Gliadel (BCNU) wafer plus concomitant temozolomide therapy after primary resection of glioblastoma multiforme

Abstract

Object Gliadel (BCNU) wafer and concomitant temozolomide (TMZ) therapy, when used individually as adjuvant therapies, extend survival from that achieved by resection and radiation therapy (XRT) for glioblastoma multiforme (GBM). It remains unstudied whether combining Gliadel and TMZ therapy is safe or further improves survival in patients with newly diagnosed GBM. The authors reviewed their initial experience utilizing combined Gliadel, TMZ, and radiation therapy for the treatment of GBM. Methods All cases involving patients undergoing primary resection of GBM with or without Gliadel wafer (3.85% BCNU) implantation and adjuvant XRT over a 10-year period (1997–2006) were retrospectively reviewed. Beginning in 2004, concomitant TMZ became the standard of care at the authors’ institution and all patients with Gliadel implantation also received concomitant TMZ (Stupp protocol). Overall survival and treatment-related morbidity were assessed for all patients treated with Gliadel plus concomitant TMZ (XRT + Gliadel + TMZ). Age-matched (≤ 70 years) comparison of survival and morbidity was performed between the XRT + Gliadel + TMZ (post-2003) and XRT + Gliadel (pre-2004) cohorts. Results Thirty-three patients were treated with XRT + Gliadel + TMZ. The median survival in this group was 20.7 months, with a 2-year survival rate of 36%. Six-month morbidity included surgical site infection in 1 case (3%), perioperative seizures in 2 cases (6%), deep-vein thrombus in 1 (3%), pulmonary embolism in 3 (9%), and cerebral edema requiring admission for intravenous dexamethasone in 1 case (3%). Myelosuppression required premature termination of TMZ in 7 patients (21%) (thrombocytopenia in 5, neutropenia in 2 cases). In patients ≤ 70 years of age, XRT + Gliadel + TMZ (30 patients, post-2003) was independently associated with improved median survival (21.3 vs 12.4 months, p = 0.005) versus XRT + Gliadel (78 patients, pre-2004), with 2-year survival of 39 versus 18%, respectively. In these patients, XRT + Gliadel + TMZ was not associated with an increase in perioperative morbidity in comparison with XRT + Gliadel. Conclusions In this experience, concomitant TMZ therapy in addition to Gliadel wafer implantation was associated with a median survival of nearly 21 months without increased perioperative morbidity. Temozolomide can be safely administered to patients receiving Gliadel wafers after resection of GBM.

Intracranial microcapsule chemotherapy delivery for the localized treatment of rodent metastatic breast adenocarcinoma in the brain

“…Localized drug delivery devices provide high drug concentrations to the tumor site while preventing drug degradation and clearance until its release (7,8). The efficacy of current intracranial drug delivery, such as Carmustine wafers, has promise, with a doubling of median survival from 9 to 20 mo in the case of Carmustine wafers (6,9,10). Phase III trial data indicated a 2-to 3-mo survival advantage in Carmustine wafers-treated patients (11), and Carmustine wafers continue to have a role combined with radiation and oral temozolomide (TMZ).…”

High-grade glial tumors, survival & prognostic factors; 5-year experience from Ankara Oncology Hospital

“…tarafından bu protokol ile tedavi edilen 33 hastada medyan sağkalım yaklaşık 20.7 ay ve iki yıllık sağkalım %36 bulunmuştur. [23] Bu sağkalım avantajı başka geriye dönük çalışmalarda da ortaya konmuştur. [24] Lokal ve sistemik tedavi kombinasyonu umut verici görünmekle birlikte standart olarak uygulanabilmesi için daha fazla ileriye yönelik çalışmaya ihtiyaç vardır.…”

Controversies in the Adjuvant Therapy of High-Grade Gliomas

“…A retrospective study of 33 patients who received carmustine wafers in addition to standard chemoradiation suggested that the treatments can be combined safely. The median survival duration of these patients, who, by definition, all had extensive surgical debulking, was nearly 21 months [17]. A large prospective randomized trial is needed to clearly document the added survival benefit of carmustine wafers to standard therapy in this patient population.…”