title: Pemetrexed and cisplatin as first-line chemotherapy for advanced non-small-cell lung cancer (NSCLC) with asymptomatic inoperable brain metastases: a multicenter phase II trial (GFPC 07-01).
abstract: BACKGROUND
  Brain metastases (BM) occur in up to 40% of non-small-cell lung cancer (NSCLC) patients. This trial assessed the safety and efficacy of pemetrexed-cisplatin in this population.
  
  
  METHODS
  Chemonaive NSCLC patients with BM ineligible for (radio)surgery, performance status (PS) of 0 to 2, were eligible for up to six cycles of cisplatin 75 mg/m(2) and pemetrexed 500 mg/m(2) every 3 weeks. Whole -brain radiotherapy was given in case of disease progression or at chemotherapy completion. Primary end point was objective response rate (RR) on BM. Secondary end points included extracerebral and overall RR, safety profile and survival.
  
  
  RESULTS
  Forty-three patients were enrolled. Initial characteristics were mean age 60.4 years; males 29; PS: 0 in 37.2%, 1 in 60.5% and 2 in 22.3% of patients; adenocarcinoma in 36 patients, large cell in 4 patients (nonsquamous, 93%) and squamous carcinoma in 3 patients. Functional classification of neurological status was stage I/II 86.0%, III 2.3% and IV 11.6%. Grade 3-4 hematological toxic effects were neutropenia, 11 patients (febrile neutropenia, 1 patient), and anemia, 6 patients. Non-hematological toxic effects were grade 2 urinary infection, one patient; grade 3 pneumonia, two patients; and grade 3 hypoacousia, one patient. Cerebral, extracerebral and overall RR by intent to treat analysis were 41.9%, 34.9% and 34.9%, respectively. Median survival time and time to progression were 7.4 and 4.0 months, respectively.
  
  
  CONCLUSIONS
  Pemetrexed-cisplatin is an effective and well-tolerated regimen as first-line therapy for NSCLC patients with BM who always suffer a poor prognosis.
authors.affiliation: Multidisciplinary Oncology and Therapeutic Innovations Department & Centre Investigation Clinique, University of Méditerranée-Assistance Publique Hôpitaux de Marseille, Marseille. Electronic address: fabrice.barlesi@ap-hm.fr.
authors.forename: F
authors.initials: F
authors.lastname: Barlesi
authors.affiliation: Department of Oncology, François Baclesse Center, Caen.
authors.forename: R
authors.initials: R
authors.lastname: Gervais
authors.affiliation: Department of Pneumology, Rennes University Hospital, Rennes.
authors.forename: H
authors.initials: H
authors.lastname: Lena
authors.affiliation: Department of Pneumology, Thorax and Vessel Center Academic Hospital, Angers.
authors.forename: J
authors.initials: J
authors.lastname: Hureaux
authors.affiliation: Department of Pneumology, Hopital d'Instruction des Armées Sainte-Anne, Toulon.
authors.forename: H
authors.initials: H
authors.lastname: Berard
authors.affiliation: Department of Pulmonary and Respiratory Intensive Care, Rouen University Hospital.
authors.forename: D
authors.initials: D
authors.lastname: Paillotin
authors.affiliation: Department of Pneumology, Rouen University Hospital, Charles Nicolle Hospital, Rouen.
authors.forename: S
authors.initials: S
authors.lastname: Bota
authors.affiliation: Department of Pneumology, Créteil Intercommunal Hospital Center, Créteil.
authors.forename: I
authors.initials: I
authors.lastname: Monnet
authors.affiliation: Department of Pneumology, Institute of Cancerology and Hematology, Centre Hospitalier Regional Universitaire, Morvan, Brest, France.
authors.forename: A
authors.initials: A
authors.lastname: Chajara
authors.affiliation: Department of Pneumology, Institute of Cancerology and Hematology, Centre Hospitalier Regional Universitaire, Morvan, Brest, France.
authors.forename: G
authors.initials: G
authors.lastname: Robinet
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000556:secondary*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; 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* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D000068437:Pemetrexed; D015996:Survival Rate
chemical_list: D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine; D002945:Cisplatin