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Table of Contents
LETTER TO EDITOR
Year : 2021  |  Volume : 4  |  Issue : 3  |  Page : 576-577

Bevacizumab in recurrent glioma: Variable doses, volatile benefits


Department of Medical Oncology, Neuro-Oncology Cancer Management Team, Apollo Proton Cancer Centre, Chennai, Tamil Nadu, India

Date of Submission23-Jul-2021
Date of Decision01-Aug-2021
Date of Acceptance07-Aug-2021
Date of Web Publication10-Sep-2021

Correspondence Address:
Sujith Kumar Mullapally
Department of Medical Oncology, Neuro-Oncology Cancer Management Team, Apollo Proton Cancer Centre, 4/661, Dr. Vikram Sarabai Instronic Estate 7th Street, Dr. Vasi Estate, Phase II, Tharamani, Chennai - 600 041, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/crst.crst_172_21

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How to cite this article:
Mullapally SK, Panda PK. Bevacizumab in recurrent glioma: Variable doses, volatile benefits. Cancer Res Stat Treat 2021;4:576-7

How to cite this URL:
Mullapally SK, Panda PK. Bevacizumab in recurrent glioma: Variable doses, volatile benefits. Cancer Res Stat Treat [serial online] 2021 [cited 2021 Dec 4];4:576-7. Available from: https://www.crstonline.com/text.asp?2021/4/3/576/325901



It was with great interest that we read the article by D'Souza et al.[1] on the use of low-dose bevacizumab in recurrent glioma[1] and the accompanying editorial by Dr. Biswas.[2] The authors must be congratulated for this interesting and pertinent study done in the context of recurrent glioma with no definite treatment options when re-surgery or re-irradiation is not feasible. The recently concluded American Society of Clinical Oncology annual meeting 2021 included a few studies in recurrent glioma in which the therapy was based on the presence of driver mutations such as BRAF and NTRK, but these cases constitute only a minority of the clinical burden we see in neuro-oncology practice.

Bevacizumab, although approved, is yet to be established as an effective agent for widespread use in recurrent glioma. The current use is based on the studies by Taal et al.[3] and Vredenburgh et al.,[4] which had shown symptomatic relief and improved progression-free survival (PFS). These studies done in combination with chemotherapy such as irinotecan and lomustine failed to change the practice primarily because of the low magnitude of benefit and high toxicity rates. Treatment-related toxicities such as hypertension and bleeding have been attributed to bevacizumab. Whether low-dose bevacizumab would have resulted in lesser toxicities with similar benefits is an open question.

The majority of patients with recurrent glioma have residual neurological deficits affecting their performance status and quality of life in terms of increased dependence in their activities of daily living and lack of social engagements. For any drug to be accepted as a standard of care, significant and meaningful improvement in overall survival with an acceptable or minimal toxicity profile is desirable. Financial toxicity also should be considered as an important factor in such scenarios as many of these patients tend to be in the young or middle-age groups, whereby their social and economic independence is severely compromised.[5],[6],[7] It is in this context that the current study assumes importance for clinical practice in patients with recurrent glioma.

In spite of the dose used, the main concern is the short PFS duration (3–4 months). Often, patients experience improvement in their symptoms and imaging studies show a reduction in the tumor edema/fluid-attenuated inversion recovery changes; however, during subsequent visits, clinical and radiological progression secondary to bevacizumab resistance is usually noted.[8] This “volatile” response of bevacizumab has prevented its routine adoption in clinical practice.

The study by D'Souza et al. has attempted to provide preliminary answers to the conundrum of the optimal dosing of bevacizumab.[2] Future randomized studies comparing low and high doses of bevacizumab may not be of relevance if they do not incorporate the appropriate study arms including the combination of bevacizumab with drugs which might help in sustaining the response achieved with bevacizumab. Future studies could possibly include three arms with low dose and high dose of bevacizumab each in combination with the trial drug and the control arm with high dose bevacizumab alone. The trial drug can be a repurposed drug as used in metronomic chemotherapy or newer molecules such as immunotherapy. Multi-institutional collaborative trials could provide the required impetus to solve this intriguing clinical dilemma.[9]

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
D'Souza H, Singh GK, Menon N, Abhyankar A, Puranik A, Mahajan A, et al. Optimal dose of bevacizumab in recurrent glioma: A retrospective study. Cancer Res Stat Treat 2021;4:224-30.  Back to cited text no. 1
    
2.
Biswas A. Bevacizumab in progressive or recurrent glioblastoma: A quest for the optimal dosage. Cancer Res Stat Treat 2021;4:56-9.  Back to cited text no. 2
    
3.
Taal W, Oosterkamp HM, Walenkamp AM, Dubbink HJ, Beerepoot LV, Hanse MC, et al. Single-agent bevacizumab or lomustine versus a combination of bevacizumab plus lomustine in patients with recurrent glioblastoma (BELOB trial): A randomised controlled phase 2 trial. Lancet Oncol 2014;15:943-53.  Back to cited text no. 3
    
4.
Vredenburgh JJ, Desjardins A, Herndon JE 2nd, Marcello J, Reardon DA, Quinn JA, et al. Bevacizumab plus irinotecan in recurrent glioblastoma multiforme. J Clin Oncol 2007;25:4722-9.  Back to cited text no. 4
    
5.
Kalra D, Menon N, Singh GK, Dale O, Adak S, Das S, et al. Financial toxicities in patients receiving systemic therapy for brain tumors: A cross-sectional study. Cancer Res Stat Treat 2020;3:724-9.  Back to cited text no. 5
  [Full text]  
6.
Gupta A, Gyawali B. Digging deeper into cancer-associated financial toxicity in low and middle-income countries. Cancer Res Stat Treat 2021;4:172-3.  Back to cited text no. 6
  [Full text]  
7.
Jha V, Dinesh TA, Nair P. Cancer – Too costly to cure? Cancer Res Stat Treat 2021;4:173-4.  Back to cited text no. 7
  [Full text]  
8.
Tamura R, Tanaka T, Miyake K, Yoshida K, Sasaki H. Bevacizumab for malignant gliomas: Current indications, mechanisms of action and resistance, and markers of response. Brain Tumor Pathol 2017;34:62-77.  Back to cited text no. 8
    
9.
Noronha V. Making a case for cancer research in India. Cancer Res Stat Treat 2018;1:171-4.  Back to cited text no. 9
    




 

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