The Polifeprosan 20 with carmustine (BCNU, bis-chloroethylnitrosourea, 
Gliadel(®)) polymer implant wafer is a biodegradable compound containing 3.85% 
carmustine which slowly degrades to release carmustine and protects it from 
exposure to water with resultant hydrolysis until the time of release. The 
carmustine implant wafer was demonstrated to improve survival in blinded 
placebo-controlled trials in selected patients with newly diagnosed or recurrent 
malignant glioma, with little increased risk of adverse events. Based on these 
trials and other supporting data, US and European regulatory authorities granted 
approval for its use in recurrent and newly diagnosed malignant glioma, and it 
remains the only approved local treatment. The preclinical and clinical data 
suggest that it is optimally utilized primarily in the proportion of patients 
who may have total or near total removal of gross tumor. The aim of this work 
was to review the evidence for the use of carmustine implants in the management 
of malignant astrocytoma (World Health Organization grades III and IV), 
including newly diagnosed and recurrent disease, especially in the setting of a 
standard of care that has changed since the randomized trials were completed. 
Therapy has evolved such that patients now generally receive temozolomide 
chemotherapy during and after radiotherapy treatment. For patients undergoing 
repeat resection for malignant glioma, a randomized, blinded, placebo-controlled 
trial demonstrated a median survival for 110 patients who received carmustine 
polymers of 31 weeks compared with 23 weeks for 122 patients who only received 
placebo polymers. The benefit achieved statistical significance only on analysis 
adjusting for prognostic factors rather than for the randomized groups as a 
whole (hazard ratio = 0.67, P = 0.006). A blinded, placebo-controlled trial has 
also been performed for carmustine implant placement in newly diagnosed patients 
prior to standard radiotherapy. Median survival was improved from 11.6 to 13.9 
months (P = 0.03), with a 29% reduction in the risk of death. When patients with 
glioblastoma multiforme alone were analyzed, the median survival improved from 
11.4 to 13.5 months, but this improvement was not statistically significant. 
When a Cox's proportional hazard model was utilized to account for other 
potential prognostic factors, there was a significant 31% reduction in the risk 
of death (P = 0.04) in this subgroup. Data from other small reports support 
these results and confirm that the incidence of adverse events does not appear 
to be increased meaningfully. Given the poor prognosis without possibility of 
cure, these benefits from a treatment with a favorable safety profile were 
considered meaningful. There is randomized evidence to support the use of 
carmustine wafers placed during resection of recurrent disease. Therefore, 
although there is limited specific evidence, this treatment is likely to be 
efficacious in an environment when nearly all patients receive temozolomide as 
part of initial management. Given that half of the patients in the randomized 
trial assessing the value of carmustine implants in recurrent disease had 
received prior chemotherapy, it is likely that this remains a valuable treatment 
at the time of repeat resection, even after temozolomide. There are data from 
multiple reports to support safety. Although there is randomized evidence to 
support the use of this therapy in newly diagnosed patients who will receive 
radiotherapy alone, it is now standard to administer both adjuvant temozolomide 
and radiotherapy. There are survival outcome reports for small cohorts of 
patients receiving temozolomide with radiotherapy, but this information is not 
sufficient to support firm recommendations. Based on the rationale and evidence 
of safety, this approach appears to be a reasonable option as more information 
is acquired. Available data support the safety of using carmustine wafers in 
this circumstance, although special attention to surgical guidelines for 
implanting the wafers is warranted.