Cilengitide treatment of newly diagnosed glioblastoma patients does not alter patterns of progression

  title={Cilengitide treatment of newly diagnosed glioblastoma patients does not alter patterns of progression},
  author={Günter Eisele and Antje Wick and A. Eisele and Paul M J Clement and J{\"o}rg-Christian Tonn and Ghazaleh Tabatabai and Adrian F. Ochsenbein and Uwe Schlegel and Bart Neyns and Dietmar Krex and Matthias Simon and Guido Nikkhah and Martin Picard and Roger Stupp and Wolfgang Wick and Michael Weller},
  journal={Journal of Neuro-Oncology},
The integrin antagonist cilengitide has been explored as an adjunct with anti-angiogenic properties to standard of care temozolomide chemoradiotherapy (TMZ/RT → TMZ) in newly diagnosed glioblastoma. Preclinical data as well as anecdotal clinical observations indicate that anti-angiogenic treatment may result in altered patterns of tumor progression. Using a standardized approach, we analyzed patterns of progression on MRI in 21 patients enrolled onto a phase 2 trial of cilengitide added to TMZ… 

Therapeutic approaches to overcome temozolomide resistance in glioblastoma

Experimental study of selective MGMT peptides mimicking TMZ drug resistance in glioma

A Systematic Review of Glioblastoma-Targeted Therapies in Phases II, III, IV Clinical Trials

A very detailed and exhaustive approach the literature of these last 20 years on glioblastoma targeted therapies in Phases II-IV of 257 clinical trials on adults with newly diagnosed or recurrent GBMs (excluding targeted immunotherapies and therapies targeting tumor cell metabolism, well documented in recent reviews).

Prodding the Beast: Assessing the Impact of Treatment-Induced Metastasis.

This review will focus on the preclinical model systems used to evaluate TIM and explore the mechanisms that influence overall treatment efficacy and provide rationales for future drug combination approaches with antimetastatic agents to improve outcomes and reduce resistance.

A comparative assessment of the effects of integrin inhibitor cilengitide on primary culture of head and neck squamous cell carcinoma (HNSCC) and HNSCC cell lines

Cilengitide has significantly inhibited the proliferation of HNSCC cells in a dose-dependent way and RGD-containing small-molecule synthetic peptides might be considered in tumor chemotherapy in the near future.

Recent advances in targeted therapy for glioblastoma

This review provides up-to-date information on the drugs and their molecular targets, which are currently in different stages of clinical trials and would provide better therapy in the future.

For the next trick: new discoveries in radiobiology applied to glioblastoma.

  • J. DebusA. Abdollahi
  • Medicine
    American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting
  • 2014
It becomes increasingly apparent that treatment of GBM needs to integrate therapies targeting all distinct pathophysiological features, and recent approaches in GBM therapy include inhibition of invasion, antiangiogenesis and stroma modulators, and activation of immune response.

Glioma targeted therapy: insight into future of molecular approaches

Novel feasible or potential targets for treatment of gliomas, especially IDH-wild type glioblastoma are discussed, especially the p53 and retinoblastum pathway and epidermal growth factor receptor (EGFR) gene alteration.

Development of targeted therapies in treatment of glioblastoma

An up-to-date review of the current targeted therapies in GBM is provided, which include drugs directed against specific targets which play essential roles in the proliferation, survival, and invasiveness of GBM cells.

The Role of Hypoxia and SRC Tyrosine Kinase in Glioblastoma Invasiveness and Radioresistance

The role of the hypoxic microenvironment and SRC proto-oncogene non-receptor tyrosine kinase in the activation of radioresistance and invasion pathways of glioblastoma is described, providing updated evidences on the involvement of SRC in these processes.



Phase I/IIa study of cilengitide and temozolomide with concomitant radiotherapy followed by cilengitide and temozolomide maintenance therapy in patients with newly diagnosed glioblastoma.

  • R. StuppM. Hegi M. Weller
  • Medicine, Biology
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 2010
Compared with historical controls, the addition of concomitant and adjuvant cilengitide to standard chemoradiotherapy demonstrated promising activity in patients with glioblastoma with MGMT promoter methylation.

Cilengitide combined with standard treatment for patients with newly diagnosed glioblastoma and methylated O6-methylguanine-DNA methyltransferase (MGMT) gene promoter: Key results of the multicenter, randomized, open-label, controlled, phase III CENTRIC study.

  • M. HegiT. Gorlia M. Weller
  • Medicine
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 2013
CIL failed to prolong PFS or OS in patients with newly diagnosed glioblastoma and methylated MGMT gene promoter and the previously reported safety profile of CIL in addition to standard therapy was confirmed.

A novel tool to analyze MRI recurrence patterns in glioblastoma.

Analysis of recurrence patterns revealed no difference between the groups in the size of the recurrent tumor or in the differential effect on the distance of the recurrences from the preoperative tumor location, and the data show the feasibility of groupwise recurrence pattern analysis.

Bevacizumab does not increase the risk of remote relapse in malignant glioma

The risk of distant or diffuse recurrence at the time of failure of BEV‐containing treatments was not higher than with anti‐VEGF–free regimens, arguing against a specific property of BEv that promotes distant tumor growth or a gliomatosislike phenotype at recurrence.

Tumor response based on adapted Macdonald criteria and assessment of pseudoprogression (PsPD) in the phase III AVAglio trial of bevacizumab (Bv) plus temozolomide (T) plus radiotherapy (RT) in newly diagnosed glioblastoma (GBM).

The AVAglio study adapted Macdonald criteria to address anti-angiogenic therapy/corticosteroid use by incorporating non-contrast-enhancing components and integrating a strict algorithm to standardize assessment of possible PsPD.

RTOG 0825: Phase III double-blind placebo-controlled trial evaluating bevacizumab (Bev) in patients (Pts) with newly diagnosed glioblastoma (GBM).

  • J. DignamM. Won M. Mehta
  • Medicine
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 2013
The addition of Bev for newly diagnosed GBM did not improve OS, did improve PFS but did not reach the significance criterion, and risk subset results suggested strongly against the upfront use of BeV in the best prognosis pts.

Invasion as limitation to anti-angiogenic glioma therapy.

Tumor cell invasion was tightly associated with preexistent blood vessels, suggesting that increased cooption of the host vasculature could represent a compensatory mechanism that is selected for by inhibiting adequate tumor vascularization.

Anti-VEGF treatment reduces blood supply and increases tumor cell invasion in glioblastoma

The present work underlines the need to combine anti-angiogenic treatment in GBMs with drugs targeting specific signaling or metabolic pathways linked to the glycolytic phenotype, and suggests that vascular remodeling induced by anti-VEGF treatment leads to a more hypoxic tumor microenvironment.

Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma.

The addition of temozolomide to radiotherapy for newly diagnosed glioblastoma resulted in a clinically meaningful and statistically significant survival benefit with minimal additional toxicity.