A Phase III Study of Conventional Radiation Therapy Plus Thalidomide Versus Conventional Radiation Therapy for Multiple Brain Metastases (RTOG 0118)

Knisely, Jonathan P.S.; Berkey, Brian; Chakravarti, Arnab; Yung, Al W.K.; Curran, Walter J.; Robins, H. Ian; Movsas, Benjamin; Brachman, David G.; Henderson, Randall H.; Mehta, Minesh P.

doi:10.1016/j.ijrobp.2007.09.016

« Previous Next »International Journal of Radiation Oncology * Biology * Physics
Volume 71, Issue 1 , Pages 79-86, 1 May 2008

A Phase III Study of Conventional Radiation Therapy Plus Thalidomide Versus Conventional Radiation Therapy for Multiple Brain Metastases (RTOG 0118)

Jonathan P.S. Knisely, M.D., F.R.C.P.C.
- Department of Therapeutic Radiology, Yale University School of Medicine and Yale Cancer Center, New Haven, CT
- Reprint requests to: Jonathan P. S. Knisely, M.D., F.R.C.P.C., Yale University School of Medicine and Yale Cancer Center, 333 Cedar Street, 133 HRT, P.O. Box 208040, New Haven, CT 06520-8040. Tel: (203) 785-2960; Fax: (203) 785-4622
Brian Berkey, M.S.
- Radiation Therapy Oncology Group, Philadelphia, PA
Arnab Chakravarti, M.D.
- Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA
Al W.K. Yung, M.D.
- Department of Neuro-Oncology and Brain Tumor Center, The University of Texas M.D. Anderson Cancer Center, Houston, TX
Walter J. Curran Jr., M.D.
- Department of Radiation Oncology, Emory University, Atlanta, GA
H. Ian Robins, M.D., Ph.D.
- Department of Human Oncology, University of Wisconsin Medical School, Madison, WI
- Department of Medicine, University of Wisconsin Medical School, Madison, WI
Benjamin Movsas, M.D.
- Department of Radiation Oncology, Henry Ford Health System, Detroit, MI
David G. Brachman, M.D.
- Department of Radiation Oncology, AZ Oncology Services and St. Joseph's Hospital, Phoenix, AZ
Randall H. Henderson, M.D., M.B.A.
- University of Florida Proton Therapy Institute, Jacksonville, FL
Minesh P. Mehta, M.D.
- Department of Medicine, University of Wisconsin Medical School, Madison, WI

Received 18 June 2007; received in revised form 23 August 2007; accepted 24 September 2007. published online 03 January 2008.

Purpose

To compare whole-brain radiation therapy (WBRT) with WBRT combined with thalidomide for patients with brain metastases not amenable to resection or radiosurgery.

Patients and Methods

Patients with Zubrod performance status 0–1, MRI-documented multiple (>3), large (>4 cm), or midbrain brain metastases arising from a histopathologically confirmed extracranial primary tumor, and an anticipated survival of >8 weeks were randomized to receive WBRT to a dose of 37.5 Gy in 15 fractions with or without thalidomide during and after WBRT. Prerandomization stratification used Radiation Therapy Oncology Group (RTOG) Recursive Partitioning Analysis (RPA) Class and whether post-WBRT chemotherapy was planned. Endpoints included overall survival, progression-free survival, time to neurocognitive progression, the cause of death, toxicities, and quality of life. A protocol-planned interim analysis documented that the trial had an extremely low probability of ever showing a significant difference favoring the thalidomide arm given the results at the time of the analysis, and it was therefore closed on the basis of predefined statistical guidelines.

Results

Enrolled in the study were 332 patients. Of 183 accrued patients, 93 were randomized to receive WBRT alone and 90 to WBRT and thalidomide. Median survival was 3.9 months for both arms. No novel toxicities were seen, but thalidomide was not well tolerated in this population. Forty-eight percent of patients discontinued thalidomide because of side effects.

Conclusion

Thalidomide provided no survival benefit for patients with multiple, large, or midbrain metastases when combined with WBRT; nearly half the patients discontinued thalidomide due to side effects.

Brain metastases, Whole-brain radiotherapy, thalidomide, Phase III trial, antiangiogenesis