Angiogenesis

 Laurl at ONS 

Welcome to the ONS Hot Topic Chats! Today’s expert is Paula Muehlbauer, who will be talking with us about any and all questions you have regarding Angiogenesis. Paula is experiencing technical issues from her computer so I will be typing her answers for her -she and I are in telephone contact right now -so you can feel free to ask your questions. I’ll type for Paula. To get started, where are you from?

 oncnurse 

Massachusetts

 Laurl at ONS 

To get started, let's define tumor angiogenesis. Angiogenesis is the development of new vasculature from pre-existing vasculature.

 Laurl at ONS 

It's a normal process for various physiologic functions such as growth and development, fetal development, wound healing, and menses.

 Laurl at ONS 

But in tumors it is abnormal.

 Laurl at ONS 

In tumors, the vascular network that grows and surrounds tumors feeds them so they can grow. But this vasculature is abnormal too - the capillaries are leaky, the tubules are tortuous, the basement membrane is leaky (the membrane at the bottom) ...

 Laurl at ONS 

... so this abnormal vasculature allows tumor cells to migrate.

 Laurl at ONS 

There is a series of molecular and cellular components that can induce tumor angiogenesis which include VEGF, basic fibroblastin growth factor, and other growth factors.

 Laurl at ONS 

Hypoxia tends to induce tumor angiogenesis.

 Laurl at ONS 

Other triggers include oncogenes.

 Laurl at ONS 

Do you have any specific questions about tumor angiogenesis?

 oncnurse 

Do all tumors develop angiogenesis?

 Laurl at ONS 

No...

 Laurl at ONS 

...they have to have the ability to turn on the angiogenic "switch".

 Laurl at ONS 

When that switch is thrown then they develop vasculature; otherwise, they remain dormant.

 Laurl at ONS 

Once switch is on, this allows the tumor cells to release angiogenic factors, and convert the tumor cell from non-angiogenic, to an angiogenic inducer.

 Laurl at ONS 

Do you give an antiangiogenic meds? What is your setting?

 oncnurse 

Yes, Avastin , Revlimid

 Laurl at ONS 

Ok, Avastin is the one known true anti-angiogenic drug. Revlimid and thalidomide are classified as anti-angiogenic, but it's really not known how they work.

 Laurl at ONS 

Some of the EGFR inhibitors like Tarceva and Erbitux have anti-angiogenic properties as well.

 Laurl at ONS 

But they are not classified as anti-angiogenic agents.

 Laurl at ONS 

Any administration or side effects issues you've seen?

 Laurl at ONS 

Well.... with Avastin you often see hypertension, proteinuria usually associated with the hypertension, delayed wound healing....

 Laurl at ONS 

...and arterial and venous thrombotic events.

 Laurl at ONS 

Have you seen any of these in your patients?

 Laurl at ONS 

Hypertension should be well controlled before putting anyone on Avastin, and patients need to be 28 days post-surgery ( at least) before starting Avastin.

 Laurl at ONS 

So, with thalidomide...and Revlimid too - patients must be on a special program that verifies that they are not pregnant, and agree to reliable birth control before they can get their prescription filled each month. This is due to the teratogenic side effect profile of the drugs.

 Laurl at ONS 

Thalidomide also can cause sleepiness, constipation, peripheral neuropathy, and weight gain.

 Laurl at ONS 

Revlimid can cause myelosuppression, rash, and peripheral edema.

 Laurl at ONS 

Avastin is a humanized monoclonal so infusion reactions are rare, because of being primarily human (as opposed to those that are chimeric - part human/part mouse, or murine (all mouse).

 Laurl at ONS 

Any questions?

 Laurl at ONS 

Welcome!

 Laurl at ONS 

Paula is here, but unfortunately is having technical issues. I'm from ONS and I’m typing her responses - she and I are on the phone -

 diane 

ok

 Laurl at ONS 

We've talked a little about what angiogenesis is...you can refer back to the transcript for those descriptions. Do you have any specific questions about the pathophysiology, the antiangiogenics, side effects?

 Laurl at ONS 

Do you have any good case studies that you'd like to share?

 Laurl at ONS 

Any pts that have experienced treatment reactions?

 Laurl at ONS 

In terms of how these drugs are given, they are pretty much given in combination with other agents (chemotherapy). Some providers will continue Avastin after chemo ends, but this is an individual decision of the provider.

 Laurl at ONS 

I’m happy to answer any questions!

 oncnurse 

Is there some pathophysiologic explanation you can give re: why people get DVTs while on these drugs?

 Laurl at ONS 

Most likely because these drugs do affect the normal vasculature as well as tumor vasculature.

 Laurl at ONS 

Endothelial cells are found in normal vasculature as well as tumor vasculature...

 Laurl at ONS 

...VEGF binds to the receptors on the surface of endothelial cells, both for normal vasculature and tumor vasculature. Avastin targets VEGF so it's not necessarily going to be specific for tumor vasculature only.

 Laurl at ONS 

We have about 3 or 4 minutes left - please, when we are done, forget to take a moment to cut and paste this URL into your browser and take our very brief survey at the end of the chats - we'd love to hear what you think of these chats! The URL is http://research.zarca.com/k/RsTUTRsSTQsXYTVVsPsP .. Cut and paste into your browser click and take the survey - thank you! You can also find this URL in the transcript of this chat which will be posted in the next day or so.

 Laurl at ONS 

Well, our time is up! I hope that you found this information helpful! Please tell your coworkers about the final chat in this series tomorrow at 11am Eastern time. Have a great day!

 oncnurse 

Thank you! Bye!