Bevacizumab Alone at 5 mg/kg in an Every-3-Week Schedule for Patients with Recurrent Glioblastomas: A Single Center Experience

Kaloshi, Gentian; Brace, Gramoz; Rroji, Arben; Bushati, Teona; Roci, Ermir; Hoxha, Mehmet; Fejzo, G.; Petrela, Mentor

doi:10.1177/030089161309900507

Cited by 13 publications

(15 citation statements)

References 13 publications

(13 reference statements)

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“…This comparable efficacy suggests that low dose bevacizumab has activity in recurrent glioblastoma and is a reasonable treatment regimen to investigate. In addition, no grade III-IV toxicities were observed at this low dose 28 . It is possible that low dose bevacizumab may be associated with less toxicity when compared to standard dose bevacizumab.…”

Section: Discussionmentioning

confidence: 73%

“…Low dose single agent bevacizumab dosed 5mg/kg every 3 weeks has been evaluated in a retrospective review of recurrent glioblastoma patients with substantial activity noted (median PFS of 3.6 months and median OS of 6.4 months) comparable to other studies evaluating single agent bevacizumab at higher doses 28 . This comparable efficacy suggests that low dose bevacizumab has activity in recurrent glioblastoma and is a reasonable treatment regimen to investigate.…”

Section: Discussionmentioning

confidence: 94%

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A randomized phase II trial of standard dose bevacizumab versus low dose bevacizumab plus lomustine (CCNU) in adults with recurrent glioblastoma

et al. 2016

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Background Antiangiogenic therapy can rapidly reduce vascular permeability and cerebral edema but high doses of bevacizumab may induce selective pressure to promote resistance. This trial evaluated the efficacy of low dose bevacizumab in combination with lomustine (CCNU) compared to standard dose bevacizumab in patients with recurrent glioblastoma. Methods Patients (N = 71) with recurrent glioblastoma who previously received radiation and temozolomide were randomly assigned 1:1 to receive bevacizumab monotherapy (10 mg/kg) or low dose bevacizumab (5 mg/kg) in combination with lomustine (90 mg/m2). The primary end point was progression-free survival (PFS) based on a blinded, independent radiographic assessment of post-contrast T1-weighted and non-contrast T2/FLAIR weighted magnetic resonance imaging (MRI) using RANO criteria. Results For 69 evaluable patients, median PFS was not significantly longer in the low dose bevacizumab + lomustine arm (4.34 months, CI: 2.96-8.34) compared to the bevacizumab alone arm (4.11 months, CI: 2.69-5.55, p = 0.19). In patients with first recurrence, there was a trend towards longer median PFS time in the low dose bevacizumab + lomustine arm (4.96 months, CI: 4.17-13.44) compared to the bevacizumab alone arm (3.22 months CI: 2.5-6.01, p = 0.08). Conclusions The combination of low dose bevacizumab plus lomustine was not superior to standard dose bevacizumab in patients with recurrent glioblastoma. Although the study was not designed to exclusively evaluate patients at first recurrence, a strong trend towards improved PFS was seen in that subgroup for the combination of low dose bevacizumab plus lomustine. Further studies are needed to better identify such subgroups that may most benefit from the combination treatment.

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Section: Discussionmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 94%

A randomized phase II trial of standard dose bevacizumab versus low dose bevacizumab plus lomustine (CCNU) in adults with recurrent glioblastoma

et al. 2016

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“…A variety of retrospective and prospective studies have evaluated combining BEV with various agents including IRI, etoposide, TMZ, carboplatin, cetuximab, erlotinib, and to date none have proved more effective than BEV only [ Table 12 ]. [ 2 5 57 62 65 79 93 96 100 105 106 119 140 159 195 198 204 205 211 235 236 237 262 273 284 295 300 301 305 ] These various studies demonstrate a median PFS-6 rate that varied from 25% to 42.6%, median OS from 6.5 to 9.2 months, and radiological response rates from 29% to 42% in the BEV alone groups. In the BEV-combined arms, the PFS-6 rates varied from 19% to 50%, median OS from 6 to 10.2 months, and radiological response rates from 20% to 57%.…”

Section: Glioblastomamentioning

confidence: 94%

“…Other schedules of BEV have been evaluated in small cohorts of patients with recurrent GB. [ 140 235 ] A total of 61 patients with recurrent GB received 15 mg/kg/q3W of BEV in the study by Raizer. The PFS-6 was 25%, the median time to progression was 10.8 weeks, and the median OS was 25.6 weeks.…”

Section: Glioblastomamentioning

confidence: 99%

The future of high-grade glioma: Where we are and where are we going

Rhun¹,

Taillibert²,

Chamberlain³

2015

Surg Neurol Int

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High-grade glioma (HGG) are optimally treated with maximum safe surgery, followed by radiotherapy (RT) and/or systemic chemotherapy (CT). Recently, the treatment of newly diagnosed anaplastic glioma (AG) has changed, particularly in patients with 1p19q codeleted tumors. Results of trials currenlty ongoing are likely to determine the best standard of care for patients with noncodeleted AG tumors. Trials in AG illustrate the importance of molecular characterization, which are germane to both prognosis and treatment. In contrast, efforts to improve the current standard of care of newly diagnosed glioblastoma (GB) with, for example, the addition of bevacizumab (BEV), have been largely disappointing and furthermore molecular characterization has not changed therapy except in elderly patients. Novel approaches, such as vaccine-based immunotherapy, for newly diagnosed GB are currently being pursued in multiple clinical trials. Recurrent disease, an event inevitable in nearly all patients with HGG, continues to be a challenge. Both recurrent GB and AG are managed in similar manner and when feasible re-resection is often suggested notwithstanding limited data to suggest benefit from repeat surgery. Occassional patients may be candidates for re-irradiation but again there is a paucity of data to commend this therapy and only a minority of selected patients are eligible for this approach. Consequently systemic therapy continues to be the most often utilized treatment in recurrent HGG. Choice of therapy, however, varies and revolves around re-challenge with temozolomide (TMZ), use of a nitrosourea (most often lomustine; CCNU) or BEV, the most frequently used angiogenic inhibitor. Nevertheless, no clear standard recommendation regarding the prefered agent or combination of agents is avaliable. Prognosis after progression of a HGG remains poor, with an unmet need to improve therapy.

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“…The efficacy of BV monotherapy was demonstrated when patients in the RT + TMZ group experienced a recurrence. 6 , 20 – 26 Before the BV era, PFS, the 6-month PFS rate, OS, and 1-year OS in patients with recurrent glioblastoma were reported as ~2–3 months, 9%–28%, ~6 months, and 14%–32%, respectively. 25 PFS, 6-month PFS rate, and OS after BV therapy in patients with recurrent glioblastoma were reported as 2–4 months, 20%–50%, and 7–12 months, respectively.…”

Section: Bevacizumab For Recurrent Glioblastomamentioning

confidence: 99%

Bevacizumab for glioblastoma

Narita¹

2015

TCRM

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Individuals with glioblastoma are often characterized by older age, advanced neurologic manifestations at the primary stage, and unresectable tumors, and these factors are associated with poor treatment outcomes. Administration of bevacizumab (BV, Avastin®) promotes tumor regression and improves cerebral edema, and is expected to improve neurologic findings in many patients with malignant gliomas, including glioblastoma. Although the addition of BV to the conventional standard therapy (chemoradiotherapy with temozolomide) for newly diagnosed glioblastoma prolonged the progression-free survival time and the performance status of patients, it failed to extend overall survival time. However, more than 50% of glioblastoma patients show Karnofsky performance status ≤70 at initial presentation; therefore, BV should be used to improve or maintain their performance status as an initial treatment. Most of the adverse events of BV, except hypertension and proteinuria, occur as complications of glioblastoma, and explanation of the advantages and disadvantages of BV administration to patients is important. Herein, the efficacy, safety, and challenges of using BV for treating glioblastoma were reviewed.

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Bevacizumab Alone at 5 mg/kg in an Every-3-Week Schedule for Patients with Recurrent Glioblastomas: A Single Center Experience

Cited by 13 publications

References 13 publications

A randomized phase II trial of standard dose bevacizumab versus low dose bevacizumab plus lomustine (CCNU) in adults with recurrent glioblastoma

A randomized phase II trial of standard dose bevacizumab versus low dose bevacizumab plus lomustine (CCNU) in adults with recurrent glioblastoma

The future of high-grade glioma: Where we are and where are we going

Bevacizumab for glioblastoma

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