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

 karen 

California

 Laurl at ONS 

To get the ball rolling, do you have any specific questions, or would like some general information first? (this is Paula talking now!)

 karen 

I'm hoping to learn, no questions yet

 Laurl at ONS 

Okay, then here's some general info to start.

 Laurl at ONS 

Angiogenesis is an essential process for normal functions including wound healing, tissue repair, reproduction, and growth and development.

 Laurl at ONS 

Normally, angiogenesis is regulated...

 Laurl at ONS 

...by a delicate balance of stimulators and inhibitors.

 Laurl at ONS 

In tumor angiogenesis however...

 Laurl at ONS 

...that balance shifts leading to a cascade of irregular molecular and cellular events.

 Laurl at ONS 

Normal adult vasculature usually lays dormant (is already developed in the body) with long times between producing new capillaries.

 Laurl at ONS 

The difference between normal angiogenesis and tumor angiogenesis is that tumors the capillaries are tortuous and leaky.

 Laurl at ONS 

This allows tumor cells to migrate to distant sites.

 Laurl at ONS 

Anti- angiogenic agents that are FDA approved include Avastin, Thalidomide, and Revlimid.

 Laurl at ONS 

These essentially work to cut off the blood supply to the tumors. They are specific to those kinds of leaky capillaries, but they also do cause some side effects to normal vasculature.

 Laurl at ONS 

This includes arteriothrombic embolic events.

 Laurl at ONS 

Do you give any of these drugs in your setting?

 karen 

Yes, primarily Avastin. What is the explanation for a possible hypertensive reaction? And are there parameters for withholding Avastin?

 Laurl at ONS 

Great question. Yes, the hypertension reaction - reason for it I think is unknown.

 Laurl at ONS 

However, parameters for withholding: don't ever start therapy if pt has uncontrolled hypertension (or if they develop it during treatment). Other reasons to hold it is if they have had surgery for 28 days (impairs wound healing), and if they have a DVT or other embolic event.

 oncnurse 

Are there infusion reactions with Avastin?

 Laurl at ONS 

Infusion reactions - very rare...

 Laurl at ONS 

..in fact, one publication in JCO 2007 ( I think) stated that Avastin really doesn't have to be run any slower than over 30 minutes total, even with the first dose.

 Laurl at ONS 

This is in part because it is a humanized monoclonal antibody... as opposed to some of the other types ( like chimeric - like rituximab - which is part mouse/part human) or fully murine monoclonals ( all mouse).

 Laurl at ONS 

Let's talk about thalidomide and Revlimid - both have significant teratogenic potential ( not proved with Revlimid) ... and when taking either drug, patients must enroll in special programs that assure birth control is used, testing for pregnancy pre-treatment.

 Laurl at ONS 

Thalidomide has other different side effects than Avastin. It also can cause thromboembolic events.

 Laurl at ONS 

Hi Nedaz, welcome! Paula is here but having tech issues - I am writing her responses!

 Laurl at ONS 

Talking about thalidomide... also can cause somnolence, peripheral neuropathy, constipation and weight gain.

 Laurl at ONS 

Revlimid can cause peripheral edema, pruitis, constipation, and hematologic side effects.

 Laurl at ONS 

What kind of settings do you all work in - Nedaz, where are you from?

 karen 

infusion center assoc w/ hospital

 Laurl at ONS 

Where in California Karen (Paula lives in CA now!)

 nedaz 

I work at an out patient infusion area with the hospital, Before that I worked at a physician office.

 karen 

Irvine

 karen 

Oops, Orange, Ca...associated with UC Irvine

 Laurl at ONS 

So as infusion centers I suspect you are giving a good amount of Avastin....

 nedaz 

If a patient does not get a rash with Tarceva does that mean it is not working?

 nedaz 

How long have you seen Avastin given after chemo treatments? Ended?

 Laurl at ONS 

Tarceva is not an antiangiogenic agent...it targets epidermal growth factor receptor....this is a good point to make here.... anti-angiogenics on the other hand target VEGF- vascular endothelial growth factor ( particularly Avastin).

 Laurl at ONS 

But to get to the Tarceva question, there have been some studies that correlate rash associated positively with a response, but not enough evidence to declare definitively that no rash means no response.

 Laurl at ONS 

RE: Avastin after chemo: some caregivers continue to give Avastin even when the pt can no longer tolerate chemo...but this an individual provider/pt. profile decision.

 Laurl at ONS 

I've seen Avastin given for a year or two (these were glioblastoma pts) as long as there were getting staying stable and improved quality of life (this was on a clinical trial).

 karen 

But Tarceva does have angiogenesis inhibition action, right?

 Laurl at ONS 

Well, EGFR can also stimulate the VEGF receptor, it does has some antiangiogenic properties, but it's not marketed as an antiangiogenic - its marketed as a EGFR-inhibitor...seems like a fine line!

 Laurl at ONS 

There are a lot of growth factors that are stimulated in response to tumor angiogenesis. It can be confusing. In a matter of fact, there are multi-kinase inhibitors, such as sorafenib and sunitinib...that target multiple different pathways, including the VEGF inhibitor.

 karen 

So, as EGRF inhibitors inhibit endothelium, it is in fact also inhibiting vasculature...right?

 Laurl at ONS 

The "E" in EGFR actually stands for epidermal, not endothelial...however, EGFR inhibitors actually have been shown to have an effect on tumor angiogenesis.

 Laurl at ONS 

Tumor angiogenesis (i.e. tumor vasculature).

 Laurl at ONS 

You might want to also look on the Targeted Therapies chat transcripts (in previous chats on the ONS website) - there might be some more info there on Tarceva.

 Laurl at ONS 

What other questions might you have?

 karen 

Can these agents cure as single agents?

 Laurl at ONS 

Good question - currently mostly they are used in combination with traditional chemotherapies. Revlimid is given with dexamethasone in multiple myeloma. Thalidomide usually given in combo with chemo and dexamethasone. Avastin is given in combo generally with chemo. But if the chemotherapy treatment ends, some providers will continue to give the Avastin by itself as long as stable disease.

 Laurl at ONS 

Of course clinical trials are always underway... so who knows what will be possible in the future!

 Laurl at ONS 

And, these targeted therapies are beginning to be combined in clinical trials as well.

 Laurl at ONS 

Just want to be sure this gets into the transcript - It's about five minutes before our time is up - as you continue to ask questions, please don't 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 chat- we'd love to hear what you think of these chats! The URL is http://research.zarca.com/k/RsTUTRsSTQsXYTVVsPsP . You can do this after we are done (or later off the transcript).

 karen 

The convenience of some of these as oral agents is great. Thanks for the discussion. Bye

 Laurl at ONS 

Thank you for your participation! Please tells your coworkers about the next chat - Thursday at 3:30 pm Eastern!

 Laurl at ONS 

Thank you for attending - have a nice evening!