title: Pemetrexed, oxaliplatin and bevacizumab as first-line treatment in patients with stage IV non-small cell lung cancer.
abstract: BACKGROUND
  Oxaliplatin has less haematological toxicity than cisplatin and carboplatin. The combination of pemetrexed, oxaliplatin and bevacizumab appeared well tolerated and active as second- or third-line treatment in a previous phase II study. Its role as first-line therapy remains to define.
  
  
  METHODS
  From August 2008 to May 2011, consecutive chemo-naïve patients with stage IV non-squamous non-small cell lung cancer (NSCLC) received pemetrexed 500mg/m(2), oxaliplatin 100mg/m(2) and bevacizumab 7.5mg/kg every 3 weeks for 6 cycles, in the outpatient setting. Maintenance therapy including pemetrexed and bevacizumab was given to patients with non-progressive disease. The primary evaluation criterion was safety. Secondary evaluation criteria were response rate, progression-free survival (PFS) and overall survival (OS).
  
  
  RESULTS
  Thirty-eight patients (50% males, median age: 55 years, range 38-76) received a total of 199 cycles (median per patient: 6, range 2-6), plus 98 cycles of maintenance therapy. Twenty patients (52.6%) had a PS of 2, and 6 (15.8%) had brain metastases. The most frequent toxicities were hypertension (all grades: 42.1%) and peripheral neuropathy (grade 2-3: 21.1%). Haematological toxicities included grade 4 neutropenia, grade 3 anaemia and thrombopenia (5.3% each). Neither febrile neutropenia nor arterial thrombo-embolic event occurred. The objective response rate was 55.3% (95%CI: 39.5-71.1). The median PFS and OS were 6.2 (95%CI: 5.4-9.0) and 14.6 (95%CI: 9.8-19.5) months, respectively.
  
  
  CONCLUSIONS
  In this single centre experience, the combination of pemetrexed, oxaliplatin and bevacizumab was well tolerated and had promising activity as first-line therapy in unselected patients with stage IV non-squamous NSCLC.
authors.affiliation: Department of Medical Oncology, Cochin Teaching Hospital, AP-HP, Université Paris Descartes, Sorbonne Paris Cité, Paris, France. olivier.mir@cch.aphp.fr
authors.forename: Olivier
authors.initials: O
authors.lastname: Mir
authors.forename: Pascaline
authors.initials: P
authors.lastname: Boudou-Rouquette
authors.forename: Julie
authors.initials: J
authors.lastname: Giroux
authors.forename: Jeanne
authors.initials: J
authors.lastname: Chapron
authors.forename: Jérôme
authors.initials: J
authors.lastname: Alexandre
authors.forename: Laure
authors.initials: L
authors.lastname: Gibault
authors.forename: Stanislas
authors.initials: S
authors.lastname: Ropert
authors.forename: Romain
authors.initials: R
authors.lastname: Coriat
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Durand
authors.forename: Pierre-Régis
authors.initials: PR
authors.lastname: Burgel
authors.forename: Daniel
authors.initials: D
authors.lastname: Dusser
authors.forename: François
authors.initials: F
authors.lastname: Goldwasser
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D000068437:Pemetrexed; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D005971:Glutamates; D009944:Organoplatinum Compounds; D000068437:Pemetrexed; D000077150:Oxaliplatin; D000068258:Bevacizumab; D006147:Guanine