title: A phase 3 trial of whole brain radiation therapy and stereotactic radiosurgery alone versus WBRT and SRS with temozolomide or erlotinib for non-small cell lung cancer and 1 to 3 brain metastases: Radiation Therapy Oncology Group 0320.
abstract: BACKGROUND
  A phase 3 Radiation Therapy Oncology Group (RTOG) study subset analysis demonstrated improved overall survival (OS) with the addition of stereotactic radiosurgery (SRS) to whole brain radiation therapy (WBRT) in non-small cell lung cancer (NSCLC) patients with 1 to 3 brain metastases. Because temozolomide (TMZ) and erlotinib (ETN) cross the blood-brain barrier and have documented activity in NSCLC, a phase 3 study was designed to test whether these drugs would improve the OS associated with WBRT + SRS.
  
  
  METHODS
  NSCLC patients with 1 to 3 brain metastases were randomized to receive WBRT (2.5 Gy × 15 to 37.5 Gy) and SRS alone, versus WBRT + SRS + TMZ (75 mg/m(2)/day × 21 days) or ETN (150 mg/day). ETN (150 mg/day) or TMZ (150-200 mg/m(2)/day × 5 days/month) could be continued for as long as 6 months after WBRT + SRS. The primary endpoint was OS.
  
  
  RESULTS
  After 126 patients were enrolled, the study closed because of accrual limitations. The median survival times (MST) for WBRT + SRS, WBRT + SRS + TMZ, and WBRT + SRS + ETN were qualitatively different (13.4, 6.3, and 6.1 months, respectively), although the differences were not statistically significant. Time to central nervous system progression and performance status at 6 months were better in the WBRT + SRS arm. Grade 3 to 5 toxicity was 11%, 41%, and 49% in arms 1, 2, and 3, respectively (P<.001).
  
  
  CONCLUSIONS
  The addition of TMZ or ETN to WBRT + SRS in NSCLC patients with 1 to 3 brain metastases did not improve survival and possibly had a deleterious effect. Because the analysis is underpowered, these data suggest but do not prove that increased toxicity was the cause of inferior survival in the drug arms.
authors: Metro MN CCOP, Minneapolis, Minnesota, USA. psperduto@mropa.com
authors: Paul W
authors: PW
authors: Sperduto
authors: Meihua
authors: M
authors: Wang
authors: H Ian
authors: HI
authors: Robins
authors: Michael C
authors: MC
authors: Schell
authors: Maria
authors: M
authors: Werner-Wasik
authors: Ritsuko
authors: R
authors: Komaki
authors: Luis
authors: L
authors: Souhami
authors: Mark K
authors: MK
authors: Buyyounouski
authors: Deepak
authors: D
authors: Khuntia
authors: William
authors: W
authors: Demas
authors: Sunjay A
authors: SA
authors: Shah
authors: Lucien A
authors: LA
authors: Nedzi
authors: Gad
authors: G
authors: Perry
authors: John H
authors: JH
authors: Suh
authors: Minesh P
authors: MP
authors: Mehta
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D003131:Combined Modality Therapy / Q000379:methods; D016371:Cranial Irradiation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000069347:Erlotinib Hydrochloride; D006801:Humans; D008175:Lung Neoplasms; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011799:Quinazolines / Q000627:therapeutic use*; D016634:Radiosurgery / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D011879:Radiotherapy Dosage; D000077204:Temozolomide
chemical_list: D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D003606:Dacarbazine; D000069347:Erlotinib Hydrochloride; D000077204:Temozolomide
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