Newly diagnosed glioblastoma multiforme with unmethylated MGMT promoter has a 
poor prognosis, with a median survival of 12 months. This phase II study 
investigated the efficacy and safety of combining the selective integrin 
inhibitor cilengitide with a combination of metronomic temozolomide and 
procarbazine for these patients. Eligible patients (newly diagnosed, 
histologically confirmed supratentorial glioblastoma with unmethylated MGMT 
promoter) were entered into this multicentre study. Cilengitide (2000 mg IV 
twice weekly) was commenced 1 week prior to radiotherapy combined with daily 
temozolomide (60 mg/m(2)) and procarbazine (50 or 100 mg) and, after 4 weeks' 
break, followed by six adjuvant cycles of temozolomide (50-60 mg/m(2)) and 
procarbazine (50 or 100 mg) on days 1-20, every 28 days. Cilengitide was 
continued for up to 12 months or until disease progression or unacceptable 
toxicity. The primary endpoint for efficacy was a 12-month overall survival rate 
of 65 %. Twenty-nine patients completed study treatment. Sixteen patients 
survived for 12 months or more, an overall survival rate of 55 %. The median 
overall survival was 14.5 months (95 % CI 11.1-19.6) and the median 
progression-free survival was 7.4 months (95 % CI 6.1-8). Cilengitide combined 
with metronomic temozolomide and procarbazine in MGMT-promoter unmethylated 
glioblastoma did not improve survival compared with historical data and does not 
warrant further investigation.