A phase II study of thalidomide and irinotecan for treatment of glioblastoma multiforme.
OBJECTIVE
Irinotecan is a cytotoxic agent with activity against gliomas. Thalidomide, an antiangiogenic agent, may play a role in the treatment of glioblastoma multiforme (GBM). To evaluate the combination of thalidomide and irinotecan, we conducted a phase II trial in adults with newly-diagnosed or recurrent GBM.


METHODS
Thalidomide was given at a dose of 100 mg/day, followed by dose escalation every 2 weeks by 100 mg/day to a target of 400 mg/day. Irinotecan was administered on day 1 of each 3 week cycle. Irinotecan dose was 700 mg/m(2) for patients taking enzyme-inducing anticonvulsants and 350 mg/m(2) for all others. The primary endpoint was tumor response, assessed by MRI. Secondary endpoints were toxicity, progression-free survival, and overall survival.


RESULTS
Twenty-six patients with a median age of 55 years were enrolled, with fourteen evaluable for the primary outcome, although all patients were included for secondary endpoints. One patient (7%) exhibited a partial response after twelve cycles, and eleven patients (79%) had stable disease. The intention to treat group with recurrent disease included 16 patients who had a 6-month PFS of 19% (95% CI: 4-46%) and with newly-diagnosed disease included 10 patients who had a 6-month PFS of 40% (95% CI: 12-74%). Gastrointestinal (GI) toxicity was mild, but six patients (23%) experienced a venous thromboembolic complication. Two patients had Grade 4 treatment-related serious adverse events that required hospitalization. There were no treatment-related deaths.


CONCLUSIONS
The combination of irinotecan and thalidomide has limited activity against GBM. Mild GI toxicity was observed, but venous thromboembolic complications were common.
Fadul
Camilo E
CE
Department of Medicine, Section of Hematology/Oncology, Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center Drive, One Medical Center Drive, Lebanon, NH 03756, USA. camilo.e.fadul@hitchcock.org
Kingman
Linda S
LS
Meyer
Louise P
LP
Cole
Bernard F
BF
Eskey
Clifford J
CJ
Rhodes
C Harker
CH
Roberts
David W
DW
Newton
Herbert B
HB
Pipas
J Marc
JM
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016543:Central Nervous System Neoplasms / Q000188:drug therapy*; D018450:Disease Progression; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D013792:Thalidomide / Q000008:administration & dosage*
D007166:Immunosuppressive Agents; D013792:Thalidomide; D000077146:Irinotecan; D002166:Camptothecin