Chemotherapy with or without low-dose interleukin-2 in advanced non-small cell lung cancer: Results from a phase III randomized multicentric trial

Laura Ridolfi, Oscar Bertetto, Antonio Santo, Emanuele Naglieri, Massimo Lopez, Francesco Recchia, Paolo Lissoni, Marco Galliano, Franco Testore, Camillo Porta, Monica Maglie, Monia Dall'Agata, Luca Fumagalli, Ruggero Ridolfi

Research output: Contribution to journalArticlepeer-review


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/m 2) on days 1 and 8 + cisplatin (100 mg/m 2) 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.

Original languageEnglish
Pages (from-to)1011-1017
Number of pages7
JournalInternational Journal of Oncology
Issue number4
Publication statusPublished - Oct 2011


  • Chemotherapy
  • Combination therapy
  • Low-dose IL-2

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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