A North American brain tumor consortium (NABTC 99-04) phase II trial of temozolomide plus thalidomide for recurrent glioblastoma multiforme.
BACKGROUND
Laboratory and clinical data suggest that the anti-angiogenic agent, thalidomide, if combined with cytotoxic agents, may be effective against recurrent glioblastoma multiforme (GBM).


OBJECTIVE
To determine 6-month progression-free survival (6PFS) and toxicity of temozolomide plus thalidomide in adults with recurrent GBM.


METHODS
Eligible patients had recurrent GBM after surgery, radiotherapy, and/or adjuvant chemotherapy. Temozolomide was given at 150-200 mg/m(2)/day on days 1-5 of each 28-day cycle. Thalidomide was given orally at 400 mg at bedtime (days 1-28) and increased to 1,200 mg as tolerated. Patients were evaluated with magnetic resonance imaging scans every 56 days. The study was designed to detect an increase of the historical 6PFS for GBM from 10 to 30%.


RESULTS
Forty-four patients were enrolled, 43 were evaluable for efficacy and safety. The study population included 15 women, 29 men; median age was 53 years (range 32-84); median Karnofsky performance status was 80% (range 60-100%). Thirty-six (82%) patients were chemotherapy-naïve. There were 57 reports of toxicity of grade 3 or greater. Non-fatal grade 3-4 granulocytopenia occurred in 15 patients (34%). The objective response rate was 7%. The estimated probability of being progression-free at 6 months with this therapy is 24% [95% confidence interval (C.I.) 12-38%]. The median time to progression is 15 weeks (95% C.I. 10-20 weeks). There was no observed correlation between serum levels of vascular endothelial growth factor, basic fibroblast growth factor, and IL-8 and the 6PFS outcome.


CONCLUSIONS
This drug combination was reasonably safe, but with little indication of improvement compared to temozolomide alone.
Groves
Morris D
MD
Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, 1400 Holcombe, 431, Houston, TX, 77030, USA. mgroves@mdanderson.org
Puduvalli
Vinay K
VK
Chang
Susan M
SM
Conrad
Charles A
CA
Gilbert
Mark R
MR
Tremont-Lukats
Ivo W
IW
Liu
Ta-Jen
TJ
Peterson
Pamela
P
Schiff
David
D
Cloughesy
Timothy F
TF
Wen
Patrick Y
PY
Greenberg
Harry
H
Abrey
Lauren E
LE
DeAngelis
Lisa M
LM
Hess
Kenneth R
KR
Lamborn
Kathleen R
KR
Prados
Michael D
MD
Yung
W K Alfred
WK
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D018572:Disease-Free Survival; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009656:North America; D016019:Survival Analysis; D000077204:Temozolomide; D013792:Thalidomide / Q000627:therapeutic use
D013792:Thalidomide; D003606:Dacarbazine; D000077204:Temozolomide