Table 1.

Summary of clinical trials targeting survival and apoptosis pathways in GBM

Target	Drug (s)	Trial design	Study population	Outcome	Ref
EGFR	Erlotinib	Randomised, controlled, phase II #26032	110 Recurrent GBM	6-month PFS: 11.4% vs 24% control, Low akt borderline significance	[34]
	Erlotinib (+RT+TMZ)	Phase I/II cf historical controls #N0177	97 newly diagnosed GBM	Median survival 15.3 months, no benefit at OS	[41]
	Erlotinib (+RT +TMZ)	Phase II cf historical controls	65 newly diagnosed GBM/gliosarcoma	Median survival 19.3 months vs 14.1 controls, positive correlation MGMT methylation with survival and MGMT methylation + PTEN positivity with improved survival	[40]
	Erlotinib (+RT +TMZ)	Phase II	27 newly diagnosed GBM	OS 8.6 months median PFS 2.8 months	[42]
	Erlotinib (+RT+TMZ)	Phase II #NCT00187486	Newly diagnosed GBM/gliosarcoma	Ongoing http://www.clinicaltrials.gov
	Erlotinib single-agent	Phase II open-label, multicenter #NCT00337883	First Relapse GBM	Completed http://www.clinicaltrials.gov
	Gefitinib	Phase II	53 Recurrent GBM	31 patients had radiographic progressive disease within the first 2 months, 51 progressed eventually median EFS: 8.1 weeks	[53]
	Erlotinib +RT+TMZ)	Phase II #NCT00274833	Newly diagnosed GBM	Ongoing http://www.clinicaltrials.gov
Akt	Perifosine	Phase II #NCT00590954	Recurrent/progressive Malignant Gliomas	Ongoing http://www.clinicaltrials.gov
	Perifosine and Temsirolimus	Phase I/II #NCT01051557	Recurrent/progressive Malignant Glioma	Planned, not yet recruiting http://www.clinicaltrials.gov
	Nelfinavir (+TMZ +RT)	Phase I/II #NCT00694837	Newly diagnosed GBM	Recruiting http://www.clinicaltrials.gov
PI3K/mTOR	XL765 +TMZ	Phase I #NCT00704080	Adults Malignant Gliomas
mTOR	Temsirolimus (CCI-779)	Phase II	65 Recurrent GBM	6-month PFS: 7.8% median OS 4.4 months, high levels phospho p70s6K appear to predict benefit of treatment	[60]
	Temsirolimus	Phase II	43 Recurrent GBM	No evidence of efficacy, 1 patient PF at 6-month: 2 PR, 20 SD, median time to progression 9 weeks	[59]
	Temsirolimus (+TMZ+RT)	Phase I #NCT00316849	newly diagnosed GBM	Recruiting http://www.clinicaltrials.gov
	Temsirolimus (+ Erlotinib+ Tipifarnib)	Phase I/II #NCT00335764	recurrent GBM/gliosarcoma.	Recruiting http://www.clinicaltrials.gov
	Everolimus + gefitinib	Phase I/II #NCT00085566	Progressive GBM	Ongoing http://www.clinicaltrials.gov
	Everolimus	Phase I/II Pilot, Multicenter #NCT00515086	Recurrent GBM	Completed, Decemeber 2009
	Everolimus +AEE788	Phase IB/II multicenter, two-Arm, dose-escalation	Recurrent GBM	Ongoing http://www.clinicaltrials.gov
Bcl-2	Gossypol	Phase II #NCT00540722	Recurrent GBM	Ongoing http://www.clinicaltrials.gov
	Gossypol (AT-101) +RT +TMZ vs AT-101 +Adjuvant TMZ	Phase I non-randomised #NCT00390403	Newly diagnosed GBM	Completed, June 2009