Toxicity and efficacy of lomustine and bevacizumab in recurrent glioblastoma patients

Jakobsen, Jan Nyrop; Urup, Thomas; Grunnet, Kirsten; Toft, Anders; Johansen, Maria Dinche; Poulsen, Sidsel Højklint; Christensen, Ib Jarle; Muhic, Aida; Poulsen, Hans Skovgaard

doi:10.1007/s11060-017-2736-x

Cited by 27 publications

(32 citation statements)

References 15 publications

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“…More details on administration has previously been described (40). After progression on primary therapy, 250 patients underwent reresection and 280 received bevacizumab in most cases given together with irinotecan or lomustine (CCNU) dependent on the local guidelines at the time (44). Selected patients further received different types of experimental treatment either before or after bevacizumab recurrence therapy.…”

Section: Treatmentmentioning

confidence: 99%

Clinical Characteristics of Gliosarcoma and Outcomes From Standardized Treatment Relative to Conventional Glioblastoma

et al. 2019

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Background: Gliosarcoma (GS) is a rare histopathologic variant of glioblastoma (GBM) characterized by a biphasic growth pattern consisting of both glial and sarcomatous components. Reports regarding its relative prognosis compared to conventional GBM are conflicting and although GS is treated as conventional GBM, supporting evidence is lacking. The aim of this study was to characterize demographic trends, clinical outcomes and prognostic variables of GS patients receiving standardized therapy and compare these to conventional GBM. Methods: Six hundred and eighty GBM patients, treated with maximal safe resection followed by radiotherapy with concomitant and adjuvant temozolomide at a single institution, were retrospectively reevaluated by reviewing histopathological records and tumor tissue for identification of GS patients. Clinico-pathological-and tumor growth characteristics were obtained via assessment of medical records and imaging analysis. Kaplan-Meier survival estimates were compared with log-rank testing, while Cox-regression modeling was tested for prognostic factors in GS patients. Results: The cohort included 26 primary gliosarcoma (PGS) patients (3.8%) and 7 secondary gliosarcoma (SGS) patients (1.0%). Compared to conventional GBM tumors, PGS tumors were significantly more often MGMT-unmethylated (73.9%) and located in the temporal lobe (57.7%). GS tumors often presented dural contact, while extracranial metastasis was only found in 1 patient. No significant differences were found between PGS and conventional GBM in progression-free-survival (6.8 and 7.6 months, respectively, p = 0.105) and in overall survival (13.4 and 15.7 months, respectively, p = 0.201). Survival following recurrence was not significantly different between PGS, SGS, and GBM. Temporal tumor location and MGMT status were found associated with PGS survival (p = 0.036 and p = 0.022, respectively). Conclusion: Despite histopathological and location difference between GS and GBM tumors, the patients present similar survival outcome from standardized treatment. These findings support continued practice of radiation and temozolomide for GS patients.

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Section: Treatmentmentioning

confidence: 99%

Clinical Characteristics of Gliosarcoma and Outcomes From Standardized Treatment Relative to Conventional Glioblastoma

et al. 2019

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“…Previously reported survival under BEV as a monotherapy or with concurrent chemotherapies (lomustine or irinotecan) is variable, with OS ranging from 4–12 months and PFS from 2.3–6 months [12,13,34,35,36,37]. The two single-arm phase II studies that enabled accelerated approval of BEV for recurrent GBM in 2009 reported survival under BEV monotherapy as 9.2 months OS and 4.2 months PFS [12], and 7.8 months OS and 4.0 months PFS, respectively [13].…”

Section: Discussionmentioning

confidence: 99%

Exploratory Study of the Effect of IMA950/Poly-ICLC Vaccination on Response to Bevacizumab in Relapsing High-Grade Glioma Patients

Boydell

Marinari

Migliorini

et al. 2019

Cancers

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Immunotherapy, including therapeutic vaccines, is increasingly being developed for patients with high-grade glioma, and combinations of immunotherapies and synergy with standard of care are being investigated. In this regard, bevacizumab (BEV) has been shown to synergize with immunotherapy in preclinical studies of glioma and in other tumour entities. Here, we conducted a post-hoc exploratory study to evaluate the effect of the IMA950/poly-ICLC peptide vaccine on subsequent BEV administration in high-grade glioma patients. 16 IMA950-vaccinated and 40 non-vaccinated patients were included. At initial diagnosis, patients benefited from surgery and chemoradiation. At first or subsequent recurrence, patients received 10mg/kg of BEV every 2–3 weeks. Primary endpoints were overall survival (OS) and progression-free survival (PFS) from BEV initiation. IMA950-vaccinated patients did not show improved response to BEV as compared to non-vaccinated patients: there was no difference in median PFS (2.6 vs. 4.2 months for vaccinated and control patients, respectively, p = 0.50) nor in median OS (7.8 vs. 10.0 months for vaccinated and control patients, respectively, p = 0.69). In conclusion, potential synergy of BEV and therapeutic vaccines, when administered sequentially, has yet to be established in the clinical setting of GBM recurrence. Potential synergy of concomitant administration should be tested in future trials.

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“…The common alkylating agents used in HGG are temozolomide (Tmz, 8-Carbamoyl-3-(2-chloroethyl)imidazo (5, 1-d)-l,2,3,5-tetrazin-4(3 H)-one) ( Figure 1 ) and lomustine (chloroethyl-cyclohexyl-nitrosourea, CCNU) [ 40 , 41 , 42 ]. Before Tmz, CCNU was the first-line of treatment in GBM patients (110 mg/m 2 orally every six weeks) [ 43 ].…”

Section: Overview Of Standard Therapy In Hggmentioning

confidence: 99%

Challenges and Perspectives of Standard Therapy and Drug Development in High-Grade Gliomas

et al. 2021

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Despite their low incidence rate globally, high-grade gliomas (HGG) remain a fatal primary brain tumor. The recommended therapy often is incapable of resecting the tumor entirely and exclusively targeting the tumor leads to tumor recurrence and dismal prognosis. Additionally, many HGG patients are not well suited for standard therapy and instead, subjected to a palliative approach. HGG tumors are highly infiltrative and the complex tumor microenvironment as well as high tumor heterogeneity often poses the main challenges towards the standard treatment. Therefore, a one-fit-approach may not be suitable for HGG management. Thus, a multimodal approach of standard therapy with immunotherapy, nanomedicine, repurposing of older drugs, use of phytochemicals, and precision medicine may be more advantageous than a single treatment model. This multimodal approach considers the environmental and genetic factors which could affect the patient’s response to therapy, thus improving their outcome. This review discusses the current views and advances in potential HGG therapeutic approaches and, aims to bridge the existing knowledge gap that will assist in overcoming challenges in HGG.

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Toxicity and efficacy of lomustine and bevacizumab in recurrent glioblastoma patients

Cited by 27 publications

References 15 publications

Clinical Characteristics of Gliosarcoma and Outcomes From Standardized Treatment Relative to Conventional Glioblastoma

Clinical Characteristics of Gliosarcoma and Outcomes From Standardized Treatment Relative to Conventional Glioblastoma

Exploratory Study of the Effect of IMA950/Poly-ICLC Vaccination on Response to Bevacizumab in Relapsing High-Grade Glioma Patients

Challenges and Perspectives of Standard Therapy and Drug Development in High-Grade Gliomas

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