Antiangiogenic metronomic therapy for children with recurrent embryonal brain tumors

Peyrl, Andreas; Chocholous, Monika; Kieran, Mark W.; Azizi, Amedeo A.; Prucker, Christina; Czech, Thomas; Dieckmann, Karin; Schmook, Maria-Theresa; Haberler, Christine; Leiss, Ulrike; Slavc, Irene

doi:10.1002/pbc.24006

Cited by 114 publications

(104 citation statements)

References 36 publications

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“…Unconsciousness, paraparesis, and cauda equina syndrome have also been reported. Local intrathecal chemotherapy has been studied for pediatric patients with different brain tumors, including medulloblastoma [13][14][15][16][17] (Table 1), showing responses and good tolerability.…”

Section: Discussionmentioning

confidence: 99%

Treatment for recurrent medulloblastoma with intrathecal liposomal cytarabine and systemic metronomic combination therapy

Nygaard

Kivivuori²

2012

Anti-Cancer Drugs

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The prognosis of recurrent medulloblastoma is dismal, with a median survival of less than 1 year. Our patient was initially diagnosed with high-risk medulloblastoma when he was 14 years old. He had a recurrence 18 months after the end of therapy. Recurrence treatment consisted of 13 intrathecal applications of liposomal cytarabine over an 18-month period, and oral metronomic antiangiogenic therapy with thalidomide, celecoxib, and etoposide. Side effects from the intrathecal treatment were most likely related to arachnoiditis despite prolonged prophylaxis with steroids. He also developed partial hearing loss. Neutropenia was the main side effect of the metronomic therapy. He remains alive, with a good quality of life and without evidence of disease 34 months from the start of recurrence therapy. This combination of local antineoplastic and systemic antiangiogenic therapy seems to be promising for recurrent medulloblastoma. However, more patients and standardized protocols are needed to verify the benefit of this combination therapy and to define the correct duration of treatment.

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Section: Discussionmentioning

confidence: 99%

Treatment for recurrent medulloblastoma with intrathecal liposomal cytarabine and systemic metronomic combination therapy

Nygaard

Kivivuori²

2012

Anti-Cancer Drugs

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“…Promising results were recently reported for a metronomic chemotherapy protocol in the treatment of recurrent embryonal brain tumors (46). It took more than ten years to empirically and incrementally develop the sophisticated 8-drug combination regimen based on the results of previous pre-clinical and clinical studies (47–49).…”

Section: Discussionmentioning

confidence: 99%

Formalizing an Integrative, Multidisciplinary Cancer Therapy Discovery Workflow

McGuire¹,

Enderling

Wallace

et al. 2013

Cancer Research

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Although many clinicians and researchers work to understand cancer, there has been limited success to effectively combine forces and collaborate over time, distance, data and budget constraints. Here we present a workflow template for multidisciplinary cancer therapy that was developed during the 2nd Annual Workshop on Cancer Systems Biology sponsored by Tufts University, Boston, MA in July 2012. The template was applied to the development of a metronomic therapy backbone for neuroblastoma. Three primary groups were identified: clinicians, biologists, and scientists (mathematicians, computer scientists, physicists and engineers). The workflow described their integrative interactions; parallel or sequential processes; data sources and computational tools at different stages as well as the iterative nature of therapeutic development from clinical observations to in vitro, in vivo, and clinical trials. We found that theoreticians in dialog with experimentalists could develop calibrated and parameterized predictive models that inform and formalize sets of testable hypotheses, thus speeding up discovery and validation while reducing laboratory resources and costs. The developed template outlines an interdisciplinary collaboration workflow designed to systematically investigate the mechanistic underpinnings of a new therapy and validate that therapy to advance development and clinical acceptance.

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“…Regarding the use of metronomic dosing for PBT, he said that this therapy had demonstrated some encouraging results, using single agents such as topotecan [53] or etoposide, in multiple brain tumours, with response rate from 50 to 80%, and with multi-agent regimens such as bevacizumab, thalidomide, celecoxib, fenofibrate, etoposide and cyclophosphamide, COMBAT (temozolomide, etoposide, celecoxib, vitamin D, fenofibrate, retinoic acid), or thalidomide, celecoxib, low dose etoposide and cyclophosphamide, which have demonstrated some benefit in patients with relapsed PBT [54], or bevacizumab and irinotecan followed by metronomic maintenance with weekly vinblastine, in low-grade gliomas [55]. …”

Section: Session 2: Clinic Experience In Paediatric Cancermentioning

confidence: 99%

“…The compound is a selective agonist for the V2 vasopressin membrane receptor, mediating antidiuretic, and haemostatic responses in kidney-collecting ducts and endothelial cells, respectively [53]. The presence of vasopressin receptors has been also documented in various human malignancies, including breast, colorectal, and small-cell neuroendocrine cancer [54]. …”

Section: Session 3: Clinical Experience In Adult Cancermentioning

confidence: 99%

Highlights from the 1st Latin American meeting on metronomic chemotherapy and drug repositioning in oncology, 27–28 May, 2016, Rosario, Argentina

Rose¹,

André²,

Rozados³

et al. 2016

ecancer

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Following previous metronomic meetings in Marseille (2011), Milano (2014), and Mumbai (2016), the first Latin American metronomic meeting was held in the School of Medical Sciences, National University of Rosario, Rosario, Argentina on 27 and 28 of May, 2016. For the first time, clinicians and researchers with experience in the field of metronomics, coming from different countries in Latin America, had the opportunity of presenting and discussing their work. The talks were organised in three main sessions related to experience in the pre-clinical, and clinical (paediatric and adult) areas. The different presentations demonstrated that the fields of metronomic chemotherapy and repurposing drugs in oncology, known as metronomics, constitute a branch of cancer therapy in permanent evolution, which have strong groups working in LatinAmerica, both in the preclinical and the clinical settings including large, adequately designed randomised studies. It was shown that metronomics offers treatments, which, whether they are combined or not with the standard therapeutic approaches, are not only effective but also minimally toxic, with the consequent improvement of the patient’s quality of life, and inexpensive, a feature very important in low resource clinical settings. The potential use of metronomic chemotherapy was proposed as a cost/effective treatment in low-/middle-income countries, for adjuvant therapy in selected tumours. The fundamental role of the governmental agencies and non-governmental alliances, as the Metronomic Global Health Initiative, in supporting this research with public interest was underlined.

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Antiangiogenic metronomic therapy for children with recurrent embryonal brain tumors

Abstract: Our results suggest that the chosen antiangiogenic drug combination is particularly beneficial for patients with MB and warrants further investigation.

Cited by 114 publications

References 36 publications

Treatment for recurrent medulloblastoma with intrathecal liposomal cytarabine and systemic metronomic combination therapy

Treatment for recurrent medulloblastoma with intrathecal liposomal cytarabine and systemic metronomic combination therapy

Formalizing an Integrative, Multidisciplinary Cancer Therapy Discovery Workflow

Highlights from the 1st Latin American meeting on metronomic chemotherapy and drug repositioning in oncology, 27–28 May, 2016, Rosario, Argentina

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