Phase II Pilot Study of Bevacizumab in Combination with Temozolomide and Regional Radiation Therapy for Up-Front Treatment of Patients With Newly Diagnosed Glioblastoma Multiforme: Interim Analysis of Safety and Tolerability

Lai, Albert; Filka, Emese; McGibbon, Bruce; Nghiemphu, Phioanh Leia; Graham, Carrie; Yong, William H.; Mischel, Paul; Liau, Linda M.; Bergsneider, Marvin; Pope, Whitney; Selch, Michael; Cloughesy, Tim

doi:10.1016/j.ijrobp.2007.11.068

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Volume 71, Issue 5 , Pages 1372-1380, 1 August 2008

Phase II Pilot Study of Bevacizumab in Combination with Temozolomide and Regional Radiation Therapy for Up-Front Treatment of Patients With Newly Diagnosed Glioblastoma Multiforme: Interim Analysis of Safety and Tolerability

Albert Lai, M.D., Ph.D.
- Department of Neurology, David Geffen School of Medicine at University of California–Los Angeles, Los Angeles, CA
- Reprint requests to: Albert Lai, M.D., Ph.D., UCLA Neuro-Oncology Program, Department of Neurology, David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Suite 1-230 RNRC, Los Angeles, CA 90095. Tel: (310) 825-5321; Fax: (310) 825-0644
Emese Filka
- Department of Neurology, David Geffen School of Medicine at University of California–Los Angeles, Los Angeles, CA
Bruce McGibbon, M.D.
- Department of Radiation Oncology, David Geffen School of Medicine at University of California–Los Angeles, Los Angeles, CA
Phioanh Leia Nghiemphu, M.D.
- Department of Neurology, David Geffen School of Medicine at University of California–Los Angeles, Los Angeles, CA
Carrie Graham
- Department of Neurology, David Geffen School of Medicine at University of California–Los Angeles, Los Angeles, CA
William H. Yong, M.D.
- Department of Pathology, David Geffen School of Medicine at University of California–Los Angeles, Los Angeles, CA
Paul Mischel, M.D.
- Department of Pathology, David Geffen School of Medicine at University of California–Los Angeles, Los Angeles, CA
Linda M. Liau, M.D., Ph.D.
- Department of Neurosurgery, David Geffen School of Medicine at University of California–Los Angeles, Los Angeles, CA
Marvin Bergsneider, M.D.
- Department of Neurosurgery, David Geffen School of Medicine at University of California–Los Angeles, Los Angeles, CA
Whitney Pope, M.D., Ph.D.
- Department of Radiology, David Geffen School of Medicine at University of California–Los Angeles, Los Angeles, CA
Michael Selch, M.D.
- Department of Radiation Oncology, David Geffen School of Medicine at University of California–Los Angeles, Los Angeles, CA
Tim Cloughesy, M.D.
- Department of Neurology, David Geffen School of Medicine at University of California–Los Angeles, Los Angeles, CA

Received 4 October 2007; received in revised form 29 November 2007; accepted 30 November 2007. published online 20 March 2008.

Purpose

To assess interim safety and tolerability of a 10-patient, Phase II pilot study using bevacizumab (BV) in combination with temozolomide (TMZ) and regional radiation therapy (RT) in the up-front treatment of patients with newly diagnosed glioblastoma.

Methods and Materials

All patients received standard external beam regional RT of 60.0 Gy in 30 fractions started within 3 to 5 weeks after surgery. Concurrently TMZ was given daily at 75 mg/m² for 42 days during RT, and BV was given every 2 weeks at 10 mg/kg starting with the first day of RT/TMZ. After a 2-week interval upon completion of RT, the post-RT phase commenced with resumption of TMZ at 150 to 200 mg/m² for 5 days every 4 weeks and continuation of BV every 2 weeks.

Results

For these 10 patients, toxicities were compiled until study discontinuation or up to ∼40 weeks from initial study treatment for those remaining on-study. In terms of serious immediate or delayed neurotoxicity, 1 patient developed presumed radiation-induced optic neuropathy. Among the toxicities that could be potentially treatment related, relatively high incidences of fatigue, myelotoxicity, wound breakdown, and deep venous thrombosis/pulmonary embolism were observed.

Conclusion

The observed toxicities were acceptable to continue enrollment toward the overall target group of 70 patients. Preliminary efficacy analysis shows encouraging mean progression-free survival. At this time data are not sufficient to encourage routine off-label use of BV combined with TMZ/RT in the setting of newly diagnosed glioblastoma without longer follow-up, enrollment of additional patients, and thorough efficacy assessment.

Bevacizumab, Newly diagnosed glioblastoma, Temozolomide, Radiation, Antiangiogenesis