Valganciclovir as Add-on to Standard Therapy in Glioblastoma Patients

Stragliotto, Giuseppe; Pantalone, Mattia Russel; Rahbar, Afsar; Bártek, Jiří; Söderberg‐Nauclér, Cecilia

doi:10.1158/1078-0432.ccr-20-0369

Cited by 35 publications

(43 citation statements)

References 43 publications

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“…While awaiting a possibility to find financial support for a randomized trial, the number of valganciclovir-treated patients increased to 139 patients by 2019. Among these, 102 had primary glioblastoma, and the median OS rate was very similar to that in the first trial: 24.1, versus 13.3 months in 231 contemporary control patients ( p < 0.0001) [ 14 ]. Both patients with methylated MGMT and those with an unmethylated MGMT promoter showed potential benefit from valganciclovir treatment.…”

Section: Discussionmentioning

confidence: 98%

“…Since 2006, we have treated 139 patients with glioblastoma with valganciclovir as an add-on to standard therapy; this drug treatment aims to target the negative effects of CMV in glioblastoma, an infection that is present in the majority of these tumors. We recently reported a retrospective data analysis demonstrating enhanced survival among 102 patients with primary glioblastoma who received valganciclovir as an add-on to standard therapy compared with 231 control patients [ 14 ]. Here, we also report that eight patients with secondary glioblastoma who were treated with valganciclovir as an add-on to second-line therapy survived significantly longer than controls after their progression to glioblastoma.…”

Section: Discussionmentioning

confidence: 99%

“…CMV may, therefore, represent a target of therapy in glioblastoma. In support of this statement, we recently reported that 102 patients with newly diagnosed primary glioblastoma treated with the anti-viral drug valganciclovir had a significantly improved OS as compared with 231 contemporary control patients with similar characteristics who were treated at the same institution (24.1 vs. 13.3 months, p < 0.0001) [ 14 ]. Thus, this virus could represent a treatment target in glioblastoma patients.…”

Section: Introductionmentioning

confidence: 95%

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Valganciclovir as Add-On to Standard Therapy in Secondary Glioblastoma

et al. 2020

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Patients with glioblastoma have a very poor prognosis despite aggressive therapeutic strategies. Cytomegalovirus has been detected in >90% of glioblastoma tumors. This virus can affect tumor progression and may represent a novel glioblastoma therapy target. We report, here, a retrospective survival analysis of patients with secondary glioblastoma who were treated with the anti-viral drug valganciclovir at Karolinska University Hospital in Stockholm. We performed survival analyses of eight patients with secondary glioblastoma who were treated with a standard dose of valganciclovir as an add-on to second-line therapy after their disease progression to glioblastoma. Thirty-six patients with secondary glioblastoma admitted during the same time period who received similar treatment and care served as contemporary controls. The patients treated with valganciclovir showed an increased median overall survival after progression to glioblastoma compared with controls (19.1 versus 12.7 months, p = 0.0072). This result indicates a potential positive effect of valganciclovir in secondary glioblastoma, which is in agreement with our previous observation that valganciclovir treatment improves the outcomes of patients with newly diagnosed glioblastoma. Larger randomized studies are warranted to prove this hypothesis.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

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Valganciclovir as Add-On to Standard Therapy in Secondary Glioblastoma

et al. 2020

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“…Considering the wide presence of HCMV in different tumor types, this virus may represent a potential target of therapy for HCMV positive malignancies, including breast cancer. Retrospective clinical trials have shown that antiviral therapy with valganciclovir as an add on to standard therapy seems to improve survival in patients with glioblastoma [ 44 , 45 ], and also dendritic cells vaccination shows promising results in these patients [ 46 ].…”

Section: Introductionmentioning

confidence: 99%

Detection of Human Cytomegalovirus Proteins in Paraffin-Embedded Breast Cancer Tissue Specimens—A Novel, Automated Immunohistochemical Staining Protocol

et al. 2021

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Emerging evidence supports a significant association between human cytomegalovirus (HCMV) and human malignancies, suggesting HCMV as a human oncomodulatory virus. HCMV gene products are found in >90% of breast cancer tumors and seem to be correlated with more aggressive disease. The definitive diagnosis of HCMV relies on identification of virus inclusions and/or viral proteins by different techniques including immunohistochemical staining. In order to reduce biases and improve clinical value of HCMV diagnostics in oncological pathology, automation of the procedure is needed and this was the purpose of this study. Tumor specimens from 115 patients treated for primary breast cancer at Akershus University Hospital in Norway were available for the validation of the staining method in this retrospective study. We demonstrate that our method is highly sensitive and delivers excellent reproducibility for staining of HCMV late antigen (LA), which makes this method useful for future routine diagnostics and scientific applications.

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“…[6][7][8] Furthermore, antiviral treatment of glioblastoma patients has indicated a prolonged overall survival. 9 This virus is reactivated by inflammation and promotes inflammation to secure its own existence, and a link has been proposed between HCMV, inflammation and cancer.…”

Section: Introductionmentioning

confidence: 99%

Evidence of human cytomegalovirus infection and expression of 5‐lipoxygenase in borderline ovarian tumors

Rahbar

Pantalone

Religa

et al. 2020

Journal of Medical Virology

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Borderline ovarian tumors (BOTs) belong to a group of tumors that are distinctly different from ovarian carcinomas. There is an increased risk of BOTs in patients with pelvic inflammatory disease. Human cytomegalovirus (HCMV) has been detected in ovarian cancer tissue specimens. This virus favors the inflammatory milieu by inducing expression of the potent inflammatory factor 5‐lipoxygenase (5LO), which stimulates cellular viability, cellular proliferation and activates antiapoptotic signaling pathways. Here, we aimed to examine presence of HCMV and 5LO in BOTs. Expression levels of HCMV proteins (IE and pp65) and 5LO were examined in paraffin embedded BOT tissue sections by immunohistochemistry staining and HCMV immunoglobulin M and immunoglobulin G (IgG) levels were determined by serology in blood samples obtained from 15 patients with BOTs identified in a prospective study at Karolinska University Hospital. Extensive expression of HCMV‐IE, pp65, and 5LO were detected in 87%, 40%, and 90% of examined BOT tissue sections, respectively. HCMV–IgG prevalence and antibody levels were significantly higher in patients with BOT compared to age matched healthy women (83.3% vs. 65,6%, respectively, p = .01). Whether HCMV can induce inflammation and affect the pathogenesis of BOTs should therefore be further investigated.

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Valganciclovir as Add-on to Standard Therapy in Glioblastoma Patients

Cited by 35 publications

References 43 publications

Valganciclovir as Add-On to Standard Therapy in Secondary Glioblastoma

Valganciclovir as Add-On to Standard Therapy in Secondary Glioblastoma

Detection of Human Cytomegalovirus Proteins in Paraffin-Embedded Breast Cancer Tissue Specimens—A Novel, Automated Immunohistochemical Staining Protocol

Evidence of human cytomegalovirus infection and expression of 5‐lipoxygenase in borderline ovarian tumors

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