Bortezomib plus gemcitabine/carboplatin as first-line treatment of advanced non-small cell lung cancer: A phase II southwest oncology group study (S0339)

Angela M. Davies, Kari Chansky, Primo N Lara, Paul H. Gumerlock, John Crowley, Kathy S. Albain, Stanley J. Vogel, David R Gandara

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

Abstract

INTRODUCTION: Bortezomib is a small-molecule proteasome inhibitor with single-agent activity in patients with non-small cell lung carcinoma (NSCLC) and synergy with gemcitabine in preclinical studies. This phase II study of bortezomib in combination with gemcitabine/carboplatin was conducted in chemotherapy-naive advanced NSCLC patients to assess efficacy and safety. METHODS: Patients with selected stage IIIB/IV NSCLC, performance status 0-1, and no history of brain metastasis received up to six 21-day cycles of gemcitabine 1000 mg/m, days 1 and 8, carboplatin area under curve 5.0, day 1, and bortezomib 1.0 mg/m, days 1, 4, 8, and 11. RESULTS: One-hundred-fourteen patients (52% adenocarcinoma, 85% stage IV) received a median of 3.6 treatment cycles. Median follow-up was >3 years. Median overall survival was 11 months; 1-year and 2-year survival rates were 47% and 19%, respectively. Median progression-free survival was 5 months; 1-year progression-free survival rate was 7%. Response rate was 23%, and disease control rate (responses + stable disease) was 68%. The most common grade 3/4 toxicities were thrombocytopenia (63%) and neutropenia (52%). One patient experienced febrile neutropenia. Grade 3/4 neuropathy occurred in 4%, and a further 6% experienced grade 2 sensory neuropathy. CONCLUSIONS: Bortezomib plus gemcitabine/carboplatin resulted in a notable survival benefit in patients with advanced NSCLC, with the anticipated primary toxicity of myelosuppression. Further studies designed to investigate the role of bortezomib in advanced NSCLC are warranted.

Original languageEnglish (US)
Pages (from-to)87-92
Number of pages6
JournalJournal of Thoracic Oncology
Volume4
Issue number1
DOIs
StatePublished - Jan 2009

Keywords

  • Advanced NSCLC
  • Bortezomib
  • Carboplatin
  • Gemcitabine
  • Proteasome
  • Stage IV

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Medicine(all)

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