OBJECTIVE: Recently a randomized placebo-controlled phase III trial of 
biodegradable polymers containing carmustine has demonstrated a significant 
survival benefit for patients treated with local chemotherapy. A local 
chemotherapy applied directly to the resection cavity may act directly on 
residual tumor cells in adjacent brain possibly leading to a local control of 
the tumor and increased survival.
METHODS: We have analyzed the pattern of recurrence using serial MRI studies of 
24 patients treated with GLIADEL Wafers or placebo wafers following resection of 
glioblastomas.
RESULTS: Of 24 patients 11 received carmustine wafers and 13 placebo. The age 
distribution and Karnowsky performance scores of the two populations were not 
different. However, the median survival (14.7 versus 9.5 months; P = 0.007) and 
the time to neurological deterioration (12.9 +/- 4.85 vs. 9.4 +/- 2.73 months; P 
= 0.035) was significantly longer in the treatment group versus the placebo 
treated control. Preoperative and follow up MRI studies were evaluated in a 
blinded fashion. Out of 24 patients that entered the analysis 11 showed 
clearance of all contrast enhancement following resection of glioblastomas. 
Seventeen tumors progressed locally and 7 showed different patterns of distant 
failure. Within the carmustine treated group 8 patients showed a local treatment 
failure with recurrent tumors immediately adjacent to the resection cavity or 
progression form a residual tumor. Three patients showed a multifocal distant 
and local pattern of failure after complete or subtotal removal. In no case the 
local chemotherapy resulted in a distant recurrence only. However, the time to 
radiographic progression was 165.1 +/- 80.75 days for the GLIADEL Wafer group 
and 101.9 +/- 43.06 days for the placebo group (P = 0.023).
CONCLUSION: In this subgroup analysis of a phase III trial population both the 
clinical progression and radiological progression were significantly delayed in 
patients treated with local chemotherapy, resulting in an increased survival 
time. Local chemotherapy with carmustine containing wafer implants did not 
result in an altered pattern of recurrence and did not promote multifocal 
patterns of recurrence.