26 december 2010: Bron: Neurosurg Rev. 2010 October; 33(4): 441–449. Published online 2010 August 13. doi: 10.1007/s10143-010-0280-7.

Chemo toedienen met zogenoemde wafers (inwendig geplaatste soort ballonnetjes die timereleased chemo afgeven) lijkt beetje succes te hebben bij hersentumoren. Aanvullend op studieresultaten uit 2006, zie hieronder, is recent een nieuw studieresultaat vrijgekomen. Daar wordt de nadruk gelegd op de bijwerkingen zeker als deze wafertechniek wordt gevolgd door andere chemokuren en bestralling. Toch lijkt deze aanpak te prevaleren boven systemische chemo aldus de onderzoekers al moeten de omstandigheden wel optimaal gemaakt worden. Wat die moeten zijn lees het studierapport. Wij plaatsen hier het abstract maar als u hier klikt kunt u het volledige studierapport lezen.

Neurosurg Rev. 2010 Oct;33(4):441-9. Epub 2010 Aug 13.

First-line treatment of malignant glioma with carmustine implants followed by concomitant radiochemotherapy: a multicenter experience.

Bock HC, Puchner MJ, Lohmann F, Schütze M, Koll S, Ketter R, Buchalla R, Rainov N, Kantelhardt SR, Rohde V, Giese A.

Department of Neurosurgery, Center of Neurological Medicine, University of Göttingen, Göttingen, Germany.

Abstract

Randomized phase III trials have shown significant improvement of survival 1, 2, and 3 years after implantation of 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) wafers for patients with newly diagnosed malignant glioma. But these studies and subsequent non-phase III studies have also shown risks associated with local chemotherapy within the central nervous system. The introduction of concomitant radiochemotherapy with temozolomide (TMZ) has later demonstrated a survival benefit in a phase III trial and has become the current treatment standard for newly diagnosed malignant glioma patients. Lately, this has resulted in clinical protocols combining local chemotherapy with BCNU wafers and concomitant radiochemotherapy with TMZ although this may carry the risk of increased toxicity. We have compiled the treatment experience of seven neurosurgical centers using implantation of carmustine wafers at primary surgery followed by 6 weeks of radiation therapy (59-60 Gy) and 75 mg/m(2)/day TMZ in patients with newly diagnosed glioblastoma followed by TMZ monochemotherapy. We have retrospectively analyzed the postoperative clinical course, occurrence and severity of adverse events, progression-free interval, and overall survival in 44 patients with newly diagnosed glioblastoma multiforme. All patients received multimodal treatment including tumor resection, BCNU wafer implantation, and concomitant radiochemotherapy. Of 44 patients (mean age 59 ± 10.8 years) with glioblastoma who received Gliadel wafer at primary surgery, 28 patients (64%) had died, 16 patients (36%) were alive, and 15 patients showed no evidence of clinical or radiographic progression after a median follow-up of 15.6 months. At time of analysis of adverse events in this patient population, the median overall survival was 12.7 months and median progression-free survival was 7.0 months. Surgical, neurological, and medical adverse events were analyzed. Twenty-three patients (52%) experienced adverse events of any kind including complications that did not require treatment. Nineteen patients (43%) experienced grade 3 or grade 4 adverse events. Surgical complications included cerebral edema, healing abnormalities, cerebral spinal fluid leakage, meningitis, intracranial abscess, and hydrocephalus. Neurological adverse events included newly diagnosed seizures, alteration of mental status, and new neurological deficits. Medical complications were thromboembolic events (thrombosis, pulmonary embolism) and hematotoxicity. Combination of both treatment strategies, local chemotherapy with BCNU wafer and concomitant radiochemotherapy, appears attractive in aggressive multimodal treatment schedules and may utilize the sensitizing effect of TMZ and carmustine on MGMT and AGT on their respective drug resistance genes. Our data demonstrate that combination of local chemotherapy and concomitant radiochemotherapy carries a significant risk of toxicity that currently appears underestimated. Adverse events observed in this study appear similar to complication rates published in the phase III trials for BCNU wafer implantation followed by radiation therapy alone, but further add the toxicity of concomitant radiochemotherapy with systemic TMZ. Save use of a combined approach will require specific prevention strategies for multimodal treatments.

PMID: 20706757 [PubMed - in process]PMCID: PMC2936684

10 mei 2006: Bron: http://www.springerlink.com

Het aanvullend toedienen van een plaatselijke 'timereleased' chemo voor, tijdens en na een operatie van hersentumoren (glioma's) en bestraling geeft een aanzienlijke levensverlenging blijkt uit een gerandomiseerde placebo gecontroleerde fase III studie in meerdere ziekenhuizen. Uiteindelijk bleken 59 patiënten van de startende 240 deelnemers aan de studie evalueerbaar na 2 en 3 jaar. We tekenen er wel bij aan dat deze studie ook al in 2002 werd gepubliceerd, zie onder chemo bij en nu dus weer opnieuw actueel als nieuws gebracht. Wat de reden hiervan is durven we niet te zeggen.

Van de 59 patienten welke beschikbaar waren voor een langdurige follow-up waren er nog 11 in leven na 56 maanden, 9 daarvan hadden de chemo BCNU wafers gehad en 2 hadden een placebo wafers gehad. Mediane overlevingstijd van de patiënten behandeld met BCNU wafers was 13.8 maanden vs 11.6 maanden in placebo-behandelde groep patiënten (P = 0.017) met een hazard ratio van 0.73 (P = 0.018), dat een significant 27% verminderd risico betekent. Dit overlevingsvoordeel was bereikt op zowel 1, 2 en 3 jaars meting en is statistisch significant (P = 0.01) na 3 jaar. Twee van de 207 GBM patiënten bleek nog te steeds in leven aan het eind van de studie follow-up, beide kwamen uit de BCNU wafer behandelingsgroep.

Conclusie.
Patienten met kwaadaardige hersentumoren (glioma's) behandeld met BCNU wafers op het moment van de start van de operatie in combinatie met bestraling levert een significant langere overlevingstijd na 2 en 3 jaar follow-up in vergelijking met placebo als aanvulling op een operatie en bestraling.

Gliadel®wafer in initial surgery for malignant glioma: long-term follow-up of a multicenter controlled trial M. Westphal1, Z. Ram2, V. Riddle3, D. Hilt4, E. Bortey5 and On behalf of the Executive Committee of the Gliadel® Study Group
(1) Department of Neurosurgery, University Hospital Eppendorf, Hamburg, Germany
(2) Department of Neurosurgery, Tel Aviv Sourasky Medical Center, Tel Aviv, Turkey
(3) Pharm Athene, Inc., Maryland, USA
(4) Ascend Therapeutics, VA, USA
(5) Athero Genics, Inc., Georgia, USA

Received: 3 December 2004 Accepted: 3 November 2005 Published online: 17 February 2006

Summary Objective.
Adjuvant systemic chemotherapy increases survival of primary malignant glioma patients beyond 12–18 months. The only interstitial chemotherapy treatment approved for malignant glioma is Gliadel® wafer containing carmustine (BCNU) placed in the resection cavity at surgery. Analysis of a large trial by Westphal and colleagues (n = 240) showed a 29% risk reduction (P = 0.03) in the BCNU wafer-treated group over the course of the 30-month trial. Long-term follow-up of these patients was undertaken to determine the survival benefit at 2 and 3 years.

Methods.
Survival proportions for the placebo and treatment groups over the 56-month study were estimated by the Kaplan-Meier method. Multiple-regression analyses using the Cox proportional hazards model included prognostic factors of age, KPS, and tumor type. A secondary analysis was conducted for 207 GBM patients.

Results.
Of the 59 patients available for long-term follow-up, 11 were alive at 56 months: 9 had received BCNU wafers and 2 had received placebo wafers. Median survival of patients treated with BCNU wafers was 13.8 months vs 11.6 months in placebo-treated patients (P = 0.017) with a hazard ratio of 0.73 (P = 0.018), representing a 27% significant risk reduction. This survival advantage was maintained at 1, 2, and 3 years and was statistically significant (P = 0.01) at 3 years. Two of 207 GBM patients remained alive at the end of the follow-up period, both in the BCNU wafer-treated group. Conclusion. Malignant glioma patients treated with BCNU wafers at the time of initial surgery in combination with radiation therapy demonstrated a survival advantage at 2 and 3 years follow-up compared with placebo. Keywords: BCNU; brain neoplasms; carmustine; chemotherapy; glioblastoma multiforme; Kaplan-Meier; malignant glioma; neurosurgery; survival analysis Source: http://www.springerlink.com/(1joknsji1rk0zlqwlmsgaiee)/app/home/contribution.asp?referrer=parent&backto=issue,3,23;journal,4,426;linkingpublicationresults,1:102025,1