Increasing Alectinib dose - 1290397

jmpchic
Posts:34

It's been a while since I've posted. Brief summary...husband diagnosed 2010, cis/Alimta, 2011--ALK---xalkori, 2015--liver mets, switch to ceritinib, tolerated poorly requiring two dose reductions, 2016--pancreatic met---switch to Alectinib with cyberknife to pancreas. March 2017---liver mets... Currently we are awaiting repeat molecular studies to proceed with next step. My question is this...Is it possible the Alectinib just hasn't had adequate time to kick in? He had a two to three week hold before switching to Alectinib due to toxicities. I've seen other patients who have increased Alectinib dose to 900 mg bid. Just wondering thoughts on when to abandon one drug for the next. This is the first time we haven't had a drug to go to without being on a study.

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catdander
Posts:

Hi jmpchic,

I'm sorry to hear your husband has experienced progression again. It's usually not suggested to increase dose of a drug. The reason is when a drug is in testing the first test is to find the highest dose that can be tolerated without an over abundance of adverse effects. So the highest safe level is built in before testing for efficacy.

It's possible the time between drugs allowed the cancer to grow. If there wasn't a scan taken just before starting alectinib the new growth may be the product of no drugs and not alectinib. If so continued use before another scan would most likely answer the question. A lot depends on how your husband is doing, it's important to stay ahead of cancer related symptoms so they don't become too bad to turn around or be eligible for a trial.

If your husband didn't progress or take alimta alone then alimta is an excellent option for treatment. Regular infusions at the cancer center aren't as attractive as taking a pill at home but alimta has shown to have long lasting efficacy especially it seems in people with ALK rearrangement.

You've probably watched our series on acquired resistance in targeted drugs. Some drugs have been added since the seminar but the thinking behind how to manage is still the same. here's a link, http://cancergrace.org/lung/acquired-resistance-patient-forum-2014-vide…

I hope your husband does well moving forward.
All best,
Janine

JimC
Posts: 2753

Hi jmpchic,

[It looks as though Janine posted her response just before mine, but here's mine anyway]

I'm sorry to hear about the progression to the liver. As far as whether alectinib has had enough time to show a response, I can't tell from your post how long your husband has been taking it, but normally the best response to a TKI is seen fairly quickly after starting it. So if it's been a month or two, I think it's had enough time to be able to judge whether it's having an effect.

On the other hand, since there was a gap between regimens, it is possible that the pancreatic met developed in the interval between the scan on which it was first seen and the start of alectinib therapy. If that's the case, then the appearance of that pancreatic met might not indicate a failure of alectinib, especially if the disease is stable elsewhere. In addition, since the pancreatic met has been radiated, if there is otherwise stable disease it might be reasonable to continue with alectinib.

JimC
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jmpchic
Posts: 34

I should have made things a little more clear. He had control on ceritinib but just couldn't tolerate it. So he had a 3 week break before we decided to start Alectinib. In the meantime we got a scan as a baseline before starting alectinib and that is how we saw the pancreatic met. He started alectinib Dec 10 with radiation in January to the pancreas. March 5 was his follow up scan from starting alectinib and radiation. So he had 12 weeks alectinib prior to scan. The March 5 scan showed 2 new liver mets. I guess we are grasping at straws hoping to stay on Alectinib because he is tolerating it so well and honestly just hoping this was a fluke and it really is working... this is the first time we haven't had a new drug to go right to and it's scary... We have sent for repeat molecular studies and continuing alectinib until we see Dr. Shaw on 4/11. Although I have begged for an earlier appointment! One liver met was ablated at the time of biopsy and the second left for measurable disease purposes in case we go on study. Our onc has discussed Alimta. Jon did do about 5 or 6 treatments of Alimta alone but stopped due to increasing toxicity and also because we had xalkori to go to. He has responded so well for so long and this has felt like a kick in the gut.

JimC
Posts: 2753

Hi jmpchic,

Thanks for the additional information, which makes your husband's situation much clearer. I think Janine's suggestion of a return to Alimta is a reasonable approach, since he didn't discontinue it due to progression. Perhaps the toxicity issue could be avoided or lessened by decreasing the dosage or lengthening the infusion cycle from the usual three weeks to four weeks. Of course, that would depend on the nature of the toxicities he experienced, and would be a good topic for discussion with his oncologist.

Will there be another scan before seeing Dr. Shaw? That might provide a good indication of what's going on while continuing to treat with alectinib, although it may be a bit of a short interval.

In addition to Alimta, docetaxel (Taxotere) would also be a leading candidate in terms of standard chemotherapy, as it has shown good efficacy in pre-treated patients.

I hope you have a good meeting with Dr. Shaw, and that a good treatment plan is put in place as a result. Knowing the next option could certainly help to ease your concerns.

Please keep us updated.

JimC
Forum moderator