretation of response to immunotherapy. Exclusion of patients because of risk factors alone does not seem to be justified according to our data. Responses, including long-term stabilization, can be achieved in 27-57% of such patients. IL-2 immunotherapy can also be considered as useful antitumor therapy in patients with risk factors, especially if given without major toxicity.
authors.affiliation: Department of Urology, University of Hamburg, University Clinic Eppendorf, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Huland
authors.forename: H
authors.initials: H
authors.lastname: Heinzer
authors.forename: H
authors.initials: H
authors.lastname: Huland
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D005260:Female; D006031:Glycosylation; D006801:Humans; D007167:Immunotherapy; D016898:Interferon-alpha / Q000627:therapeutic use; D007376:Interleukin-2 / Q000009:adverse effects / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000401:mortality / Q000473:pathology*; D008175:Lung Neoplasms / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012307:Risk Factors; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D016898:Interferon-alpha; D007376:Interleukin-2; D011994:Recombinant Proteins