- 作者：Paul W. Sperduto ; MD ; MPP&lowast ; ; psperduto@mropa.com ; Meihua Wang ; PhD&dagger ; ; H. Ian Robins ; MD ; PhD&Dagger ; ; Michael C. Schell ; PhD§ ; ; Maria Werner-Wasik ; MD¡¬ ; Ritsuko Komaki ; MD¶ ; ; Luis Souhami ; MD# ; Mark K. Buyyounouski ; MD&lowast ; &lowast ; ; Deepak Khuntia ; MD&dagger ; &dagger ; ; William Demas ; MD&Dagger ; &Dagger ; ; Sunjay A. Shah ; MD§ ; § ; ; Lucien A. Nedzi ; MD¡¬¡¬ ; Gad Perry ; MD¶ ; ¶ ; ; John H. Suh ; MD## ; Minesh P. Mehta ; MD&lowast ; &lowast ; &lowast ;
- 刊名：International Journal of Radiation Oncology*Biology*Physics
- 出版年：2013
- 出版时间：1 April, 2013
- 年：2013
- 卷：85
- 期：5
- 页码：1312-1318
- 全文大小：274 K
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 and Materials
NSCLC patients with 1 to 3 brain metastases were randomized to receive WBRT (2.5 Gy ¡Á 15 to 37.5 Gy) and SRS alone, versus WBRT + SRS + TMZ (75 mg/m2/day ¡Á 21 days) or ETN (150 mg/day). ETN (150 mg/day) or TMZ (150-200 mg/m2/day ¡Á 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).
Conclusion
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.