title: Bortezomib plus gemcitabine/carboplatin as first-line treatment of advanced non-small cell lung cancer: a phase II Southwest Oncology Group Study (S0339).
abstract: BACKGROUND
  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.
authors.affiliation: Department of Hematology/Oncology, University of California, Davis Cancer Center, Sacramento, California, USA. adavies@osip.com
authors.forename: Angela M
authors.initials: AM
authors.lastname: Davies
authors.forename: Kari
authors.initials: K
authors.lastname: Chansky
authors.forename: Primo N
authors.initials: PN
authors.lastname: Lara
authors.forename: Paul H
authors.initials: PH
authors.lastname: Gumerlock
authors.forename: John
authors.initials: J
authors.lastname: Crowley
authors.forename: Kathy S
authors.initials: KS
authors.lastname: Albain
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: Vogel
authors.forename: David R
authors.initials: DR
authors.lastname: Gandara
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000556:secondary; D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000188:drug therapy / Q000556:secondary; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D016190:Carboplatin / Q000008:administration & dosage; D018287:Carcinoma, Large Cell / Q000188:drug therapy / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000556:secondary; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000556:secondary; D015331:Cohort Studies; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011719:Pyrazines / Q000008:administration & dosage; D015996:Survival Rate; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D001897:Boronic Acids; D011719:Pyrazines; D003841:Deoxycytidine; D000069286:Bortezomib; D016190:Carboplatin; D000093542:Gemcitabine