Bortezomib In Combination With Gemicitabine (Gem) And Cisplatin (Cddp)) In Patients With Locally Advanced/Metastatic Non-Small Cell Lung Cancer (Nsclc): A Hellenic Oncology Research Group Multicenter Phase 11 Study.

e19050 Background: Bortezomib, is a selective reversible proteasome inhibitor with proapoptotic effects. A multicenter phase II study of bortezomib in combination with GEM and CDDP in advanced NSCLC was conducted. Methods: Patients (pts) with inoperable stage IIIB or IV NSCLC, who had not received previous chemotherapy for advanced disease, were administered bortezomib 1 mg/m2 on days 1 and 8, and starting from cycle 2, bortezomib (as described previously) in combination with GEM 1,000 mg/m2, days 1, 8, and CDDP 70 mg/m2, day 1; treatment was repeated every 21-days. Up to 8 cycles of combination therapy could be administered; single-agent bortezomib was continued until disease progression or unacceptable toxicity. Results: Fifty- three pts (median age, 66 years; 79.2% male; 96.2% stage IV; performance status 0/1 73.6%/26.4%; adenocarcinoma 39.6%, squamous cell carcinoma 41.5%, were enrolled. All pts were evaluable for toxicity and 44 for efficacy analysis. Grade 3-4 hematologic toxicity consisted of neutropenia (22.6%) and thrombocytopenia (17%). More common non-hematologic adverse events were fever (24.5%), fatigue (20.8%), respiratory infection (18.9%) and dyspnea (15.1%). No grade 2-3 neurotoxicity was observed. Febrile neutropenia occurred in two (1.9%) patients; moreover, there were two deaths (3.8%) possibly related to treatment. In the intention-to-treat population, the objective response rate was 17% and 26.4% of pts achieved disease stabilization. No difference in response rates was observed in patients with squamous subtype (squamous vs others, 18.2% vs 16.1%, p=0.845). The median time-to-tumor progression was 2.5 months (95% CI 1.4-3.7), the median overall survival 10.6 months (95% CI 8.9-12.4) and the probability of 1-year survival 38.1%. Conclusions: The combination of bortezomib with GEM/CDDP in the dose and schedule used in this study does not seem to enhance the activity of the chemotherapy doublet. Clinical trial information: NCT01633645.