Phase II study of the proteasome inhibitor bortezomib (PS-341, Velcade®) in chemotherapy-naïve patients with advanced stage non-small cell lung cancer (NSCLC)

Tianhong Li, Liawaty Ho, Bilal Piperdi, Tarek Elrafei, Fernando J. Camacho, James R. Rigas, Roman Perez-Soler, Rasim A. Gucalp

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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 1.3 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.

Original languageEnglish (US)
Pages (from-to)89-93
Number of pages5
JournalLung Cancer
Volume68
Issue number1
DOIs
StatePublished - Apr 2010

Fingerprint

Proteasome Inhibitors
Non-Small Cell Lung Carcinoma
Drug Therapy
Therapeutics
Venous Thrombosis
Fatigue
Disease Progression
Bortezomib
Survival
Neoplasms

Keywords

  • Bortezomib
  • First-line therapy
  • Metastatic
  • Monotherapy
  • Non-small cell lung cancer
  • Phase II Study
  • Proteasome inhibitor

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

Cite this

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title = "Phase II study of the proteasome inhibitor bortezomib (PS-341, Velcade{\circledR}) in chemotherapy-na{\"i}ve 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 1.3 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-na{\"i}ve, metastatic NSCLC.",
keywords = "Bortezomib, First-line therapy, Metastatic, Monotherapy, Non-small cell lung cancer, Phase II Study, Proteasome inhibitor",
author = "Tianhong Li and Liawaty Ho and Bilal Piperdi and Tarek Elrafei and Camacho, {Fernando J.} and Rigas, {James R.} and Roman Perez-Soler and Gucalp, {Rasim A.}",
year = "2010",
month = "4",
doi = "10.1016/j.lungcan.2009.05.009",
language = "English (US)",
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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 A.

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

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U2 - 10.1016/j.lungcan.2009.05.009

DO - 10.1016/j.lungcan.2009.05.009

M3 - Article

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SP - 89

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JO - Lung Cancer

JF - Lung Cancer

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