Bevacizumab and dose-intense temozolomide in recurrent high-grade glioma

Verhoeff, J.; Lavini, Cristina; Linde, Myra E. van; Stalpers, Lukas J.A.; Majoie, Charles B; Reijneveld, Jaap C.; Furth, Wouter R. van; Richel, D. J.

doi:10.1093/annonc/mdp591

Cited by 81 publications

(57 citation statements)

References 24 publications

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“…Bevacizumab was extensively examined in clinical trials for treatment of recurrent as well as newly-diagnosed GBM, as a single agent and in various combinations with CHT and other targeted therapeutics (71,(78)(79)(80)(81)(82)(83). Bevacizumab gained accelerated approval by the US Food and Drug Administration (FDA) for the treatment of recurrent GBM in 2009 based on a high radiographic response rates and prolonged PFS (84).…”

Section: Inhibition Of Angiogenesis In Gbmmentioning

confidence: 99%

Advances in Experimental Targeted Therapy and Immunotherapy for Patients with Glioblastoma Multiforme

et al. 2017

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Abstract. Glioblastoma multiforme (GBM) represents the most malignant primary brain tumor in adults with generally dismal prognosis, early clinical deterioration and high mortality. GBM is extremely invasive, characterized by intense and aberrant vascularization and high resistance to multimodal treatment. Standard therapy (surgery, radiotherapy and chemotherapy with temozolomide) has very limited effectiveness, with median overall survival of patients no longer than 15 months. Progress in genetics and epigenetics of GBM over the past decade has revealed various aberrations in cellular signaling pathways, the tumor microenvironment, and pathological angiogenesis. A number of targeted anticancer drugs, such as small-molecule kinase inhibitors and monoclonal antibodies, have been evaluated in clinical trials with newly-diagnosed, as well as recurrent GBM. Unfortunately, to date, only a single antiangiogenic agent, bevacizumab, has been approved for the treatment of recurrent GBM in the USA and Canada. The novel possibilities of cancer immunotherapy, especially immune checkpoint inhibitors, are being evaluated in clinical trials of patients with GBM. The most recent clinical experiences with targeted therapy as well as immunotherapy of GBM are given in this review. The relative lack of success of some of these approaches recently revealed in well-designed randomized clinical trials is also discussed.Glioblastoma multiforme (GBM) belongs to the largest group of primary central nervous system (CNS) tumors, so-called gliomas, which are formed from supporting glial cells in the brain parenchyma (1, 2). GBM represents the most common and most malignant tumor in this class, with an incidence of 3-4/100,000/year (3, 4). GBM is an extremely invasive and difficult to treat tumor, characterized by intense and aberrant vascularization and high resistance to radiotherapy (RT) and chemotherapy (CHT). The current standard of care for patients with newly-diagnosed GBM comprises of neurosurgery and subsequent concomitant chemoradiotherapy by fractionated external-beam RT and systemic temozolomide followed by systemic temozolomide in the adjuvant setting (5). There are only very limited possibilities for the treatment of subsequent recurrences, generally with minimal clinical efficacy (6). Despite intensive multimodal treatment strategies, the median survival of patients with GBM is still 12.1-14.6 months and only 3-5% of patients survive longer than 3 years (7).Enormous progress has been made in the genetics and epigenetics of GBM during the past decade. The Cancer 21Τhis article is freely accessible online.Correspondence to: Jiri Polivka, Department of Neurology, Faculty Hospital Plzen, alej Svobody 80, 304 60, Plzen, Czech Republic. E-mail: polivka@fnplzen.cz Key Words: Glioblastoma multiforme, GBM, targeted therapy, immunotherapy, immune checkpoint inhibitors, PD1 inhibition, CTLA4 inhibition, clinical trials, personalized medicine, review. ANTICANCER RESEARCH 37: 21-34 (2017) [8][9][10][11][12]. The most important genetic...

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Section: Inhibition Of Angiogenesis In Gbmmentioning

confidence: 99%

Advances in Experimental Targeted Therapy and Immunotherapy for Patients with Glioblastoma Multiforme

et al. 2017

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“…Beyond the randomized trial leading to the approval of TMZ mentioned above, two other randomized trials with TMZ monotherapy as one of the treatment arms have been published, a direct comparison with the combination of procarbazine, lomustine and vincristine (PCV) before TMZ became first-line standard [69] and a negative trial for the epidermal growth factor recetor (EGFR) tyrosine kinase inhibitor afatinib [70] ( Table 2 and The anti-vascular endothelial growth factor (VEGF) antibody bevacizumab [72][73][74][75], interferon-α2b [76], the multikinase inhibitor sorafenib [77], O6-benzylguanine [78], irinotecan [79], cisplatin [80,81], liposomal doxorubicine [82] and ABT-414, an EGFR-targeted antibody-drug conjugate conjugated to monomethylauristatin F [83].…”

Section: Temozolomide Monotherapy and Combination Regimensmentioning

confidence: 99%

“…Surprisingly, the combination of bevacizumab with TMZ [72][73][74][75] seems less promising than the combination with nitrosoureas [54,58,59]. However, no direct comparisons are available and the trials evaluating bevacizumab plus temozolomide were conducted in part in highly pretreated patient populations [72][73][74].…”

Section: Bevacizumab Monotherapy and Combination Regimensmentioning

confidence: 99%

“…However, no direct comparisons are available and the trials evaluating bevacizumab plus temozolomide were conducted in part in highly pretreated patient populations [72][73][74]. Five phase II trials evaluated the combination of irinotecan with bevacizumab [91][92][93][94][95], two trials added a third combination partner, cetuximab [96] or carboplatin [97].…”

Section: Bevacizumab Monotherapy and Combination Regimensmentioning

confidence: 99%

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Therapeutic options in recurrent glioblastoma—An update

Seystahl

Wick

Weller

2016

Critical Reviews in Oncology/Hematology

177

134

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“…Numerous other studies evaluated TMZ-based combination regimens in rGBM but have failed to deliver conclusive efficacy beyond single-agent activity of TMZ. Those combination partners prospectively evaluated in single-arm designs were bevacizumab, interferon-α2b, sorafenib, O6-benzylguanine, irinotecan, cisplatin, liposomal doxorubicine, and ABT-414 (146)(147)(148)(149)(150)(151)(152)(153)(154)(155)(156)158).…”

Section: Temozolomide Monotherapy and Combination Regimensmentioning

confidence: 99%

Current Standards of Care in Glioblastoma Therapy

et al. 2017

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Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. Regardless of ideal multidisciplinary treatment, including maximal surgical resection, followed by radiotherapy plus concomitant and maintenance temozolomide (TMZ), almost all patients experience tumor progression with nearly universal mortality and a median survival of less than 15 months. The addition of bevacizumab to standard treatment with TMZ revealed no increase in overall survival (OS) but improved progression-free survival (PFS). In newly diagnosed GBM, methylation of the O6-methylguanine-DNA methyltransferase (MGMT) promoter has been shown to predict response to alkylating agents, as well asgnosis. Therefore, MGMT promoter status may have a crucial role in the choice of single modality treatment in fragile elderly population. No standard of care is established in recurrent or progressive GBM. Treatment alternatives may include supportive care, surgery, re-irradiation, systemic therapies, and combined modality therapy. Despite numerous clinical trials, the identification of effective therapies is complex because of the lack of appropriate control arms, selection bias, small sample sizes, and disease heterogeneity. Tumor-treating fields plus TMZ represent a major advance in the field of GBM therapy, and should be Standards of Care in Glioblastoma Therapy 198 considered for patients with newly diagnosed GBM with no contraindications. As a disease with such a poor prognosis, treatment of GBM should go beyond improving survival and aim at preserving and even improving the quality of life of both the patient and the caregiver.

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Bevacizumab and dose-intense temozolomide in recurrent high-grade glioma

Abstract: Treatment with bevacizumab and TMZ is feasible and well tolerated but did not improve PFS6 and median OS.

Cited by 81 publications

References 24 publications

Advances in Experimental Targeted Therapy and Immunotherapy for Patients with Glioblastoma Multiforme

Advances in Experimental Targeted Therapy and Immunotherapy for Patients with Glioblastoma Multiforme

Therapeutic options in recurrent glioblastoma—An update

Current Standards of Care in Glioblastoma Therapy

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