Must I actually stop Crizotinib? Or can I still take Xalkori? - 1241757

Thu, 03/22/2012 - 23:37

I’ve been on a Crizotinib clinical trial for 10 months. Recent back pain prompted my Dr to order an MRI on my back and it showed activity on my spinal lesions. Not so much as to threaten my spinal cord yet, but enough to warrant having certain vertebrae radiated as a pre-emptive and pain-killing move.  However my CT scan, done the day before the MRI, shows the drug continues to be effective against the original tumor and other small metastatic tumors in my kidneys and liver (one on my kidney has even been “no longer visible” for two months).

The need to be radiated means, just as part of the protocol, I have to be taken off the clinical trial. I will start Alimta infusions in lieu of the Crizotinib. 

I’m disappointed that I will no longer be taking the Crizotinib since it does seem to continue to show effectiveness in some areas, and I can see that I should take a break from it if there’s a medical need to do so, concurrent with radiation.  But I would like to continue with it after the break.

Is it possible to make this sort of choice, i.e., stop Crizotinib because of the rules of the clinical trial, be radiated, and then take up once again on “Xalkori” afterward? Wouldn’t it make more sense than starting Alimta, if the drug has shown effectiveness? Or are we betting that the Alimta will show effectiveness against the bone lesions where the Crizotinib has stopped being effective?

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certain spring

Hallo Ken. Sorry to hear about what's going on with your back, though perhaps the scan results help to explain some of the pain you've been having?
I wanted to draw attention to your post as this seems an important question - how to deal with a situation where a targeted drug is still working on some parts of the body, but there are new problems elsewhere. I'm also wondering if anyone has ever tried Alimta and Crizotinib together, given that they both have activity in a person with the ALK rearrangement? Very best.
PS: Just thought it might be useful to link to Dr West's posts about the efficacy of Alimta in people with the ALK rearrangement:


Hi, Sorry you are not getting the results like you once did. I do not think there are any trial w/ xalkori/alimta. I see one that includes all three. the third being cisplatin but I do not think you want to go there.
I am interested to hear what the docs say because I posted the same question on another site and believe no one is on xalkori/alimta. I do not know why they have not studied this combo because I think it would be a no brainer. Hopefull you will be able to go back on xalkori w/ a persrcription in the near future. good luck. Sean

Dr West

This situation of acquired resistance to crizotinib is really the remarkably analogous to the challenge of what to do for patients with acquired resistance to an EGFR tyrosine kinase inhibitor (TKI) like Tarceva (erlotinib) or Iressa (gefitinib) -- progression after a very good, long response. Is there still a significant subpopulation of cancer cells that are sensitive to the same targeted agent? In the setting of only mild progression but otherwise good control, I'm tempted to continue the same targeted therapy and add chemotherapy to cover the progressing subpopulation of cancer cells. On the other hand, if the progression is very significant, I would be more inclined to favor switching to a new angle and moving on from the same targeted therapy -- though perhaps returning to it after a break, in case the cancer becomes resensitized to the agent that was previously but is no longer effectively suppressing the cancer.

Overall, though, we still don't have clear signals about the best approach in acquired resistance to EGFR TKIs, and we're years ahead there compared with acquired resistance to crizotinib (XALKORI). I think it comes down to careful judgment and an individualized plan rather than any clear rule here.

Good luck.

-Dr. West