Targeted Therapies: Symptom Management

 Laurl at ONS 

Welcome to the ONS Hot Topic Chats! Today’s expert is Mary Pat Lynch, who will be talking with us about any and all questions you have regarding targeted therapies. Welcome Mary Pat!

 marypatlynch 

Welcome everyone. Where are you from?

 desphippsrn 

Louisville, KY

 Kellie 

Albert Lea, MN

 marypatlynch 

Well, good morning, you are both up early! I'm in Philadelphia and its a cold morning here!

 lkrioux 

Charlotte, NC which I understand is important when you consider IGE antibodies

 marypatlynch 

We're talking about targeted therapies, does anyone have any questions?

 marypatlynch 

Good point!

 marypatlynch 

You are referring to all the companies that make these drugs, which are in NC, right?

 marypatlynch 

Targeted therapies differ from traditional chemotherapies in that targeted therapies use drugs that that block the growth and spread of cancer.

 marypatlynch 

By focusing on molecular and cellular changes that are specific to the cancer, targeted therapies may be more effective than chemotherapy and less harmful to normal cells.

 desphippsrn 

I have a question about HSR in cetuximab

 marypatlynch 

Do you have a specific question?

 desphippsrn 

We seem to have a lot of HSR  (hypersensitivity reaction) in my area. I was wondering if others have this as well and what the management protocol should contain.

 marypatlynch 

We do see some reactions. Literature says 20-25% of patients will have an infusion reaction. We usually premed with benadryl.

 lkrioux 

I have heard that cetuximab patients that have IGE antibodies (especially in areas like ours: TN, AR, KY, and NC) may be more prone to anaphylaxis and they need to be loaded with Benadryl up front.

 desphippsrn 

We use Benadryl 50 mg IV but still have HSR.

 marypatlynch 

Literature says if a mild or moderate infusion reaction occurs (grade I or II) reduce dose by 50% immediately and permanently. If more severe reaction occurs, discontinue the drug.

 lkrioux 

We use Benadryl 50 mg also. We don't seem to have too many reactions, but we are certainly looking for them and will re-treat if necessary.

 marypatlynch 

Regarding IgE, Interesting, I had not heard of a geographic pattern like that.

 desphippsrn 

We have learned of a facility that uses Benadryl, hydrocortisone and albuterol as premeds…

 Kellie 

We pre-treat with Benadryl have have very few reactions.

 desphippsrn 

…then gives 100mg of drug. If no HSR then remainder is given.

 marypatlynch 

So Kellie is from MN and she doesn't see as many reactions, similar to us in PA.

 Kellie 

How are you treating grade 1 or 2 skin reactions?

 marypatlynch 

Patients should be observed for an hour after each treatment and longer if they experience an infusion reaction.

 lkrioux 

Re: skin: Moisturize! Moisturize!

 desphippsrn 

re: observation: is that with every dose or just first dose?

 marypatlynch 

Re: skin reactions, we have had a lot of discussion on that topic in previous chats.

 lkrioux 

I have heard several things regarding skin care: use head and shoulders as body wash, take 3 flax seed/day, rub olive oil on skin. Anyone else heard these remedies for Grade 1 & 2?

 marypatlynch 

Re: skin: We usually start with hypoallergenic moisturizer at the start of treatment, sun avoidance or sun screen. At first sign of erythema we add a topical hydrocortisone 1%, then add topical clindamycin if pustules develop.

 marypatlynch 

Regarding observation for infusion reaction - that is for the first dose as long as they don't have a reaction, if they do, then observation with each dose.

 cjordanoncrn 

What are some good references for guidelines to assessment and management of skin toxicity related to various targeted therapies?

 lkrioux 

Genentech puts out an algorithm for EGFR-related rash.

 cjordanoncrn 

Great!

 cjordanoncrn 

Are there guidelines that cover all targeted therapy related skin toxicity?

 marypatlynch 

Regarding remedies for Grade 1 and 2 - there is a lot of discussion on this topic, especially on patient oriented websites. We usually go with a good hypoallergenic moisturizer.

 lkrioux 

re: Genentech algorithm : the algorithm has not been evaluated in any prospective studies however.

 lkrioux 

We have also recommended Dove body wash that has mild exfoliating properties to help with the dry, itchy skin.

 marypatlynch 

There are two good articles that I like: Beth Eaby's article in CJON April 08 issue on managing skin reaction associated with EGFR receptor inhibitors..

 marypatlynch 

second article - Karen Oishi's article in Forum first issue 2008 on clinical approaches to minimize rash associated with EGFR inhibitors

 cjordanoncrn 

Sorry to barge in. feel free to continue to explore the prior question prior to answering mine:) Thanks for the references too!

 desphippsrn 

We also use doxycycline 100mng BID × 10 days

 marypatlynch 

It’s good to use articles that have done some evaluation analysis, like the ones I mentioned, Eaby's article has a proposed algorithm in it.

 cjordanoncrn 

Thanks for the advice regarding use of articles.

 marypatlynch 

Yes, once the rash has become severe we add doxycycline oral as well.

 cjordanoncrn 

Will the text of this chat be available once the chat is complete?

 cjordanoncrn 

I came in a few minutes late and probably missed some things.

 marypatlynch 

How do you manage compliance with the oral drugs? This has been a topic of discussion in previous chats.

 Laurl at ONS 

Yes, the transcripts are usually posted a day or two after the chat happens, back on the Hot Topics webpage via the ONS web page. Please feel free to print and pass around - We have heard that the transcripts have been useful for discussion purposes after the chats are over.

 marypatlynch 

Regarding rash, although it can be an acne-like rash, it’s important that patients not use OTC ( over the counter) acne preparations as they can be severely drying to the skin.

 knooptj 

Back to the IgE issue with cetiximab. We also have a higher than normal severe HSR rate here in Nashville. Here are a couple of good articles related to the problem and management of the problem. Chung C, Oncologist June 2008 and Chung C et al NEJM March 20

 lkrioux 

Thank you for the article reference knooptj

 Laurl at ONS 

Great references - thank you.

 marypatlynch 

Many targeted therapies work by focusing on proteins that are involved in the signaling process. By blocking the signals that tell cancer cells to grow and divide uncontrollably, targeted cancer therapies can stop the growth and division of cancer cells.

 marypatlynch 

Thanks for the references, very interesting topic. Is there any hypothesis about why the IGE levels are higher in those areas?

 marypatlynch 

Depending upon the proteins involved and growth factors involved, the side effects of these targeted therapies may be different.

 lkrioux 

I know some have speculated that a skin reaction can be predictive of response with these agents, is there any evidence that this is true?

 marypatlynch 

Good question, there have been studies which show that a skin reaction is predictive of response, this is believed to be due to an inflammatory response as a result of EGFR inhibition in skin tissue.

 marypatlynch 

It’s also helpful to let patients who are dealing with this uncomfortable side effect know that this may mean that the drug is working.

 knooptj 

IgE antibodies against galactosealpha 1, 3 galactose were found in the serum prior to…

 lkrioux 

The person that presented the IGE theory did not give rationale. Maybe it's the Cherry Blossoms. smile.

 marypatlynch 

Maybe :-)

 lkrioux 

I'm afraid I have to step out for a meeting. Great discussion. I can't wait to read the transcript.

 knooptj 

Sorry I cut off my answer. …prior to the infusion of cetuximab. galactose alpha 1, 3 galactose is a molecule found in cetuximab, but obviously pts were exposed and developed these antibodies prior to cetux, thus having severe reactions to that first dose of cetux. I don't think anyone is yet sure of what the prior exposure is related to. Not many cherry blossoms in TN, but who knows?? :)

 desphippsrn 

few cherry blossoms here in KY, but LOTS of reactions.

 marypatlynch 

There is an article in the March 2008 NEJM regarding hypersensitivity reactions to Erbitux associated with the IgE antibodies to galactose alpha 1,3 galactose, its a sugar chain, there were higher rates and clusters in several SE states.

 marypatlynch 

JCO 2007 found grades III and IV hypersensitivity reaction to Erbitux in TN, NC.

 desphippsrn 

We see more HSR in our head and neck patients

 knooptj 

I believe an assay is being developed to determine which pts may have prior exposure to galactose alpha 1,3 galactose which could make them a higher risk for severe HSRs with cetuximab.

 marypatlynch 

According to these articles, the regional differences are not clear but they are looking into it, there are a lot of hypotheses including things like exposure to ticks.

 desphippsrn 

interesting

 marypatlynch 

re; head and neck patients, it may be that you are seeing more hypersensitivity reactions in those patients because they are already compromised with airway and skin issues

 desphippsrn 

so very true

 marypatlynch 

What other side effects from targeted therapies are you seeing?

 Laurl at ONS 

Mary Pat, any tips on improving compliance especially related to oral chemo?

 marypatlynch 

This is a hot topic, there are some really good references posted at the bottom of the transcript from the first chat that give information on safety and compliance with oral drugs. lots of sites are developing guidelines for this issue.

 desphippsrn 

Many thanks to all. Must run. Will catch conclusion on the transcript.

 Laurl at ONS 

We have about 5 more minutes- please continue to ask your questions! Also, at the end of today’s chat, please take a moment to cut and paste this URL into your browser and take our very brief survey- we’d love to hear what you think of these chats! The URL is: http://research.zarca.com/k/RsTUTRsSPYsXYTSTsPsP THANK YOU!

 Laurl at ONS 

Any other last minute questions?

 marypatlynch 

Thanks everyone, have a good day!

 Laurl at ONS 

Well, it looks like we are about out of time! Many thanks for a great discussion. This transcript will be posted tomorrow. Please check back for future topics and dates -

 Laurl at ONS 

If you have a topic you'd like to see covered in future chats, please let me know!