A Phase I Study of the Combination of Sorafenib With Temozolomide and Radiation Therapy for the Treatment of Primary and Recurrent High-Grade Gliomas

Journal Article · Fri Feb 01 04:00:00 EST 2013 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/J.IJROBP.2012.04.017· OSTI ID:22149753

Kamrava, Mitchell ^[1]; Sheng, Zhi ^[2]; Werner-Wasik, Maria; Dougherty, Erin; Marinucchi, Michelle ^[3]; Lawrence, Yaacov R. ^[3]; Hegarty, Sarah; Hyslop, Terry ^[4]; Andrews, David W.; Glass, Jon ^[5]; Friedman, David P. ^[6]; Green, Michael R. ^[2]; Camphausen, Kevin ^[1]; Dicker, Adam P. ^[3]

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1. Radiation Oncology Branch, National Cancer Institute, Bethesda, Maryland (United States)
2. Howard Hughes Medical Institute, Programs in Gene Function and Expression and Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts (United States)
3. Department of Radiation Oncology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States)
4. Department of Biostatistics, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States)
5. Department of Neurosurgery, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States)
6. Department of Radiology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States)

Purpose: Despite recent advances in the management of high-grade and recurrent gliomas, survival remains poor. Antiangiogenic therapy has been shown to be efficacious in the treatment of high-grade gliomas both in preclinical models and in clinical trials. We sought to determine the safety and maximum tolerated dose of sorafenib when combined with both radiation and temozolomide in the primary setting or radiation alone in the recurrent setting. Methods and Materials: This was a preclinical study and an open-label phase I dose escalation trial. Multiple glioma cell lines were analyzed for viability after treatment with radiation, temozolomide, or sorafenib or combinations of them. For patients with primary disease, sorafenib was given concurrently with temozolomide (75 mg/m{sup 2}) and 60 Gy radiation, for 30 days after completion of radiation. For patients with recurrent disease, sorafenib was combined with a hypofractionated course of radiation (35 Gy in 10 fractions). Results: Cell viability was significantly reduced with the combination of radiation, temozolomide, and sorafenib or radiation and sorafenib. Eighteen patients (11 in the primary cohort, 7 in the recurrent cohort) were enrolled onto this trial approved by the institutional review board. All patients completed the planned course of radiation therapy. The most common toxicities were hematologic, fatigue, and rash. There were 18 grade 3 or higher toxicities. The median overall survival was 18 months for the entire population. Conclusions: Sorafenib can be safely combined with radiation and temozolomide in patients with high-grade glioma and with radiation alone in patients with recurrent glioma. The recommended phase II dose of sorafenib is 200 mg twice daily when combined with temozolomide and radiation and 400 mg with radiation alone. To our knowledge, this is the first publication of concurrent sorafenib with radiation monotherapy or combined with radiation and temozolomide.

• OSTI ID: 22149753
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Journal Name: International Journal of Radiation Oncology, Biology and Physics Journal Issue: 2 Vol. 85; ISSN IOBPD3; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
CLINICAL TRIALS
FATIGUE
GLIOMAS
PATIENTS
RADIATION DOSES
RADIOTHERAPY
TOXICITY
VIABILITY