Lung Cancer / Mesothelioma
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Loading ...As I’ve described in a prior post, there is some evidence that patients who develop a rash on tarceva (erlotinib) have an improved survival compared to patients who experience no skin toxicity on tarceva. The key question is whether this is an issue of under-dosing some patients, or if it’s just a correlate of overall immune function or constitution in a person, in which case increasing the dose won’t improve the outcome.
The best evidence we have to address this issue is a trial by the Eastern Cooperative Oncology Group, ECOG 3503 (abstract here), in which 137 patients (118 eligible) with previously untreated advanced NSCLC were treated with first line tarceva, starting at the typical dose of 150 mg daily. But the dose was then escalated by 25 mg every two weeks until patients developed either grade 2 rash (scattered bumps or spots or general skin redness with itching or other symptoms) or significant other side effects that precluded dosing up to a maximum of 250 mg per day.
Only half of the patients (60 of 118) ended up pursuing the dose escalation, presumably because the other half already had enough of a rash or other side effects that increasing tarceva dose wasn’t feasible. Only 15 (13%) were escalated up to 250 mg daily. The overall response rate was only 7% (8/112, with one complete response), and the overall survival wasn’t any better than you’d expect.
This trial was actually presented at ASCO last year, but it’s one that we heard almost nothing about. It hasn’t been published as a full manuscript (that’s not unusual, as it can easily take many months or a year or more to get a full paper drafted and accepted in a journal), but I suspect that this information hasn’t gotten out there into the world because the results were pretty disappointing.
But they do make an important point. So to recap, this trial showed that with aggressive dose escalation of tarceva, the response rate was less than was seen in the larger trial with 150 mg and then dose reduction as needed (abstract here); survival was also no better than you’d expect. So this really suggests that there isn’t any incremental benefit to escalating dose. Patients who don’t benefit on tarceva don’t appear to be underdosed. The standard dose of 150 mg per day seems to be adequate, and there doesn’t seem to be an incentive to increasing side effects. This isn’t especially surprising for me, since I see that some of the patients who do very well on tarceva also do it on a reduced ongoing dose of 100 mg or sometimes lower when they’re experiencing toxicity. You don’t need to experience pain to receive the gain.
Posted in: Clinical variables in EGFR therapy, Epidermal growth factor receptor (EGFR)-based therapies, First-line treatment, Lung Cancer, Non-Small Cell Lung Cancer (NSCLC), Rash and other side effects, Stage IV/Advanced/Metastatic NSCLC, Targeted therapies, Treatment
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Dr. West,
I have a question about other possible side effects of Tarceva. I have searched the archives and all of the threads and the vast majority of the comments are about the rash only.
My question is how about shortness of breath and fatigue? I’m currently participating in a clinical trial where Tarceva is given after induction therapy and resection. In my case, I feel as if the progress I was making in terms of lung capacity was stopped, or inhibited once I began Tarceva about 7 weeks after my lobectomy.
My team seemed surprised about the shortness of breath and wanted to take me off the trial(afraid that I could be experiencing an allergic reaction) but I talked them into letting me stay but with a dose reduction to 100mg/day.
So is shortness of breath and fatigue not normally side efects expected when taking Tarceva?
texatl
No, shortness of breath isn’t typical, and I’d be concerned about this possibly reflecting interstitial lung disease, or ILD, which can become serious and even fatal in some cases. I wouldn’t presume that your shortness of breath definitely represents ILD, but pulmonary symptoms are not typical and would raise some concer with me.
-Dr. West
Yes I was worried about ILD as well. I had a XR and CT on Wednesday and I’m told nothing worrisome was seen. Is it possible for one to have ILD and it not show on the scans? My onc went through the progression of slides from the CT showing me how the remaining lobe had expanded and even pointed out what looked like striations on the images as positive sign.
Should I ask for further test?
texatl
Dr West…this is the first time I am writing.My first two scans on Tarceva were remarkable with lung tumor and lymph nodes shrinking so as not to show up on the pet. A new lymphy node in the back above my kidney surfaced however.Now entering my fifth month of Tarceva, I have had a troubling scan showing 25% increase in cancer cells in the lymph noded in my chest. The doctor will see me next week and probably add Navelbene and perhaps another targeted therapy.Naturally I am very dissappointed in these new results after such a strong initial response to Tarceva. Thank you, Jane M
Jane M
Jane,
Unfortunately, we don’t know how best to manage the situation where someone has a nice response to tarceva followed by progression several months or even years later. We haven’t yet found anything that really reverses the resistance that develops — I’ve added avastin for a couple of patients and have seen stable disease but not tumor shrinkage after that. Most often, I’ve favored stopping it and just starting a new treatment that I hope might be effective, but some smart people keep tarceva going and add something else, or they might even try increasing the dose. There’s no right answer at this time.
-Dr. West
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