Local alkylating chemotherapy applied immediately after 5-ALA guided resection of glioblastoma does not provide additional benefit

Sage, William; Guilfoyle, Mathew R.; Luney, Catriona; Young, Adam M. H.; Sinha, Rohitashwa; Sgubin, Donatella; McAbee, Joseph H.; Ma, Roy; Jefferies, Sarah; Jena, R.; Harris, Frances; Allinson, Kieren; Matys, Tomasz; Qian, Wendi; Santarius, Thomas; Price, Stephen J.; Watts, Colin

doi:10.1007/s11060-017-2649-8

Cited by 22 publications

(24 citation statements)

References 35 publications

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“…Since 2005, one pivotal clinical trial defined the radiotherapy and temozolomide combination (RT–temozolomide) as the standard of care in patients with newly-diagnosed GBM, for patients 18–70 years old with a WHO performance status of ≤ 2 [ 6 ]. Carmustine wafer (CW) is an option when maximal safe resection (RS) is performed and high grade glioma is histologically proven [ 11 – 14 ]. More recently, bevacizumab in combination with RT–temozolomide in first-line treatment showed a significant prolonged progression-free survival but failed to demonstrate a significant overall survival (OS) benefit [ 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Association of patterns of care, prognostic factors, and use of radiotherapy–temozolomide therapy with survival in patients with newly diagnosed glioblastoma: a French national population-based study

et al. 2018

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Background Glioblastoma is the most frequent primary malignant brain tumor. In daily practice and at whole country level, oncological care management for glioblastoma patients is not completely known. Objectives To describe oncological patterns of care, prognostic factors, and survival for all patients in France with newly-diagnosed and histologically confirmed glioblastoma, and evaluate the impact of extended temozolomide use at the population level. Methods Nationwide population-based cohort study including all patients with newly-diagnosed and histologically confirmed glioblastoma in France in 2008 and followed until 2015. Results Data from 2053 glioblastoma patients were analyzed (male/female ratio 1.5, median age 64 years). Median overall survival (OS) was 11.2 [95% confidence interval (CI) 10.7–11.9] months. The first-line therapy and corresponding median survival (MS, in months) were: 13% did not receive any oncological treatment (biopsy only) (MS = 1.8, 95% CI 1.6–2.1), 27% received treatment without the combination of radiotherapy (RT)–temozolomide (MS = 5.9, 95% CI 5.5–6.6), 60% received treatment including the initiation of the concomitant phase of RT–temozolomide (MS = 16.4, 95% CI 15.2–17.4) whom 44% of patients initiated the temozolomide adjuvant phase (MS = 18.9, 95% CI 18.0–19.8). Only 22% patients received 6 cycles or more of adjuvant temozolomide (MS = 25.5, 95% CI 24.0–28.3). The multivariate analysis showed that the risk of mortality was significantly higher for the non-progressive patients who stopped at 6 cycles (standard protocol) than those who continued the treatment, hazard ratio = 1.5 (95% CI 1.2–1.9). Conclusion In non-progressive patients, prolonging the adjuvant temozolomide beyond 6 cycles may improve OS. Electronic supplementary material The online version of this article (10.1007/s11060-018-03065-z) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Association of patterns of care, prognostic factors, and use of radiotherapy–temozolomide therapy with survival in patients with newly diagnosed glioblastoma: a French national population-based study

et al. 2018

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“…In the other three RCTs, implantation of carmustine was not randomized and was decided according to clinical conditions (6,20,21). The comparability of one cohort study is obscure (22), while that of others is relatively distinct (23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34). The results of the methodological quality assessment using NOS and Jadad scale are also shown in Table 1.…”

Section: Characteristics Of the Studiesmentioning

confidence: 99%

“…Next, we investigated whether the addition of carmustine therapy as a supplement to STUPP protocol could confer more significant survival benefits for GBM patients. There were only two studies that reported the comparison of survival benefits between patients with TMZ chemotherapy and TMZ plus carmustine chemotherapy (25,33). The analysis of the two studies showed that GBM patients receiving combined chemotherapy (carmustine plus TMZ) had longer OS than those receiving TMZ alone (HR = 0.78, 95% CI = 0.63-0.97, P = 0.02, I 2 = 0%) ( Figure 3C).…”

Section: Association Between Carmustine Treatment and Survival Of Glimentioning

confidence: 99%

Carmustine as a Supplementary Therapeutic Option for Glioblastoma: A Systematic Review and Meta-Analysis

et al. 2020

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Background: Glioblastoma (GBM) is the most aggressive type of primary malignant brain tumor. Carmustine is used by intravenous injection or local implantation in the resection cavity for gliomas, including GBMs. However, the therapeutic potential of carmustine is not well-recognized. This analysis aimed to evaluate the survival benefits of carmustine in glioma patients, especially those with GBM. Methods: Randomized controlled trials (RCTs) and cohort studies regarding carmustine for glioma treatment were searched in PubMed, the Cochrane Library, and Embase from January 1979 to March 2020. Quality assessment was conducted with Jadad and Newcastle-Ottawa scales (NOS). Statistical analysis was conducted by the Revman 5.3 software. Results: Twenty-two eligible RCTs and cohort studies involving 5,821 glioma patients were included. Overall, glioma patients receiving carmustine as an adjuvant therapy had better progression-free survival [PFS; hazard ratio (HR) = 0.85, 95% CI = 0.77-0.94, P = 0.002] and overall survival (OS; HR = 0.85, 95% CI = 0.79-0.92, P < 0.0001) than those without carmustine treatment. Subgroup analysis showed that the OS benefit was observed in GBM (HR = 0.84, 95% CI = 0.78-0.91, P < 0.00001) but not in anaplastic glioma patients (HR = 1.20, 95% CI = 0.70-2.07, P = 0.50). Additionally, both newly diagnosed and recurrent GBM patients who received carmustine treatment showed better OS (HR = 0.86, 95% CI = 0.79-0.95, P = 0.002; HR = 0.77, 95% CI = 0.67-0.89, P = 0.0002, respectively). Both carmustine implantation in resection cavity and intravenous administration significantly prolonged OS (HR = 0.84, 95% CI = 0.78-0.92, P < 0.0001; HR = 0.86, 95% CI = 0.75-0.99, P = 0.04, respectively). Moreover, GBM patients receiving a combined carmustine and temozolomide (TMZ) therapy had longer OS than those receiving TMZ alone (HR = 0.78, 95% CI = 0.63-0.97, P = 0.03). Conclusion: Carmustine implantation in resection cavity provides survival benefit for GBM patients, and it may be a promising supplement to standard therapeutic protocol by offering a bridge between surgical resection and onset of TMZ therapy.

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“…While the clinical benefits of BCNU wafers have not greatly ameliorated the tumor burden in GB patients, an abundance of clinical literature using this adjuvant therapy provides key and quantitative lessons for the next generation of local chemotherapy delivery systems. In the development of the underlying material of the wafer technology, a motivational principle was the sustained local delivery of a high chemotherapy concentration within the pharmaceutical window as an adjuvant therapy .…”

Section: Outcomes and Lessons From The Clinicmentioning

confidence: 99%

Designing Next‐Generation Local Drug Delivery Vehicles for Glioblastoma Adjuvant Chemotherapy: Lessons from the Clinic

Tabet

Jensen

Parkins

et al. 2019

Adv Healthcare Materials

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The clinical outcomes and 5-year survival rate for patients with glioblastoma (GB) make it among the most pernicious and challenging diseases to treat. Despite all the resources, time, and talent focused on developing targeted and/or local delivery technologies by the biomaterials community for GB, the clinical performance of the FDA-approved therapy carmustine ((BCNU)-loaded polyanhydride wafers) and clinical trials of other material approaches have been discouraging. As disappointing is the remarkably stagnant clinical translation of next-generation material approaches for GB. Despite encouraging preclinical results from hydrogels and modified wafer formulations loaded with more efficacious chemotherapies, a total of zero have completed even a phase I clinical trial. Other strategies, including convection-enhanced delivery, microsphere formulations, or drug-loaded nanoparticles have seen limited, albeit some, translation into the clinic with mixed results. This lackluster progress can be attributed, in part, to the paucity of communication between material scientists, biomedical scientists, and clinicians. When examining the purported clinical relevance of embedding certain material properties into formulations, it is clear that some widely known truths about the nature of GB progression among clinicians have not reached the biomaterials community.Furthermore, a closer examination of the lessons from the BCNU wafers and other clinical trials of GB drug delivery materials may enrich and inspire materials scientists to create new systems that satisfy unmet medical needs identified by the clinical community. In tandem, clinicians and biomedical scientists may benefit from a short review highlighting the biocompatibility, safety, longevity, kinetics, tunability, and efficacy of promising new drug delivery materials without inundation by chemical and physical characterizations or discussions.Another key challenge in treating GB is an incomplete understanding of disease pathophysiology, such as mechanisms driving intrinsic and adaptive GB cell chemoresistance. A combined approach where biomedical scientists and material To date, the clinical outcomes and survival rates for patients with glioblastoma (GB) remain poor. A promising approach to disease-modification involves local delivery of adjuvant chemotherapy into the resection cavity, thus circumventing the restrictions imposed by the blood-brain barrier. The clinical performance of the only FDA-approved local therapy for GB [carmustine (BCNU)-loaded polyanhydride wafers], however, has been disappointing. There is an unmet medical need in the local treatment of GB for drug delivery vehicles that provide sustained local release of small molecules and combination drugs over several months. Herein, key quantitative lessons from the use of local and systemic adjuvant chemotherapy for GB in the clinic are outlined, and it is discussed how these can inform the development of next-generation therapies. Several recent approaches are highlighted, and it is proposed that long...

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Local alkylating chemotherapy applied immediately after 5-ALA guided resection of glioblastoma does not provide additional benefit

Cited by 22 publications

References 35 publications

Association of patterns of care, prognostic factors, and use of radiotherapy–temozolomide therapy with survival in patients with newly diagnosed glioblastoma: a French national population-based study

Association of patterns of care, prognostic factors, and use of radiotherapy–temozolomide therapy with survival in patients with newly diagnosed glioblastoma: a French national population-based study

Carmustine as a Supplementary Therapeutic Option for Glioblastoma: A Systematic Review and Meta-Analysis

Designing Next‐Generation Local Drug Delivery Vehicles for Glioblastoma Adjuvant Chemotherapy: Lessons from the Clinic

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