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

Journal Article · Mon Apr 01 04:00:00 EDT 2013 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/J.IJROBP.2012.11.042· OSTI ID:22224423

Wang, Meihua ^[1]; Robins, H. Ian ^[2]; Schell, Michael C. ^[3]; Werner-Wasik, Maria ^[4]; Komaki, Ritsuko ^[5]; Souhami, Luis ^[6]; Buyyounouski, Mark K. ^[7]; Khuntia, Deepak ^[8]; Demas, William ^[9]; Shah, Sunjay A. ^[10]; Nedzi, Lucien A. ^[11]; Perry, Gad ^[12]; Suh, John H. ^[13]; Mehta, Minesh P. ^[14]

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1. RTOG Statistical Center, Philadelphia, Pennsylvania (United States)
2. University of Wisconsin Medical School Cancer Center, Madison, Wisconsin (United States)
3. Wilmot Cancer Center, University of Rochester, Rochester, New York (United States)
4. Thomas Jefferson University, Philadelphia, Pennsylvania (United States)
5. University of Texas MD Anderson Cancer Center, Houston, Texas (United States)
6. McGill University, Montreal, Quebec (Canada)
7. Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States)
8. University of Wisconsin Hospital, Madison, Wisconsin (United States)
9. Akron City Hospital, Akron, Ohio (United States)
10. Christiana Care Health Services, Inc, CCOP, Newark, Delaware (United States)
11. University of Texas Southwestern Medical School, Dallas, Texas (United States)
12. The Ottawa Hospital Cancer Centre, Ottawa, Ontario (Canada)
13. Cleveland Clinic Foundation, Cleveland, Ohio (United States)
14. Northwestern Memorial Hospital, Chicago, Illinois (United States)

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 × 15 to 37.5 Gy) and SRS alone, versus WBRT + SRS + TMZ (75 mg/m{sup 2}/day × 21 days) or ETN (150 mg/day). ETN (150 mg/day) or TMZ (150-200 mg/m{sup 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). 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.

• OSTI ID: 22224423
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Journal Name: International Journal of Radiation Oncology, Biology and Physics Journal Issue: 5 Vol. 85; ISSN IOBPD3; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
BLOOD-BRAIN BARRIER
BRAIN
DRUGS
LUNGS
METASTASES
NEOPLASMS
PATIENTS
RADIOTHERAPY
SURGERY
TOXICITY