title: An open-label, multicenter, randomized, phase II study of pazopanib in combination with pemetrexed in first-line treatment of patients with advanced-stage non-small-cell lung cancer.
abstract: BACKGROUND
  This randomized open-label phase II study evaluated the efficacy, safety, and tolerability of pazopanib in combination with pemetrexed compared with the standard cisplatin/pemetrexed doublet in patients with previously untreated, advanced, nonsquamous non-small-cell lung cancer.
  
  
  METHODS
  Patients were randomized (2:1 ratio) to receive pemetrexed 500 mg/m(2) intravenously once every 3 weeks plus either oral pazopanib 800 mg daily or cisplatin 75 mg/m(2) intravenously once every 3 weeks up to six cycles. All patients received folic acid, vitamin B12, and steroid prophylaxis. The primary endpoint was progression-free survival (PFS).
  
  
  RESULTS
  The study was terminated after 106 of 150 patients were randomized due to a higher incidence of adverse events leading to withdrawal from the study and severe and fatal adverse events in the pazopanib/pemetrexed arm than in the cisplatin/pemetrexed arm. At the time enrolment was discontinued, there were three fatal adverse events in the pazopanib/pemetrexed arm, including ileus, tumor embolism, and bronchopneumonia/sepsis. Treatment with pazopanib/pemetrexed was discontinued resulting in more PFS data censored for patients in the pazopanib/pemetrexed arm than those in the cisplatin/pemetrexed arm. There was no statistically significant difference between the pazopanib/pemetrexed and cisplatin/pemetrexed arms for PFS (median PFS, 25.0 versus 22.9 weeks, respectively; hazard ratio = 0.75; 95% confidence interval, 0.43%-1.28%; p = 0.26) or objective response rate (23% versus 34%, respectively; 95% confidence interval, -30.6% to 7.2%; p = 0.21).
  
  
  CONCLUSIONS
  The combination of pazopanib/pemetrexed in first-line treatment of non-small-cell lung cancer showed some antitumor activity but had unacceptable levels of toxicity.
authors.affiliation: *Department of Clinical and Biological Sciences, University of Turin, Orbassano, Torino, Italy; †Department of Oncology, Vall d'Hebron University Hospital, Barcelona, Spain; ‡Department of Cancer Medicine, Institut Gustave Roussy, Villejuif, France; §Asklepios Clinic, Asklepios Fachkliniken München-Gauting, Gauting, Germany; ‖Department of Oncology, Herlev Hospital, Onkologisk afdeling, Herlev, Denmark; ¶Department of Thoracic Oncology, Hospital Grosshansdorf, Grosshansdorf, Germany; #Department of Respiratory Medicine, Centre Hospitalier Universitaire de Liege, Liege, Belgium; **Department of Respiratory Medicine, Hopital Saint-Antoine, Paris Cedex, France; ††Department of Medical Oncology, Hospital de Mataro, Mataro, Spain; and ‡‡Oncology Research and Development, GlaxoSmithKline, Research Triangle Park, North Carolina; Collegeville, Philadelphia, Pennsylvania; and Uxbridge, United Kingdom.
authors.forename: Giorgio V
authors.initials: GV
authors.lastname: Scagliotti
authors.forename: Enriqueta
authors.initials: E
authors.lastname: Felip
authors.forename: Benjamin
authors.initials: B
authors.lastname: Besse
authors.forename: Joachim
authors.initials: J
authors.lastname: von Pawel
authors.forename: Anders
authors.initials: A
authors.lastname: Mellemgaard
authors.forename: Martin
authors.initials: M
authors.lastname: Reck
authors.forename: Lionel
authors.initials: L
authors.lastname: Bosquee
authors.forename: Christos
authors.initials: C
authors.lastname: Chouaid
authors.forename: Pilar
authors.initials: P
authors.lastname: Lianes-Barragán
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Paul
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Ruiz-Soto
authors.forename: Entisar
authors.initials: E
authors.lastname: Sigal
authors.forename: Lone H
authors.initials: LH
authors.lastname: Ottesen
authors.forename: Thierry
authors.initials: T
authors.lastname: Lechevalier
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018287:Carcinoma, Large Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D007191:Indazoles; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D000068437:Pemetrexed; D011379:Prognosis; D011743:Pyrimidines / Q000008:administration & dosage; D013449:Sulfonamides / Q000008:administration & dosage; D015996:Survival Rate
chemical_list: D005971:Glutamates; D007191:Indazoles; D011743:Pyrimidines; D013449:Sulfonamides; D000068437:Pemetrexed; D006147:Guanine; C516667:pazopanib; D002945:Cisplatin