title: Whole-brain irradiation with concomitant daily fixed-dose temozolomide for brain metastases treatment: a randomised phase II trial.
abstract: OBJECTIVE
  This randomised phase II study evaluated the use of Temozolomide (TMZ) concomitant with 30 Gray (Gy) of Whole-brain irradiation (WBI) for 2 weeks without adjuvant TMZ vs. WBI alone in patients with Brain metastases (BM) from solid tumours.
  
  
  METHODS
  Fifty-five patients were randomised into the following groups: 28 patients received WBI (30 Gy in 10 fractions over 2 weeks) concomitant with once-daily 200 mg TMZ on Mondays, Wednesdays, and Fridays, and 300 mg TMZ on Tuesdays and Thursdays (TMZ plus WBI arm). Twenty-seven patients received the same schedule of WBI alone (control arm).
  
  
  RESULTS
  The objective response (OR) was 78.6% for the TMZ plus WBI arm, (95% confidence interval [CI], 63.4-93.8%) and 48.1% (29.3-66.9%) for the control arm (p=0.019). Median Progression-free survival (PFS) of BM was 11.8 months (CI, 4.7-8.9 months) and 5.6 months (4.9-6.2 months) for the TMZ plus WBI and control arms, respectively, (Hazard ratio [HR], 0.24; CI, 0.09-0.65; p=0.005). Overall survival (OS) of 8.0 Months for the TMZ plus WBI arm and 8.1 months for the control arm, were not significantly different.
  
  
  CONCLUSIONS
  A daily fixed dose of TMZ during WBI without adjuvant TMZ was well tolerated and significantly improved local control of BM compared with WBI alone. These findings require confirmation in a phase III trial (ClinicalTrials.gov number, NCT01015534).
authors.affiliation: Department of Radiation Oncology, Instituto Nacional de Cancerología (INCan), México City, Mexico. cswgamboa@yahoo.com
authors.forename: Carlos
authors.initials: C
authors.lastname: Gamboa-Vignolle
authors.forename: Tabaré
authors.initials: T
authors.lastname: Ferrari-Carballo
authors.forename: Óscar
authors.initials: Ó
authors.lastname: Arrieta
authors.forename: Alejandro
authors.initials: A
authors.lastname: Mohar
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy* / Q000556:secondary*; D016009:Chi-Square Distribution; D016371:Cranial Irradiation / Q000379:methods*; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019583:Dose Fractionation, Radiation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011879:Radiotherapy Dosage; D015996:Survival Rate; D000077204:Temozolomide; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide