Phase II study of temozolomide, thalidomide, and celecoxib for newly diagnosed glioblastoma in adults.

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1: Neuro Oncol. 2008 Jun;10(3):300-8. Epub 2008 Apr 10.

Phase II study of temozolomide, thalidomide, and celecoxib for newly diagnosed glioblastoma in adults.
 
Kesari S, Schiff D, Henson JW, Muzikansky A, Gigas DC, Doherty L, Batchelor TT, Longtine JA, Ligon KL, Weaver S, Laforme A, Ramakrishna N, Black PM, Drappatz J, Ciampa A, Folkman J, Kieran M, Wen PY.
Dana-Farber/Brigham and Women's Cancer Center, Center for Neuro-Oncology, 44 Binney St., SW430D, Boston, MA 02115, USA.
We
conducted a phase II study of the combination of temozolomide and
angiogenesis inhibitors for treating adult patients with newly
diagnosed glioblastoma. Patients who had stable disease following
standard radiation therapy received temozolomide for 5 days in 28-day
cycles, in combination with daily thalidomide and celecoxib.
Patients
were treated until tumor progression or development of unacceptable
toxicity. Four-month progression-free survival (PFS) from study
enrollment was the primary end point, and overall survival (OS) was the
secondary end point. In addition, we sought to correlate response with
O(6)-methylguanine-DNA methyltransferase promoter methylation status
and serum levels of angiogenic peptides.
Fifty patients with
glioblastoma were enrolled (18 women, 32 men). Median age was 54 years
(range, 29-78) and median KPS score was 90 (range, 70-100). From study
enrollment, median PFS was 5.9 months (95% confidence interval [CI]:
4.2-8.0) and 4-month PFS was 63% (95% CI: 46%-75%). Median OS was 12.6
months (95% CI: 8.5-16.4) and 1-year OS was 47%.
 
Of the 47 patients
evaluable for best response, none had a complete response, five (11%)
had partial response, four (9%) had minor response, 22 (47%) had stable
disease, and 16 (34%) had progressive disease. Analysis of serial serum
samples obtained from 47 patients for four angiogenic peptides failed
to show a significant correlation with response or survival for three
of the peptides; higher vascular endothelial growth factor levels
showed a trend toward correlation with decreased OS (p=0.07) and PFS
(p=0.09). The addition of celecoxib and thalidomide to adjuvant
temozolomide was well tolerated but did not meet the primary end point
of improvement of 4-month PFS from study enrollment.