title: A phase II trial of vinorelbine and intensive temozolomide for patients with recurrent or progressive brain metastases.
abstract: OBJECTIVE
  To investigate the efficacy and safety of the combination of vinorelbine and intensive temozolomide for recurrent or progressive brain metastases from solid tumors.
  
  
  METHODS
  Patients > or =18 years of age and with Karnofsky performance scale (KPS) > or = 60, adequate organ function and progressive or recurrent brain metastases were eligible. This was a phase II trial with 28-day cycles using temozolomide (150 mg/m(2), days 1-7 and 15-21) and vinorelbine 25 or 30 mg/m(2 )on days one and eight. The primary endpoint was objective radiographic response.
  
  
  RESULTS
  Thirty-eight patients (15 men, 23 women) with a median age of 57 years (range, 39-75) and median KPS of 80 were enrolled. The primary tumor sites were lung (n = 20), breast (n = 11), colorectal (n = 2), kidney (n = 2), bladder (n = 1), endometrium (n = 1), head and neck (n = 1). Prior therapies included chemotherapy (97%), whole-brain radiation therapy (79%), brain metastasis resection (53%) and stereotatic radiosurgery (47%). Objective radiographic response rate was 5% (one complete response and one minor response); five patients had stable disease, 29 progressive disease and two patients were not evaluable. Twenty-nine patients (76%) have died and the median follow-up of survivors was six months. Median progression-free and overall survivals were 1.9 and 5 months, respectively. Grade 3/4 toxicities were mainly hematological and two patients discontinued the study due to myelosuppression.
  
  
  CONCLUSIONS
  In this heavily pretreated population of patients with brain metastases, adding vinorelbine and increasing the intensity of temozolomide do not improve response rates compared to previous studies with single-agent temozolomide at standard doses.
authors.affiliation: Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY, 10021, USA.
authors.forename: Fabio M
authors.initials: FM
authors.lastname: Iwamoto
authors.forename: Antonio M
authors.initials: AM
authors.lastname: Omuro
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Raizer
authors.forename: Craig P
authors.initials: CP
authors.lastname: Nolan
authors.forename: Adília
authors.initials: A
authors.lastname: Hormigo
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Lassman
authors.forename: Igor T
authors.initials: IT
authors.lastname: Gavrilovic
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Abrey
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary*; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality; D016019:Survival Analysis; D000077204:Temozolomide; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000077235:Vinorelbine
chemical_list: D014747:Vinblastine; D003606:Dacarbazine; D000077235:Vinorelbine; D000077204:Temozolomide