title: A randomized trial of adoptive immunotherapy with tumor-infiltrating lymphocytes and interleukin-2 versus standard therapy in the postoperative treatment of resected nonsmall cell lung carcinoma.
abstract: BACKGROUND
  A previous pilot study from our group suggested that: (1) adoptive immunotherapy (A1) with tumor-infiltrating lymphocytes (TIL) and recombinant interleukin-2 (rIL-2) may be applied with safety to more than 80% of the patients who had surgery for Stage III nonsmall cell lung carcinoma (NSCLC); and (2) AI could be useful in patients with locally advanced disease. The present randomized study was planned to assess the efficacy of AI in the postoperative treatment of Stage II, IIIa, or IIIb NSCLC:
  
  
  METHODS
  TIL were expanded in vitro from tissue samples obtained from the surgically removed specimens of 131 patients. Eighteen cultures yielded no growth of TIL. The remaining 113 patients were stratified according to disease stage and randomized to receive AI or standard chemoradiotherapy. TIL were infused intravenously 6 to 8 weeks after surgery, rIL-2 was administered subcutaneously at escalating doses for 2 weeks, and then at reduced doses for 2 weeks and then for 2 to 3 months.
  
  
  RESULTS
  Three-year survival was significantly better (P < 0.05) for patients who underwent AI than for controls. AI was of no benefit to patients with Stage II NSCLC, potentially useful to patients with Stage IIIa NSCLC (P = 0.06), and significantly advantageous to patients with Stage IIIb (T4) NSCLC (P < 0.01). For patients with Stage III NSCLC, local relapse (but not distant relapse) was significantly reduced following AI (P < 0.05).
  
  
  CONCLUSIONS
  AI should be considered when designing future adjuvant therapy protocols for the treatment of NSCLC:
authors.affiliation: Istituto Patologia Chirurgica, University of Genoa, Italy.
authors.forename: G B
authors.initials: GB
authors.lastname: Ratto
authors.forename: P
authors.initials: P
authors.lastname: Zino
authors.forename: S
authors.initials: S
authors.lastname: Mirabelli
authors.forename: P
authors.initials: P
authors.lastname: Minuti
authors.forename: R
authors.initials: R
authors.lastname: Aquilina
authors.forename: G
authors.initials: G
authors.lastname: Fantino
authors.forename: E
authors.initials: E
authors.lastname: Spessa
authors.forename: M
authors.initials: M
authors.lastname: Ponte
authors.forename: P
authors.initials: P
authors.lastname: Bruzzi
authors.forename: G
authors.initials: G
authors.lastname: Melioli
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D003131:Combined Modality Therapy; D005500:Follow-Up Studies; D006801:Humans; D016219:Immunotherapy, Adoptive; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000473:pathology / Q000517:prevention & control; D009367:Neoplasm Staging; D018365:Neoplasm, Residual; D011013:Pneumonectomy; D011182:Postoperative Care; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D007376:Interleukin-2