Sponsored by
Int J Radiat Oncol Biol Phys. 2008 Mar 18 [Epub ahead of print]
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.
Graham C, Yong WH, Mischel P, Liau LM, Bergsneider M, Pope W, Selch
M, Cloughesy T.
Department of Neurology, David Geffen School of Medicine at
University of California-Los Angeles, Los Angeles, CA.
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/m(2) 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/m(2) 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 approximately 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/pulmonar
CONCLUSION: The observed toxicities were acceptable to continue enrollment toward the overall
target group of 70 patients. Preliminary efficacy analysis shows
encouraging mean progression-
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.