title: Chemotherapy with or without low-dose interleukin-2 in advanced non-small cell lung cancer: results from a phase III randomized multicentric trial.
abstract: Non-small cell lung cancer (NSCLC) is associated with IL-2-dependent cell-mediated immunodeficiency. As IL-2 is the main lymphocyte growth factor, a phase III randomized multicenter trial was conducted to evaluate the impact of subcutaneous low-dose IL-2 added to standard chemotherapy (CT) on overall survival (OS) in advanced NSCLC patients. Patients (n=241) with histologically confirmed stage IIIb or IV non-operable NSCLC underwent stratified randomization on the basis of center, ECOG PS, stage of disease and percentage of weight loss. Patients received gemcitabine (1000 mg/m2) on days 1 and 8 + cisplatin (100 mg/m2) on day 2 every 21 days for a maximum of 6 cycles [chemotherapy (CT) arm]. In the CT+IL-2 arm, patients also received low-dose subcutaneous IL-2 3,000,000 IU/die on days 3-5, 9-11, 15-17. The study had 90% power to detect a 20% absolute increase in 1-year OS with 118 patients/arm. An overall response (OR) rate of 12.8% (14% in the CT+IL-2 arm and 11.4% in CT arm) was observed. Stable disease was 70 and 66.7%, and progressive disease 16 and 21.8% in the CT+IL-2 and CT arms, respectively. No differences in response were found in any subgroup analysis. At a median follow-up of 32 months, 1-year OS was 45% for the CT+IL-2 arm vs. 51% for the CT arm (p=0.456 log-rank). Median progression-free survival was 6.6 months in the CT+IL-2 arm vs. 6.9 months in the CT arm (p=0.573, log-rank). A higher number of grade 4 toxicities were reported with CT+IL-2. The most common grade ≥3 adverse events were gastrointestinal toxicity (mainly nausea and diarrhea) and myelosuppression. No relevant differences in clinical outcome were observed from the addition of IL-2 to CT. Future studies investigating the role of T-regulators in chemoimmunotherapeutic regimens could be performed.
authors: Immunotherapy Unit, I.R.S.T., Via P. Maroncelli 40, 47014 Meldola (FC), Italy. l.ridolfi@irst.emr.it
authors: Laura
authors: L
authors: Ridolfi
authors: Oscar
authors: O
authors: Bertetto
authors: Antonio
authors: A
authors: Santo
authors: Emanuele
authors: E
authors: Naglieri
authors: Massimo
authors: M
authors: Lopez
authors: Francesco
authors: F
authors: Recchia
authors: Paolo
authors: P
authors: Lissoni
authors: Marco
authors: M
authors: Galliano
authors: Franco
authors: F
authors: Testore
authors: Camillo
authors: C
authors: Porta
authors: Monica
authors: M
authors: Maglie
authors: Monia
authors: M
authors: Dall'agata
authors: Luca
authors: L
authors: Fumagalli
authors: Ruggero
authors: R
authors: Ridolfi
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; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D060046:Maintenance Chemotherapy; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D009367:Neoplasm Staging / Q000379:methods; D000093542:Gemcitabine
chemical_list: D007376:Interleukin-2; D003841:Deoxycytidine; D002945:Cisplatin; D000093542:Gemcitabine