Cure Alveolar Soft Part Sarcoma International (iCureASPS)

Neuro Oncol. 2008 Aug; 10(4): 624–630.
doi: 10.1215/15228517-2008-010
PMCID: PMC2666237
What is the risk of intracranial bleeding during anti-VEGF therapy?
Craig P. Carden, James M.G. Larkin, and Mark A. Rosenthal
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Abstract
Vascular endothelial growth factor (VEGF) is a key mediator of physiological and pathological angiogenesis. All solid tumors are dependent on pathological angiogenesis, and anti-VEGF therapy has demonstrated clinical benefit in breast, colorectal, non-small-cell lung, and renal carcinomas. Central nervous system metastases are common in many of these tumor types. An increased risk of bleeding has been reported with anti-VEGF therapy, but the risk of intracranial bleeding is unknown with this type of therapy. We reviewed the available data to investigate the risk of intracranial bleeding with anti-VEGF therapy in the presence and absence of CNS metastases. The PubMed and Medline databases and the Proceedings of the American Society of Clinical Oncology (ASCO) annual meetings were searched for articles, abstracts, and presentations of clinical trials. We identified 57 trials examining the safety and efficacy of anti-VEGF therapy in a total of 10,598 patients. Four trials examined the use of anti-VEGF therapy in treating patients with brain metastases. The presence of CNS metastases was a stated exclusion criterion in 76% of trials. The rate of intracranial bleeding was negligible. We conclude that there is no trial evidence that anti-VEGF therapy confers an increased risk of intracranial bleeding, even in the presence of CNS metastases. Future trials of anti-VEGF therapy should not exclude patients with controlled CNS metastases at enrollment.

Keywords: anti-VEGF therapy, bleeding, cancer, central nervous system, metastases

See Olga's post below..

Our review supports the inclusion of patients with brain metastases and high-grade gliomas in anti-VEGF therapy trials. Clinicians should carefully discuss the risk-benefit ratio in such situations, recognizing there may still be some doubts about the safety because of the small numbers of patients with known brain metastases and gliomas treated with such agents.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2666237/

I personally knew a sarcoma patient (not ASPS, we've met at Dr.Rolle's hospital in Coswing in Germany) who died from the sudden intracranial bleeding while on the TKI trial. He didn't know that he had a brain met - it appeared after he was screened for the trial and grew rapidly. One of the nicest people I've met.

Thanks Olga
I am so sorry to hear
As a result of your statement I added to my first post

Thank you for the interesting shared study information Debbie, and for your very important shared conflicting anecdotal information Olga. I personally remain skeptical about the findings of the study that you shared Debbie based on Olga's friend's very tragic TKI related intracranial bleeding death, as well as that of ASPS patient Paul Mavers who was being treated with Cediranib and, based on the albeit limited information that we received from one of Paul's friends, devastatingly died of a cerebral hemorrhage during brain surgery. Therefore, until further significant documented updated data regarding this concerning issue is available (the study abstract that you shared was published in 2008) and substantiated by anecdotal patient experiences and outcomes, I personally think that it is best to err on the side of caution and to abstain from TKI use if there are any untreated brain mets present, and until they have been successfully resected or treated and resolved.
With special concern, caring thoughts, and continued Hope,
bonni

I agree Bonni - and given the high rate of success of treatment - i.e. complete resolution of the brain mets after the timely radiosurgical treatment in many ASPS patients (GammaKnife preferably as they have more experience) or the resection of the easy located mets - there is no point in leaving the brain mets untreated and to allow them to appear and exist unknown and put a patient at risk for this fatal event.