Therapeutic approaches in metastatic renal cell carcinoma: local immunotherapy.
Since 1990, aerosol interleukin (IL)-2 has been used to treat pulmonary metastatic renal cell carcinoma (pmRCC). Inhalation therapy deposits a drug into the airways to achieve a high, local, clinical effect while avoiding serious systemic side effects. We report three studies to describe safety and efficacy of aerosol IL-2 in patients with pmRCC. In a multicenter study, 24 patients received exclusive inhalation (study I) of natural IL-2 (three dose levels, 48 weeks) and response and toxicity were evaluated. The survival of high-risk patients (study II) with mainly inhaled IL-2 (n=94) was compared with that of patients receiving systemic IL-2 (n=103). In ten patients we analyzed in detail lung function and markers of airway inflammation before and during inhalational IL-2 therapy (study III). Study I: The response of exclusive inhalation was 33.3% at 3 months and 16.7% at 6 months. Treatment was well tolerated, cough being the most frequent adverse event. Study II: The probabilities of survival at 5 years were 21% for the inhalational group and 0% for the systemic group. Study III: Inhaled IL-2 induced a moderate decline of forced expiratory volume (FEV), while exhaled nitric oxide (NO) and sputum eosinophils rose accompanied by moderate cough and dyspnea. In conclusion, inhalational IL-2 combines good efficacy and improves tolerability. This is especially important for patients who are not able to benefit from systemic IL-2 therapy. Whether the local eosinophilic response additionally supports the antitumor effect remains a challenging question.
Huland
Edith
E
Department of Urology, University Hospital Hamburg-Eppendorf, Hamburg, Germany. huland@uke.uni-hamburg.de
Heinzer
H
H
Jörres
R A
RA
Loppow
D
D
Huland
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D000280:Administration, Inhalation; D000328:Adult; D000336:Aerosols; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000556:secondary*; D018849:Controlled Clinical Trials as Topic; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000009:adverse effects; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis
D000336:Aerosols; D000970:Antineoplastic Agents; D007376:Interleukin-2