title: A randomized study of immunotherapy with low-dose subcutaneous interleukin-2 plus melatonin vs chemotherapy with cisplatin and etoposide as first-line therapy for advanced non-small cell lung cancer.
abstract: OBJECTIVE
  The therapeutic role of chemotherapy in advanced non-small cell lung cancer (NSCLC) is controversial because of its potentially detrimental action on host anticancer defenses. On the contrary, IL-2 would seem to prolong survival time by improving the immune status, even though it is generally less effective in determining tumor regression in NSCLC. Our previous studies have suggested the possibility of increasing tumor sensitivity to IL-2 by concomitant administration of immunomodulating neurohormones, such as the pineal hormone melatonin (MLT). On this basis, a study was carried out to evaluate the efficacy of immunotherapy with low-dose IL-2 plus MLT versus chemotherapy in advanced NSCLC.
  
  
  METHODS
  The study included 60 patients with locally advanced or metastatic NSCLC, who were randomized to receive immunotherapy or chemotherapy. The immunotherapy consisted of IL-2 (3 million IU/day subcutaneously for 6 days/week for 4 weeks) and MLT (40 mg/day orally every day, starting 7 days before IL-2); in nonprogressing patients, a second cycle was repeated after a 21-day rest period, then they underwent a maintenance period consisting of one week of therapy every month until progression. Chemotherapy consisted of cisplatin (20 mg/m2) and etoposide (100 mg/m2)/day intravenously for 3 days; cycles of chemotherapy were repeated every 21 days until progression.
  
  
  RESULTS
  No complete response was obtained. A partial response was achieved in 7/29 patients treated with chemotherapy and in 6/31 patients receiving chemotherapy. The difference was not significant. In contrast, the mean progression-free period and the percentage survival at 1 year was significantly higher in patients treated with immunotherapy than in those treated with chemotherapy. Toxicity was substantially lower in patients receiving immunotherapy than in those given chemotherapy.
  
  
  CONCLUSIONS
  This randomized study showed that immunotherapy with low-dose IL-2 plus MLT is a better tolerated and more effective therapy in terms of survival time than chemotherapy containing cisplatin in patients affected by advanced NSCLC.
authors.affiliation: Divisione di Radioterapia Oncologica, Ospedale San Gerardo, Monza, Milano, Italia.
authors.forename: P
authors.initials: P
authors.lastname: Lissoni
authors.forename: S
authors.initials: S
authors.lastname: Meregalli
authors.forename: V
authors.initials: V
authors.lastname: Fossati
authors.forename: F
authors.initials: F
authors.lastname: Paolorossi
authors.forename: S
authors.initials: S
authors.lastname: Barni
authors.forename: G
authors.initials: G
authors.lastname: Tancini
authors.forename: F
authors.initials: F
authors.lastname: Frigerio
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D002945:Cisplatin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects / Q000379:methods*; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000008:administration & dosage; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D008297:Male; D008550:Melatonin / Q000008:administration & dosage; D008875:Middle Aged; D009367:Neoplasm Staging; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D007376:Interleukin-2; D005047:Etoposide; D008550:Melatonin; D002945:Cisplatin