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

Lung Cancer. 2010 Apr;68(1):89-93. doi: 10.1016/j.lungcan.2009.05.009. Epub 2009 Jun 12.

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.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Boronic Acids / administration & dosage*
  • Boronic Acids / adverse effects
  • Bortezomib
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / physiopathology
  • Disease Progression
  • Early Termination of Clinical Trials
  • Fatigue / etiology
  • Female
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / physiopathology
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Protease Inhibitors / administration & dosage*
  • Protease Inhibitors / adverse effects
  • Pyrazines / administration & dosage*
  • Pyrazines / adverse effects
  • Treatment Failure
  • Tumor Burden / drug effects*
  • Venous Thrombosis / etiology

Substances

  • Boronic Acids
  • Protease Inhibitors
  • Pyrazines
  • Bortezomib