3047 Background: The aim of this study was to evaluate the activity and toxicity of a multistep, sequential treatment including induction chemotherapy (ICT), consolidation chemoradiotherapy (CXRT), and maintenance immunotherapy (MI) in untreated patients with locally advanced (LA), inoperable, or incompletely resected Pa and Bt ADK. MI with low-dose interleukin-2 (IL-2) and 13-cis-retinoic acid (RA) was given in order to enhance the immune function, which could eradicate minimal residual disease, as previously shown (Clin Cancer Res 2001). Methods: From September 2003 to September 2007, 54 patients, 32 men, 22 women, 63% with Pa and 37% with Bt ADK, mean age of 63 years (range 36–75), were treated with an ICT consisting of 3 courses of cisplatin, 70 mg/m2 day 1, gemcitabine 1000 mg/m2 day 1 and 8 every 3 weeks. Patients who were progression-free (PF) after ICT received CXRT, 45 Gy in 25 fractions, using coplanar four-field technique, with concurrent capecitabine 850 mg/m2/day. Six weeks after completion of CXRT, patients were restaged: In the absence of disease progression, they received, as an MI, IL-2, 1.8 x 106 I.U. and RA, 5 mg/kg, 5 days/week, 3 weeks/month for 1 year and thereafter until progression. Results: After a median follow-up of 27.5 months, all patients were evaluable. A response rate of 26% (95% c.i. 15–40%), was observed, with 44.5% of patients achieving stable disease. Thirty-eight patients, 27 with Pa and 11 with Bt ADK, had a clinical benefit from ICT, and were treated with CXRT. Fourteen PF patients, 7 Pa and 7 Bt ADK, received an MI with IL-2 and RA. Median progression-free survival (PFS) and overall survival (OS) for all 54 patients were 6.8 and 12.1 months, respectively, while the 14 patients treated with MI had a 5-year PFS and OS rate of 36% and 58%, respectively. Grade 3–4 hematological and gastrointestinal toxicity were observed in 30% and 37% of patients, respectively, while 28% of patients had grade 1–2 autoimmune reactions. Conclusions: These results support the efficacy and safety of a multistep sequential treatment with ICT, followed by CXRT, and an MI with IL-2 and RA, in patients with LA, inoperable or incompletely resected Pa and Bt ADK. Further studies are necessary to validate this strategy. No significant financial relationships to disclose.