ALK+, Flare question regarding stopping crizotinib for lung radiation - 1271988

Hi southsidegirl,

Welcome to GRACE. It's not uncommon to hold crizotinib (Xalkori) or other systemic therapy during radiation treatment, and Dr. West has said this about the possibility of a flare (in the context of concurrent brain radiation):

"As for taking a break from the crizotinib and the potential for flare, I’m afraid that too many patients are becoming apoplectic with fear about a flare reaction. While it’s possible for cancer to progress more rapidly on a break from a targeted therapy, it’s very commonly recommended and needed to take time off for side effects, and a few weeks of a break is rarely a major problem. It is often necessary to keep people able to continue these treatments safely. I think some of the discussions of flare reaction really overstate the frequency and anticipated severity: it’s not that people suddenly just explode into a million pieces after missing two days of an EGFR inhibitor or crizotinib, which is what it sounds like people are expecting. It just that it’s uncommon to rare, but possible, to have an accelerated progression of the disease off of it.

...You can always resume it if cancer-related symptoms are clearly escalating quickly. I think if you know to be aware and can be in communication with the doctor, you’re in great shape. I personally think it’s a fine idea to hold the targeted therapy with concurrent brain radiation, and then you can potentially just start it again if needed." - http://cancergrace.org/topic/brain-scans-in-crizotnib-patients#post-126…

Radiation schedules vary quite a bit, to the point where it's hard to say that any particular schedule is right or wrong.

Your biopsy tissue sample has almost certainly been preserved for future use, and can be used for further testing, At present, there are many mutations which can be found, but for which there are not current therapies; it may be best to save the tissue for a specific need, such as use in a trial.

JimC
Forum moderator

1. Right now, all you have had done is ALK FISH test. For the future, I would send the current biopsy for ALK kinase domain mutation testing. (aka Next generation sequencing). This will test for the exact resistance mechanism present. (L1196M, G2012R, etc). Certain drugs are better for certain kinase domain mutations, for example brigatinib may be better for G2012R than alectinib. We have also seen EGFR mutation as a resistance mechanism, strangely enough, in ~10 % of patients. Mind you, this may just give a bit more guidance about future decision making.

2. Regarding lung radiation, it is a bit less common in the USA to give the 'hypofractionated' twice weekly radiation schedule you describe. However, I understand it is somewhat common in other countries, like Japan, to give twice weekly doses, to a total of 4 doses. I am not a radiation oncologist, so I can't comment about whether this is comparable to the daily schedules. In fact, there are at least 5 different stereotactic lung radiation schedules used worldwide, and it is controversial which is superior.

3. I do agree it is prudent to hold the crizotinib during the high dose lung radiation, because these drugs can increase risk of pneumonitis with radiation.