title: Gefitinib plus interleukin-2 in advanced non-small cell lung cancer patients previously treated with chemotherapy.
abstract: The activation of lymphocytes by gefitinib treatment has been described. In this phase II pilot trial, we explored the possible synergism between IL-2 and gefitinib for non-small cell lung cancer (NSCLC) treatment. From September, 2003, to November, 2006, 70 consecutive patients with advanced, progressive NSCLC, previously treated with chemotherapy, received oral gefitinib 250 mg daily. The first 39 patients received gefitinib alone (G group). The other 31 also received subcutaneous IL-2 (GIL-2 group): 1 MIU/m2 (Million International Unit/m2)twice a day on Days 1 and 2, once a day on Days 3, 4, 5 every week for four consecutive weeks with a four-week rest period. Median follow-up was 25.2 months. Grade 3-4 toxicity of gefitinib was represented by skin rash (7%), asthenia/anorexia (6%) and diarrhea (7%); patients treated with IL-2 showed grade 2-3 fever (46%), fatigue (21%) and arthralgia (13%). In the GIL-2 group and G-group, we respectively observed: an overall response rate of 16.1% (6.4% complete response) and 5.1% (only partial response); a disease control rate of 41.9% and 41%; a median time to progression of 3.5 (CI 95% = 3.2-3.8) and 4.1 (CI 95% = 2.6-5.7) months; a median overall survival of 20.1 (CI 95% = 5.1-35.1) and 6.9 (CI 95% = 4.9-8.9) months (p = 0.002); and an actuarial one-year survival rate of 54% and 30%. Skin toxicity (p < 0.001; HR = 0.29; CI 95% = 0.16-0.54) and use of IL-2 (p < 0.001; HR = 0.33; CI 95% = 0.18-0.60) were independently associated with improvement of survival. In this consecutive, non-randomized, series of advanced NSCLC patients, the use of IL-2 increased the efficacy of gefitinib.
authors.affiliation: Oncology Unit, University Hospital of Parma, Via Gramsci, 14, 43126 Parma, Italy. melissa.bersanelli@alice.it.
authors.forename: Melissa
authors.initials: M
authors.lastname: Bersanelli
authors.affiliation: Oncology Unit, University Hospital of Parma, Via Gramsci, 14, 43126 Parma, Italy. sebabuti@libero.it.
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Buti
authors.affiliation: Oncology Unit, University Hospital of Parma, Via Gramsci, 14, 43126 Parma, Italy. rcamisa@ao.pr.it.
authors.forename: Roberta
authors.initials: R
authors.lastname: Camisa
authors.affiliation: Oncology Unit, Azienda Istituti Ospitalieri di Cremona, Largo Priori, 1, 26100 Cremona, Italy. m.brighenti@ospedale.cremona.it.
authors.forename: Matteo
authors.initials: M
authors.lastname: Brighenti
authors.affiliation: Oncology Unit, Azienda Istituti Ospitalieri di Cremona, Largo Priori, 1, 26100 Cremona, Italy. s.lazzarelli@ospedale.cremona.it.
authors.forename: Silvia
authors.initials: S
authors.lastname: Lazzarelli
authors.affiliation: Radiology Division, Spedali Civili di Brescia, P.le Spedali Civili,1, 25123 Brescia, Italy. radiologia1@spedalicivili.brescia.it.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Mazza
authors.affiliation: Oncology Unit, Azienda Istituti Ospitalieri di Cremona, Largo Priori, 1, 26100 Cremona, Italy. r.passalacqua@ospedale.cremona.it.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Passalacqua