Abstract
BACKGROUND AND AIMS: Nonsmall cell lung cancer accounts for over 85% of lung cancer incidences worldwide, and often has a poor prognosis. Proteasome inhibitors, such as bortezomib, have previously demonstrated evidence in preclinical and clinical models in the treatment of NSCLC both alone and as part of chemotherapeutic regimens. METHODS: Five databases were searched from inception to February 2023 to identify published clinical trial data and ongoing clinical trials on the use of proteasome inhibitors in treatment of NSCLC with a comprehensive search strategy. RESULTS: This review examines the clinical evidence from 21 completed and published phase I and II trials studying the use of bortezomib monotherapy and combination therapy in the treatment of NSCLC. Bortezomib/docetaxel combination resulted in longer median time-to-progression (TTP), median duration of response, median duration of disease control and median progression-free survival (PFS) than bortezomib monotherapy, with concurrent administration having greater 6-month PFS and median overall survival (OS) than sequential administration. Bortezomib/vorinostat with chemotherapy was well tolerated and effective. Bortezomib/gemcitabine/carboplatin, bortezomib/bevacizumab/carboplatin and bortezomib/paclitaxel/carboplatin combinations showed promising results and were of further investigational value. CONCLUSION: Bortezomib showed some clinical promise in combination therapy but not monotherapy. It also demonstrated a manageable side effect profile. Combination regimens are of further investigation value in Phase II trials.