In month 3-4 of my participation in the afatinib/cetuximab trial, I developed painful fissures in my fingertips and soreness due to inflammation. Reaching into my purse could be excruciating and Blackberry use a challenge.
Following my most recent combo chemo/radiation treatment, I restarted Tarceva. The 3rd independent Tarceva treatment period. Each time the skin reaction have been a little different. This time, in week 4, my finger tips and cuticles are VERY inflamed (more than BIBW trial). My hands and lower forearms feel as if they have been scalded, generating noticeable heat to the touch. Blistering appears at the side of the cuticles and the "paper cuts" proliferate and bleed if they get bumped. I've been adopting Jing's treatment solutions and found Aquafor and liquid bandaid to help the most.
I saw the dermatologist today. I was impressed that he had read my whole chart and had done significant reading of the current literature on this topic. He was well informed and interested in documenting my experience in order to build his understanding of how EGFR and similar treatments affects patients and what strategies seem to be most effective.
BTW, he entered the room, greeted me and said, "You look great! Your chart looks awful, but YOU look GREAT!" LOL!
He prescribed Clobetasol 0.05% ointment, applied to hands twice daily for up to 2 weeks and then twice daily on weekends only as needed. (may be repeated every 2-3 months as needed for flares). Potential side effects: skin thinning and striae (stretch marks). Less "burning" tonite.
Also, each time that I have restarted Tarceva, I have developed clear white bumpsthat look like blisters on my nose that don't go away. He said that these are blocked pores...blocked deeper beneath the skin surface. He prescribed Differin (adapalene) 0.1% cream (something he commonly prescribes to patients with acne). It is possible that this will reduce the inflammation and open the pores so that the bumps will subside.
Casie, given the awful time you have had with side-effects, I am glad you are off the trial. I am very impressed that you put up with it for so long. I really hope investigators for these agents take note of how difficult the side-effects can be.
Just wanted to check that you and everyone on this thread were aware of Dr Lacouture's new book on skincare - Dr West wrote a post about it:
The update on Jing is here:
Craig, thank you for the tip.
Casie, my sister is not getting the combo through 'regular' channels. She's receiving Afatinib through the company's compassion program and her onc is the one prescribing Cetuximab. A bit unusual, but as long as it works...I hope you can find a tolerable and effective treatment soon and I'm glad that you're feeling good while on treatment break. The side effects of Afatinib can be quite horrendous. I agree with CS that investigators will have to find something to control these, as side effects are often so bad that patients have to stop treatment. My sister is now on a reduced dose of Afatinib (30 mg). I hope it will help (she also had horrible rashes all over her body recently).
Blue Skies, I hope that what your dermatologist prescribed will help you quickly, and that side effects will become manageable so that you can keep on taking Tarceva.
Take care everyone,
FYI -- if the side-effect that gets so bad the drug must be stopped is the same kind of rash that Tarceva often causes, in addition to remedies to help you deal with the effects of the rash you might want to discuss these refrences with your doctor on the subject of things that neutralize the Tarceva but hopefully only topically in the skin:
Jump to the paragraph near the end just after Table 5. Read that & the research citations it cites.
We are awaiting research results from this trial. The most important thing would be whether it can neutralize the Tarceva in the skin without neutralizing it in the body.
3. If the above research trial finds that topical vitamin K doesn't penetrate into the body and neutralize the Tarceva in the body (thereby stimulating the EGFR mutation despite the presence of Tarceva), an Rx pharmaceutical-grade cream would become available from Talon Therapeutics.
(You might also be able to find a consumer-grade cream that includes vitamin K3 (or the weaker K1) but not in medicinally-approved and controlled concentrations, e.g.,
Of course you should not do anything that would disrupt a drug trial's protocol and should not try experimental things that aren't at least under the direction of your oncologist.
Stage 4 ROS1+ [mucinous BAC] adenocarcinoma NSCLC since 2011
Xalkori (crizotinib) 5 yrs
Alimta (pemetrexed) + carboplatin (mere months)
TPX-0005 (repotrectinib) TBD (1+ years as of Fall 2018)
Craig, Just wanted to say how impressed I am with your knowledge and your willingness to share. Good luck and very best hopes to you,
Wow Craig, that's really helpful! Thanks a million,
Janine (catdander) -- Thanks, but sometimes it is better to be lucky than smart. I was lucky to stumble across those references in my meanderings (and maybe a little smart enough to recognize it might be interesting to someone someday).
Myriam (fortmyr) -- Always glad to help if I can. (I just wish I didn't miss so many new discussions because there's no way to get email alerts of them.)
I have tried to keep up with the activities and information about this trial for one and half years. This is what I wrote on my notebook: This trial showed good initial results (e.g., 2011 ASCO poster). However these results seemed to fade away and adverse side effects were prevailing (based on participants’ experiences). This is not desirable, if the goal is to extend the quality life.
Yes, I must confess I am extremely confused about this trial. It obviously helps some people for a time, and that is wonderful. Jazz is a case in point. But our doughty pioneers (blueskies, pedalon, jinz's mother, Jing, Casie, for example) have all eventually had to retire and move on to other treatments. And the side-effects have been often overwhelming, as AB says. So it obviously isn't the magic combination we had all hoped for.
I would value a doctor's comment (when convenient) on what we have learnt so far, if it is not too early for that. I also thought that the trial was being expanded, rather than closed as Casie suggests - does anyone have further information about what the position is now? And does the trial combo work better in people exhibiting the T790M mutation, as Craig's abstract from Pao et al implies, or do we not know that yet?
Honestly, I haven't heard much at all. The last I had heard was that the trial was going to be expanded, but I suspect that business decisions have supervened -- primarily that the company is focusing on getting an FDA approval for afatinib in the US as a first line treatment for EGFR mutation-positive patients, based on the LUX Lung-3 trial results. I personally don't find those results especially compelling -- pretty much just what I'd expect with Tarceva (erlotinib) or Iressa (gefitinib) in the same population, but more severe and prevalent side effects -- but in the gamesmanship that is the world of big pharma, that's probably good enough to get approved.
The company (Boehringer-Ingelheim) may well presume that once afatinib is commercially available, patients and/or doctors will use it with Erbitux (cetuximab) in the setting of acquired resistance to Iressa or Tarceva whether it's well really studied or not. They may well cautious about studying it further because they suspect that holding it up to the light better will lead to a conclusion that it's really not very effective and/or is prohibitively toxic. So if they aren't confident it's a major improvement, they may figure they're better off not studying it much and letting people be hopeful (kind of like the adage, "Better to keep quiet and have people assume you to be a fool than to open your mouth and prove them right").
At the same time, companies that have a drug nearing FDA approval typically like to pare down research efforts because any new problems that emerge in the 11th hour have a real chance of complicating the approval they're counting on.
Dr. Howard (Jack) West
Associate Clinical Professor
City of Hope Cancer Center
Founder & President
Global Resource for Advancing
Thank you, Dr West.
And the idea that the combination might work particularly well for people with a T790M mutation - is that wrong/a red herring/not proven? I ask because, if that were true, it might motivate some patients to ask for re-biopsies at the time of progression, to look for T790M.
Although the dry skin and inflamed fingertips on the afatinib/cetuximab trial were challenging, they were not debilitating for me. I was glad to have an initial 20% reduction in tumor size and 4 months of disease control. And Jing, our super-responder got 9 months of disease control.
I am glad that the researchers appear to have demonstrated an "average" response duration of 4 months that may help them assess efficacy and problem solve the resistance pattern...you couldn't know that going in, so the trial participants move the level of experience and understanding forward. I
t will be interesting to see how the T790 positive cohort did compared to the T790 negative group. I did have a rebiopsy to test for T790 status. And I'm about to have a third biopsy for the comprehensive molecular marking inventory, which will help determine my eligibility for upcoming trials. I think the days of a a single biopsy are probably gone - especially with the pace that research moves the need to know more details about the chemistry and action of the cancer.
Forgive me, but even though I resented not incinerating my primary tumor early on or over the course of my treatment (it was like an unwanted pet that I had to keep around), the fact that I had a new met to my adrenal gland to biopsy turned out to be a good think for the NIH and future clinical trial eligibility determinations. It is doubly irritating to have cancer but not be able to get enough biopsy tissue to do you any good!
Dear GRACE faculty and friends,
Thank you so much for your concern and care while I was changing the course of the treatment and getting over the new road bump after 5 1/2 years after into the fight. I, of course, must thank my dear friend/sister blue skies for constant encouragement and comforting emails. There is so much to tell, but the back pain, discomfort and fatigue have kept me from sitting down to write. In the past a few days I have started writing in a Word file when I felt like to without a clear idea what I was writing. Blue skies has put my recent update in the thread of Community Updates. I will write a few short posts to fill in the details. I think I should finish at where I started with, so I am posting here.
First of all, best wishes to Jazz. I hope the trial drugs will work for you as long as possible. Though the side effects are terrible, I always say to myself that I prefer dealing with the side effects to dealing with the tumors.
After the spine rad I do feel that the back pain improves over the past week. I take much less pain killer now that had irritated my digestive system and made me lost my appetite. I am happy that I can eat more now.
(more to come)
Somehow after resetting the password, it seems I am assigned a new account with ID Jing. How to get FaithAndHope79 back?
Try logging out, then use the password recovery button on the Login page again, using your old username: FaithAndHope79
That account is still active, so you just need to access it using that username instead of "Jing."
It's so good to hear from you. Yes, it can take a little longer for pain to resolve after radiation. don't push yourself too hard.
Yes, great to hear from you and sorry for all you've been through recently.
I tried again, but in the email it insists that my ID is Jing.
Someone requested that the password be reset for the following account:
If this was a mistake, just ignore this email and nothing will happen.
To reset your password, visit the following address:
Anyway, I suddenly recalled the password for FaithAndHope79. Now I have logged as it.
Thank you for your quick response.
Hi Jing, It's good to see that sweet little girl in your avatar. Didn't you say that was a drawing someone did of you? Your brother?
I hope you're feeling better each day.
It's a portrait ofJing's sister as a child, I think - her sister being no longer with us. I agree it is very nice to see the picture again!
Janine, CS is right. It is my drawing from a picture of my older sister, taken when she was 5 years old. She lost her battle to breast cancer 3 years ago at age of 49. Her husband lost his battle to liver cancer a year later at age of 50. I miss them every single day. That is the reason that I have not told my mother (my father has passed away) and my younger brother about me. They have been through too much.
That's very hard. I am sorry for the loss of your sister and brother-in-law. It's a lot to carry. You're very brave to cope with all this on your own.
Forgive me, as this is absolutely none of my business, but I wonder if your mother and brother might want to know about your illness, however painful the knowledge might be? As one of my brothers said to me, "This is a good time to express love". Maybe you will tell them one day. Everyone deals with this in their own way. And you've managed so incredibly well.
Hi Jing! Thanks for the well wishes. It's good to hear from you, we've been very worried. I hope the radiation gives you relief and you can get around again. Glad that you have your appetite back, too.
What treatment have you moved on to, besides radiation? Whatever it is, I hope it'll keep things under control for awhile.
Blue skies, have your docs mentioned any other tx to get at the adrenal met besides chemo/bio agents, and have they mentioned anything otherwise as to difficulty in treating that sort of thing? I ask because I only recall one other instance of hearing about adrenal mets.
My doctors are acting like this is just part of my systemic disease. No one has mentioned if ther is anything "special" about it showing up my my adrendal gland, but I would be interested in looking at information about that. I think I'll use GRACE's wonderful search engine to see what I can turn up.
We are looking at clinical trials right now and holding more traditional (and ugly) chemo options for future.use.
I confess I too was surprised by what Jazz says, as there seem to be quite a few references to adrenal mets on GRACE. Perhaps a doctor could put us straight.
Adrenal mets are really part of the same process as other systemic disease. In situations where it is the only area of metastatic disease, an argument can be made to treat it with local therapy. However, when it's one metastatic area among several/many, it really doesn't have any particular significance -- there is no reason it would warrant being treated in a special way.
Thanks Dr West.
Thanks, gang. I was actually thinking of adrenal mets as being Kidney mets, and thought of kej's husband. But the adrenal gland is simply connected to the kidney...
It's actually not even connected...just on top of it.
And while kej's husband did pursue aggressive local therapy, that was still really above and beyond standard treatment, and in the end, his cancer unfortunately acted like metastatic disease, and I'm not sure that intervention helped.
My sister had her first injection of Cetuximab yesterday. This morning her husband phoned me. Unfortunately, she had a very bad headache last night (her head was seriously throbbing) and she also vomited once. I read in the Cetuximab monography that headaches and nausea are common and non-threatening with this type of treatment. However, I was wondering if vomiting is more serious (the company suggests to contact a doctor when this happens). My sister is now sleeping. I'm spending the day with her to make sure everything is OK. She has not vomited again since last night so may be it was just a one-time side effect?
Any knowledge that you have with respect to the Cetuximab side effects will be more than welcome,
My sister just woke up and she's feeling much better. She still has a bit of a headache but things seem to be going back to normal, thank God! She ate some late breakfast and will be going back to sleep to recover fully.
so good to hear.
Myriam, sorry for the delayed response. Yes, flu-like symptoms are common after the first infusion but your sis shouldn't experience them again. Also, maybe check on the benadryl dose that they probably gave her prior to infusion. If it's really high (50mg) it can also cause dizziness/nausea. I had severe chills, fever, and a raging headache for two days after my first infusion.
Wishing the best for your sis, I hope cetuximab helps her. I personally feel it's necessary and feel much better after an infusion! Thanks for keeping us posted and please feel free to ask anything. Hopefully we can all answer quicker!
Just kidding. Update: I'm now on Cycle 9 of this trial. I've found the study can be flexible as regards holidays! BI is allowing me 3 weeks between treatments so I can go to New Zealand!! Will mostly be on the south island. Ann (Pedalon) said it was the most beautiful place she'd ever been to; I plan to send off a wish lantern in her memory from some scenic promontory.
When I return I'll have a CT scan and hopefully go on to Cycle 10. If not then I'll have to do some fancy dancing to either get into the Clovis trial or see if a little bird can spot an open anti-PD1 trial nearby. If a fresh biopsy is needed they'll have to take it from the collapsed lung or...???
Meanwhile I'm in a health insurance quagmire. Is there such a thing as being over-insured (aka wasting money)?
Myriam, I hope your sister is making some gains.
That sounds like a wonderful trip you have planned. I believe Ann will appriciate your wish lantern.
Are you on medicare? D's blue cross individual changed to medicare in January and I chose blue cross, blue advantage, a medicare approved ppo. It is much like his individual blue with co pays and deductable. I think it's fairly new but we don't have all the donut holes and odd bits that going directly through medicare must have had. So far I haven't found anything odd,...except you've reminded me 8-O ...the last perscription he had filled charge the full generic price and I needed to call (drugstore spent about an hour trying to figure it out). This was last week and we were on our way out of town. I'll do it soon and report back.
Jazz, glad to hear about your trip to New Zealand. I'd love to visit NZ sometimes. It's supposed to be really beautiful.
To answer your question, my sister does not seem to be benifitting a whole lot from the Afatinib-Cetuximab combo. We went for a walk yesterday, and I asked her if she thought it had some effect and she said that she did not believe so. However, she added that at least the pain was not worsening, so I guess it's kind of a 'steady state'. The problem is her right lung is so full of fluid. Her oncologist is advising against draining it as he believes that the pleura is in such a bad shape that draining it could only increase the pain level. Furthermore, but that's only my opinion (not her onc's) I believe that if the cancer is not controlled by the treatment my sister's lung will fill right back, so it will be of little use to drain it only once.... What she'd need is something like what Dr. West described in another thread: a permanent drain. Given that I will be going to her appointment with her onc tomorrow I'll be able to tell you more about her options soon. It's really though for her as it's now to the point where her lung is so filled that she will prevent herself from drinking or eating at times so as to decrease the pressure on her lung. I really hope that her onc can offer her some relief. I'll keep you posted.
I'm sorry to hear that whatever the Afatinib-Cetuximab combo might be doing, it's not noticable.
I wonder what the next most-promising 3rd generation drug or combo might be for resistant EGFR? (Or maybe a not-mutation-targeted kind of drug, like the BMS or the MK anti-PD-1 drugs???)
Thank you Craig. Best wishes to you,
Hi, everyone. Thank you very much for sharing with your experience on the trial. I wonder whether there is any one with brain mets having benefited from this trial? Is there any new developments on this trial, for example, the latest data on efficacy? Hope there will be more news coming up soon.
Special greetings to Jing, wish everything is well with you. We met each other on another website.
Good luck to us all.
Still here, still on Afatinib+Cetuximab at U of Colorado. My next scan/visit with Dr. Camidge is on the 12th. If it's alright, I go on to Cycle 12. I'm coughing quite a bit more lately, so I'm apprehensive.
Side effects are roughly the same - paronychia sufficient to warrant a visit to the podiatrist. The soles of my feet are often raw and tender, necessitating frequent use of liquid and regular bandages. Same for the finger splits. For the crusty eyes I now use Azithromycin drops and polymycin/bacitracin ophthalmic ointment. No permanent solution for the crusty nose, or the inflamed scalp and eyebrows. I've tried BioSmooth fluocinonide scalp oil, which helps the dryness but still stings the rashy areas. And wearing a shower cap to bed is sure to move one's husband to the guest room! It's all a big bummer but I'm grateful for the 7th Christmas after Dx...
I took my father to see Dr. Ou at UC Irvine for a 2nd opinion. Dr. Ou will have a clinical trial for an oral HSP-90 inhibitor DS-2248 (Daiichi Sankyo) early 2013. It'll be Phase II, requires EGFR+, T790+, or acquired resistance to TKI. I'll have to pick Dr. Camidge's brain about it next week and report back. Not sure if it has been posted to the UCI site but it's on clinical trials.gov for those interested.
I've not heard fom Jing, Blue Skies (Ann), Casie, or others who have since come off Afatinib. Yezi, this combination has little activity in the brain, and remaining on the trial is allowed if oligo-mets are successfully radiated.
If I can't stay on the trial, I'm not sure what I'll go to next. MTD has not been reached in the CO-1686 trial. The dose started at 150 and I know someone on 900mg! The good news is there are virtually no side effects (some muscle pain?), the bad news is I have to wait for the Phase II expansion cohort (2nd half 2013?) for Kaiser to approve it. But maybe I can find away around this...
Until next time,
Best to all,
Dear Jazz - So glad to see you back. Your poor feet, I can't bear to think about it. So unfair.
I too have been wondering about Jing, Blue Skies and Casie. Would love to hear from any of them.
Best of luck for 12th.
FYI, I cannot find any lab experiment or clinical trial results info about DS-2248 -- I looked in NIH PubMed, PLoS One, ASCO meeting abstracts, AACR meeting abstracts, ESMO meeting abstracts. (Is there an Asian conference I missed?)
Given its an HSP90, besides asking about any early trial results data on effectiveness, it might be worth asking about toxicities/side effects. If I recall correctly, early HSP90's have sometimes caused damage to some photoreceptor cells in the eye, but that doesn't mean it isn't considered acceptable at some still-effective dose. (Ganetespib was the first to claim it didn't have that issue, I think due to shorter time penetrating eye cells before it cleared from there.) Hopefully DS-2248 doesn't.
I suspect what this tells us is that Jazz is a woman in the know! Looks like there are phase 1 trials of this drug in Michigan and in Texas:
I have to confess that I am terrified of anything that affects the eyes. A GRACE member had serious vision problems with AUY-922 - so bad that he had to come off the trial.
Do you recall who that was, certainspring? I would like to know from them whether the vision problems subsided after coming off the drug or if they were permanent (cell death vs. temporary impairment), and I'd like understand the effect better (did it impaired his ability to communicate online, research online, etc.)
I do - it was a gentleman called Rob, a keen sailor, who very sadly died in January 2011. His wife Leslie was the poster on GRACE, and maintains a blog with wonderful photos at:
Just going by what she posted on GRACE, Rob was on AUY922 as part of a post-crizotinib trial, and had such severe 'ocular toxicity' (vision going from light to dark, big 'floaters' in his field of vision) that he had to be taken off after four weeks. This was I think at UCLA:
For me it was a very sobering reminder that clinical trials can bring with them quite frightening side-effects.
Dr Johnson wrote an interesting post about AUY 922 in October 2011, making the point that researchers didn't yet know where the "niche" for AUY 922 might be (she was testing it for post-Tarceva progression). I wonder if we are any further forward in our knowledge about that yet? This was her post:
It's still in trials, but there haven't been any major results presented with it. The HSP90 inhibitors are being looked at in acquired resistance for both EGFR mutation and ALK rearrangement patients (several HSP90 inhibitors have shown activity in ALK-positive patients), but also in various other cancer settings -- including other cancers than lung cancer. It's fair to say, though, that AUY-922 hasn't yet found its place(s).
I think this may be the trial that i was trying to enroll in most recently at MSKCC, but got closed out of because all the slots were taken...a little more than "VERY DISAPPOINTING" since I was well into the process and scheduled for first treatment the next business day.
As a kind of consolation, the doctor offered that only one of the most recent enrollees in the study at that location had a response to the medication...so still lots tp know and learn!
So pleased to hear from you, blue skies. Have been missing you.
Jazz, and others:
There is an anti-PD-1 trial in UCSF - it uses MK3475. Here's the link
Study of MK-3475 in Participants With Progressive Locally Advanced or
Metastatic Carcinoma, Melanoma, or Non-small Cell Lung Carcinoma
I was looking at this but my onc thinks I won't qualify because you have to fail a few chemo first before you qualify.
When you went on the MK2206+Tarceva trial in UCD, what side effects did you have? I am looking at this trial since it is specifically for those who progressed on Tarceva alone.