title: A randomized phase II study of bortezomib and pemetrexed, in combination or alone, in patients with previously treated advanced non-small-cell lung cancer.
abstract: BACKGROUND
  This is a phase II randomized study to evaluate the efficacy and safety of bortezomib and pemetrexed alone or in combination, in patients with previously treated advanced non-small-cell lung cancer (NSCLC). The primary end point was assessment of response rate.
  
  
  METHODS
  A total of 155 patients were randomized (1:1:1) to pemetrexed (500mg/m(2)) on day 1 plus bortezomib (1.6mg/m(2)) on days 1 and 8 (Arm A) or pemetrexed (500mg/m(2)) on day 1 (Arm B) or bortezomib (1.6mg/m(2)) on days 1 and 8 (Arm C) of a 21 day cycle. Response rate was assessed by investigators using Response Evaluation Criteria In Solid Tumors (RECIST) criteria and toxicity assessed by the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) grading system.
  
  
  RESULTS
  Response rate was 7% in Arm A, 4% in Arm B, and 0% in Arm C; disease control rates were 73%, 62%, and 43%, respectively. Median overall survival was 8.6 months in Arm A, 12.7 months in Arm B, and 7.8 months in Arm C; time to progression was 4.0 months, 2.9 months, and 1.4 months, respectively. Most common reported adverse events >/=grade 3 were neutropenia (19%), thrombocytopenia (15%), and dyspnea (13%) in Arm A, neutropenia (10%) in Arm B, and dyspnea (13%) and fatigue (10%) in Arm C.
  
  
  CONCLUSIONS
  In previously treated NSCLC the addition of bortezomib to pemetrexed was well tolerated but offered no statistically significant response or survival advantage versus pemetrexed alone, while bortezomib alone showed no clinically significant activity.
authors.affiliation: University of Torino, Department of Clinical & Biological Sciences, Thoracic Oncology Unit, S. Luigi Hospital, Regione Gonzole 10, Orbassano (Torino) 10043, Italy. giorgio.scagliotti@unito.it
authors.forename: Giorgio V
authors.initials: GV
authors.lastname: Scagliotti
authors.forename: Paul
authors.initials: P
authors.lastname: Germonpré
authors.forename: Leon
authors.initials: L
authors.lastname: Bosquée
authors.forename: Johan
authors.initials: J
authors.lastname: Vansteenkiste
authors.forename: R
authors.initials: R
authors.lastname: Gervais
authors.forename: David
authors.initials: D
authors.lastname: Planchard
authors.forename: Martin
authors.initials: M
authors.lastname: Reck
authors.forename: Filippo
authors.initials: F
authors.lastname: De Marinis
authors.forename: Jin Soo
authors.initials: JS
authors.lastname: Lee
authors.forename: Keunchil
authors.initials: K
authors.lastname: Park
authors.forename: Bonne
authors.initials: B
authors.lastname: Biesma
authors.forename: Steven
authors.initials: S
authors.lastname: Gans
authors.forename: R
authors.initials: R
authors.lastname: Ramlau
authors.forename: Aleusandra
authors.initials: A
authors.lastname: Szczesna
authors.forename: A
authors.initials: A
authors.lastname: Makhson
authors.forename: G
authors.initials: G
authors.lastname: Manikhas
authors.forename: Bruno
authors.initials: B
authors.lastname: Morgan
authors.forename: Y
authors.initials: Y
authors.lastname: Zhu
authors.forename: Kai C
authors.initials: KC
authors.lastname: Chan
authors.forename: Joachim
authors.initials: J
authors.lastname: von Pawel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001897:Boronic Acids / Q000008:administration & dosage* / Q000009:adverse effects; D000069286:Bortezomib; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D018450:Disease Progression; D004359:Drug Therapy, Combination; D004417:Dyspnea / Q000209:etiology; D005260:Female; D005971:Glutamates / Q000008:administration & dosage* / Q000009:adverse effects; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009503:Neutropenia / Q000209:etiology; D000068437:Pemetrexed; D011719:Pyrazines / Q000008:administration & dosage* / Q000009:adverse effects; D016019:Survival Analysis; D013921:Thrombocytopenia / Q000209:etiology
chemical_list: D001897:Boronic Acids; D005971:Glutamates; D011719:Pyrazines; D000068437:Pemetrexed; D006147:Guanine; D000069286:Bortezomib