title: Phase II randomized study of whole-brain radiation therapy with or without concurrent temozolomide for brain metastases from breast cancer.
abstract: BACKGROUND
  To improve the therapeutic index of whole-brain radiation therapy (WBRT) in the treatment of brain metastases (BM) from breast cancer, we investigated the efficacy and safety of WBRT combined with temozolomide (TMZ) in this population.
  
  
  METHODS
  This phase II multicenter prospective randomized study included patients with newly diagnosed intraparenchymal BMs from breast cancer, unsuitable for surgery or radiosurgery. All patients received conformal WBRT (3 Gy × 10-30 Gy), with or without concomitant TMZ administered at a dosage of 75 mg/m(2)/day during the irradiation period. The primary end point was objective response rate (ORR) 6 weeks after the end of treatment, defined as a partial or complete response on systematic brain MRI (modified WHO criteria). Secondary end points were progression-free survival (PFS) and overall survival (OS), neurologic symptoms, and tolerability.
  
  
  RESULTS
  Between February 2008 and November 2010, 100 patients were enrolled in the study (50 in the WBRT + TMZ arm, 50 in the WBRT arm). Median age was 55 years (29-79). Median follow-up was 9.4 months [1.0-68.1]. ORRs at 6 weeks were 36% in the WBRT arm and 30% in the WBRT + TMZ arm (NS). In the WBRT arm, median PFS was 7.4 months and median OS was 11.1 months. In the WBRT + TMZ arm, median PFS was 6.9 months and median OS was 9.4 months. Treatment was well tolerated in this arm: the most common ≥grade 2 acute toxicity was reversible lymphopenia.
  
  
  CONCLUSIONS
  WBRT combined with TMZ did not significantly improve local control and survival in patients with BMs from breast cancer. CLINICALTRIALS.GOV: NCT00875355.
authors.affiliation: Department of Radiation Oncology.
authors.forename: K I
authors.initials: KI
authors.lastname: Cao
authors.affiliation: Department of Statistics.
authors.forename: N
authors.initials: N
authors.lastname: Lebas
authors.affiliation: Department of Radiology, Institut Curie, Paris.
authors.forename: S
authors.initials: S
authors.lastname: Gerber
authors.affiliation: Department of Radiation Oncology, Centre François Baclesse, Caen.
authors.forename: C
authors.initials: C
authors.lastname: Levy
authors.affiliation: Department of Radiation Oncology.
authors.forename: R
authors.initials: R
authors.lastname: Le Scodan
authors.affiliation: Department of Radiation Oncology, Institut Gustave Roussy, Villejuif.
authors.forename: C
authors.initials: C
authors.lastname: Bourgier
authors.affiliation: Department of Medical Oncology, Institut Curie, Paris, France.
authors.forename: J-Y
authors.initials: JY
authors.lastname: Pierga
authors.affiliation: Department of Statistics.
authors.forename: A
authors.initials: A
authors.lastname: Gobillion
authors.affiliation: Department of Statistics.
authors.forename: A
authors.initials: A
authors.lastname: Savignoni
authors.affiliation: Department of Radiation Oncology. Electronic address: youlia.kirova@curie.fr.
authors.forename: Y M
authors.initials: YM
authors.lastname: Kirova
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000532:radiotherapy* / Q000556:secondary; D001943:Breast Neoplasms / Q000473:pathology*; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008875:Middle Aged; D011446:Prospective Studies; D000077204:Temozolomide
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide
keywords: brain metastases; metastatic breast cancer; temozolomide; whole-brain radiation therapy