# Bevacizumab alternating chemotherapy for improving the survival of patients with recurrent high-grade glioma

**Authors:** Ping-Chuan Liu, Chao-Yang Kuo, Yi-Wei Chen, Chun-Fu Lin, Shih-Chieh Lin, Feng-Chi Chang, Ming-The Chen, Jau-Ching Wu, Yi-Yen Lee

PMC · DOI: 10.1093/noajnl/vdaf157 · Neuro-Oncology Advances · 2025-07-18

## TL;DR

A treatment combining bevacizumab with alternating chemotherapy improved survival in patients with recurrent high-grade gliomas, especially for grade 4 tumors.

## Contribution

The study introduces a bevacizumab alternating chemotherapy regimen that significantly improves survival outcomes in recurrent high-grade glioma patients.

## Key findings

- The BAC regimen improved median OS to 29 months versus 19 months with BEV alone in grade 4 gliomas.
- Patients with MGMT-methylated grade 4 gliomas on BAC had the longest median OS of 33 months.
- BAC was well tolerated and showed better postrecurrence survival in younger patients.

## Abstract

High-grade glioma (HGG) is an aggressive tumor for which there are no effective therapies at recurrence, especially for isocitrate dehydrogenase (IDH)-wild-type glioblastoma. This retrospective study compared survival outcomes between patients receiving bevacizumab alternating chemotherapy (BAC) and those receiving bevacizumab (BEV) alone.

We collected data from 95 adult patients with rHGG who were treated at our institute between January 2018 and August 2023. The patients were divided into 3 groups based on treatment and glioma grade: BAC regimen to treat grade 3 gliomas (n = 23), BAC regimen to treat grade 4 gliomas (n = 29), and treatment with BEV alone (n = 43). The BAC regimen included 2 cycles of etoposide + carboplatin, followed by 1 cycle of cyclophosphamide + vinblastine, with bevacizumab (10 mg/kg) every 4 weeks. One full cycle lasted approximately 3 months. We analyzed overall survival (OS) and postrecurrence survival (PRS).

In patients with grade 4 gliomas, the BAC regimen significantly improved survival compared with BEV alone, with a median OS of 29 versus 19 months and a PRS of 16 versus 10 months (both P < .05). In the IDH-wild-type subgroup, the BAC regimen produced a median OS of 27 versus 19 months and a PRS of 16 versus 10 months (P < .05). The 2-year OS and PRS rates were also higher in the BAC groups. Notably, patients with MGMT-methylated grade 4 gliomas treated with the BAC regimen had the longest median OS, 33 months.

The BAC regimen appears effective and well tolerated in adult patients with rHGG, particularly in younger patients. Its alternating design may improve the median OS (29 vs. 19 months) and PRS (16 vs. 10 months) of patients with grade 4 gliomas while maintaining safety. As a practical option for those ineligible for clinical trials, BAC warrants further evaluation in prospective randomized studies to confirm its benefits and address the limitations of retrospective analysis.

## Linked entities

- **Genes:** IDH1 (isocitrate dehydrogenase (NADP(+)) 1) [NCBI Gene 3417], MGMT (O-6-methylguanine-DNA methyltransferase) [NCBI Gene 4255]
- **Chemicals:** etoposide (PubChem CID 36462), carboplatin (PubChem CID 426756), cyclophosphamide (PubChem CID 2907), vinblastine (PubChem CID 13342)
- **Diseases:** high-grade glioma (MONDO:0100342), glioblastoma (MONDO:0018177)

## Full-text entities

- **Genes:** MGMT (O-6-methylguanine-DNA methyltransferase) [NCBI Gene 4255], PGR (progesterone receptor) [NCBI Gene 5241] {aka NR3C3, PR}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, IDH1 (isocitrate dehydrogenase (NADP(+)) 1) [NCBI Gene 3417] {aka HEL-216, HEL-S-26, IDCD, IDH, IDP, IDPC}
- **Diseases:** SCLC (MESH:D055752), death (MESH:D003643), pneumonia (MESH:D011014), HGG (MESH:D008228), necrosis (MESH:D009336), anemia (MESH:D000740), ototoxicity (MESH:D006311), hypokalemia (MESH:D007008), Gliomas (MESH:D005910), fever (MESH:D005334), hypernatremia (MESH:D006955), neurological deficits (MESH:D009461), thrombocytopenia (MESH:D013921), pancytopenia (MESH:D010198), liver enzyme impairment (MESH:D017093), Infections (MESH:D007239), cancers (MESH:D009369), oral mucositis (MESH:D013280), hyponatremia (MESH:D007010), urinary tract infections (MESH:D014552), deep vein thrombosis (MESH:D020246), gastrointestinal perforation (MESH:D005767), electrolyte (MESH:D014883), hypertension (MESH:D006973), GBM (MESH:D005909), anaplastic oligodendrogliomas (MESH:D009837), primary (MESH:D010538), fatigue (MESH:D005221), pulmonary embolus (MESH:D004617), renal function impairment (MESH:D007674), breast cancer (MESH:D001943), gastrointestinal problems (MESH:D012817), cytotoxic (MESH:D064420), nausea/vomiting (MESH:D020250), BAC (MESH:C536589), anaplastic astrocytoma (MESH:D001254), neutropenia (MESH:D009503)
- **Chemicals:** cisplatin (MESH:D002945), O6-methylguanine (MESH:C008449), temozolomide (MESH:D000077204), nitrosourea (MESH:D009607), VBL (MESH:D014747), vorinostat (MESH:D000077337), CB (MESH:D016190), methadone (MESH:D008691), vincristine (MESH:D014750), ETP (MESH:D005047), procarbazine (MESH:D011344), disulfiram (MESH:D004221), irinotecan (MESH:D000077146), dasatinib (MESH:D000069439), CP (MESH:D003520), BAC (-), BEV (MESH:D000068258), CCNU (MESH:D008130), metformin (MESH:D008687)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12311935/full.md

## References

43 references — full list in the complete paper: https://tomesphere.com/paper/PMC12311935/full.md

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Source: https://tomesphere.com/paper/PMC12311935