Analysis of TKI Side Effects and Rebound - Still Looks OK

[Fictional]

I've been trying to keep up with this issue in the event our daughter might return to Sutent, or try Pazopanib or Cediranib.

I recently found a presentation of data discussing the controversy over whether anti-angiogenesis inhibitors could be increasing metastases, or causing more harm than good when they are removed. As some of you know, there has been mouse studies suggesting that TKIs could increase mets for instance to liver. Here's the link: http://www.eticho.org/Files/Doc/Angioge ... idence.pdf

The latest large-scale analysis of Avastin (one of the earliest anti-angiogenesis agents), doesn't support a deleterious effect. In other words, it is not better if nothing had been tried. The concern was that if coming off the drug induces rebound, is the net result worse than if the medication had never been started. The conclusion was "No, it was not worse than if medication hadn't been tried".

I did find it somewhat alarming though to see how fast tumor blood vessels returned after only a few weeks off TKIs. When our dd was on Sutent before her surgery she had to have 3 weeks off before surgery (apparently there was still some oozing acc to the surgeon) and 3 weeks post-op before resuming another drug. We did see a slight rebound in the lung mets growth, but that has also been reported by just removing a large primary tumor.

I guess I still think there was a net benefit to adjuvant Sutent beforehand...but I'm glad we suggested continuing on daily dosing (she had been on the on/off cycle) to minimize the off time before surgery. The surgeon was worried about the tumors vascularity before the surgery (Boston recommended embolizing the tumor, which we worried could be worse for inducing metastases), but it came out just fine without embolization.

[Bonni Hess]

Thank you for sharing this very important information 'F'. I feel that it is certainly something that anyone considering treatment with anti-angiogenic TKI drugs should read and discuss with their oncologist. It seems that there are still no definitive answers or long term comprehensive results regarding the issue of TKI developed resistance and rebound in human beings, and that only time and experience will provide a better understanding of the risks of reduced overall survival versus the benefit of progression free survival with these promising, but still quite experimental new drugs.
With special caring thoughts and continued Hope,
Bonni