title: Phase II study of the proteasome inhibitor bortezomib (PS-341, Velcade) in chemotherapy-naïve patients with advanced stage non-small cell lung cancer (NSCLC).
abstract: The primary objective of this study was to determine the objective response rate of bortezomib as a first-line therapy in patients advanced stage NSCLC. Advanced/metastatic NSCLC patients with measurable disease, adequate organ function, ECOG performance status of 0-2, and no prior chemotherapy for metastatic disease were eligible. Patients received intravenously bolus bortezomib 1.3mg/m(2)/day on days 1, 4, 8 and 11 every 21 days for a maximum of 8 cycles, or until disease progression, or unacceptable toxicity. Tumor response was evaluated after every 2 cycles of therapy. This single-arm phase II study employed the Simon's two-stage design. The study was terminated in the first stage after 14 patients enrolled at 4 institutions. No objective response was observed. Three patients (21%) had stable disease and received 8, 6 and 4 cycles of treatment; the duration of stable disease was 11.5, 4.2 and 3.4 months, respectively. Median time to progression was 1.3 months (95% CI, 0.6-3.0 months); median overall survival (OS) was 9.9 months (95% CI, 2.2-27.0 months). Twelve patients received at least one dose of bortezomib. There were no grade 4 toxicities or treatment related deaths. Grade 3 toxicities included fatigue (N=1, 8%), deep vein thrombosis (N=1, 8%) and thrombocytopenia (N=1, 8%). Although well tolerated, bortezomib monotherapy is not active in this cohort of chemotherapy-naïve, metastatic NSCLC.
authors.affiliation: Department of Oncology, Montefiore Medical Center & the Albert Einstein College of Medicine, Bronx, NY, United States. tli@montefiore.org
authors.forename: Tianhong
authors.initials: T
authors.lastname: Li
authors.forename: Liawaty
authors.initials: L
authors.lastname: Ho
authors.forename: Bilal
authors.initials: B
authors.lastname: Piperdi
authors.forename: Tarek
authors.initials: T
authors.lastname: Elrafei
authors.forename: Fernando J
authors.initials: FJ
authors.lastname: Camacho
authors.forename: James R
authors.initials: JR
authors.lastname: Rigas
authors.forename: Roman
authors.initials: R
authors.lastname: Perez-Soler
authors.forename: Rasim
authors.initials: R
authors.lastname: Gucalp
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001897:Boronic Acids / Q000008:administration & dosage* / Q000009:adverse effects; D000069286:Bortezomib; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D018450:Disease Progression; D057239:Early Termination of Clinical Trials; D005221:Fatigue / Q000209:etiology; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011480:Protease Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011719:Pyrazines / Q000008:administration & dosage* / Q000009:adverse effects; D017211:Treatment Failure; D047368:Tumor Burden / Q000187:drug effects*; D020246:Venous Thrombosis / Q000209:etiology
chemical_list: D001897:Boronic Acids; D011480:Protease Inhibitors; D011719:Pyrazines; D000069286:Bortezomib