TY - JOUR
T1 - Phase II study of the proteasome inhibitor bortezomib (PS-341, Velcade®) in chemotherapy-naïve patients with advanced stage non-small cell lung cancer (NSCLC)
AU - Li, Tianhong
AU - Ho, Liawaty
AU - Piperdi, Bilal
AU - Elrafei, Tarek
AU - Camacho, Fernando J.
AU - Rigas, James R.
AU - Perez-Soler, Roman
AU - Gucalp, Rasim
N1 - Funding Information:
Grant : This study was supported by funding from Millennium: The Takeda Oncology Company.
PY - 2010/4
Y1 - 2010/4
N2 - 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 1.3 mg/m2/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.
AB - 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 1.3 mg/m2/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.
KW - Bortezomib
KW - First-line therapy
KW - Metastatic
KW - Monotherapy
KW - Non-small cell lung cancer
KW - Phase II Study
KW - Proteasome inhibitor
UR - http://www.scopus.com/inward/record.url?scp=77649180963&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77649180963&partnerID=8YFLogxK
U2 - 10.1016/j.lungcan.2009.05.009
DO - 10.1016/j.lungcan.2009.05.009
M3 - Article
C2 - 19524318
AN - SCOPUS:77649180963
SN - 0169-5002
VL - 68
SP - 89
EP - 93
JO - Lung Cancer
JF - Lung Cancer
IS - 1
ER -