Poziotinib Working

So, the double dose is starting to show its effects.  Some drastic drying/cracking of skin, some mouth soreness (but no real mouth sores yet), and pretty bad diarrhea.  Lots of topical and antibiotic lotion and they said she can up the imodium.  So, it should be mamnageable if she can get the diarrhea under control.  It is certianly wreaking havoc on her digestive system and wiping her out.  She is taking electrolyte drinks to keep her energy and electrolytes up.  But it still seems like a lot less side effects than the TAK-788.  We have a video meeting with the oncologist on Monday, so we will see what they say.  

The Pozi was reduced for a few days to get the diarrhea under control (now very manageable) and they are now going to try 12mg/dy (up from 8).  But the good news is that today's blood tests show the Pozi is still working!  The bilirubin is down again (ever so much closer to normal) and total protein and albumin levels are improving and liver enzymes are also plunging back down to normal!  I will be anxious to see in 4 weeks exactly how much the Pozi has done to the tumors themselves, including the lesions outside the liver.  

Still some side effects (mouth/skin sensitivities), but as I said before, SO much better than the TAK-788 side effects.  And more imprtantly, it works.

Yes, we're crossing fingers, toes, elbows, anything we can find.  

Had new blood test this week - Poziotinib is still working!  SGPT and BUN now in normal range.  Bilirubin and Albumin and Protein better and almost in normal range. SGOT and Phosphatase lower and stabilized, but still above normal range.  Both Lymphocytes and Neutrophils now back in normal range.  RBC and platelets stabilized but still a little low.  The only problem has been the potassium (and sodium a little) which have been a bot out of whack due to all the diarrhea (still a problem).  They are probably going to cut the dose back down to 8mg/dy and then see if they can raise it to 10 mg/dy.

But, overall it is clearly working and in another couple of weeks we will have the CT scan to see what's what.

The other news is that they think my wife has stabilized enough that they can do the spot SBRT on the brain lesions.  I think before the Poziotinib the oncologist felt the liver situation was so dire that there was no need to work on the brain lesions until everything else was under control.  They will wait for the CT scan to see if the Poiziotinib has reduced the brain lesions at all first, and then if not they will schedule the SBRT.

So - we made it through Mother's Day!  (I made one of those cheesecakes!) Our daughter is back in the US and in quarantine, but just a block away!  One day at a time!

Well, just in case you are interested, here is the recipe.....

Layered Lemon Cheesecake with Brown Sugar Almond Crust

recipe adapted from the Junior League of Denver's Cookbookand Creative-Culinary Yield: 12-16 servings

Crust Ingredients:

1 1/2 cups almond flour

1/4 cup brown sugar

3 tablespoons melted butter

Filling Ingredients:

24 ounces cream cheese, room temperature

3 eggs

1 cup sugar

2 teaspoons vanilla extract

3 tablespoons fresh lemon juice

1 tablespoon lemon zest, finely minced, this was the zest from 1 large lemon

Sour Cream Topping Ingredients:

2 cups sour cream

1/4 cup sugar

Glaze Ingredients:

1/2 cup sugar

2 tablespoons arrowroot or cornstarch

1/2 cup water

6 tablespoons fresh lemon juice

Preheat the oven to 350 degrees. Combine the almond flour, brown sugar and butter in a small bowl and stir to combine. Press the mixture into the bottom of a 10" springform pan. Bake for 8-10 minutes. Cool 30-45 minutes before adding filling.

Beat the cream cheese with an electric mixer on high speed until it is completely smooth. Add the eggs, one at a time, beating until smooth after each addition. Slowly add the sugar, beating until smooth and then adding the lemon juice and vanilla. Beat again and then stir in the lemon zest.

Pour over the cooled crust and bake for 35 minutes, until set, but not browned. Stir together the sour cream and the sugar and let rest on the counter while the cheesecake is baking. Remove the cheesecake from the oven and gently spread the sour cream mixture over the top. Return to the oven and bake 12 more minutes.

Remove from the oven and cool on a wire rack for half an hour. Then transfer to the refrigerator and cool for about an hour, until the topping is cool, but not completely chilled. The middle will likely settle somewhat.  While the cake is chilling, make the final glaze. Combine the sugar and arrowroot in a small saucepan. Whisk in the water and lemon juice. Bring to a boil, whisking constantly until thickened. Cook 1 minute and then let cool.

Pour the cooled glaze over the cool cheesecake and spread to cover completely. Chill overnight.  Top with any berries just before serving, if desired. Enjoy!

Glad you like the recipe.

Now as for the news.....

Turns out that prior to today my wife had not had a CT scan since February.  So, today's scan was, um, not good?  That is, compared to February, the scan was a bit worse, even though the blood chemistry is getting better.  Oncologist thinks that the tumors in the liver got much worse during Feb-May, so the current reading is probably better than they were when the Poziotinib started.  I mean in general, other than the Poziotinib side effects, things are much better than they were 2 months ago.

One small high point - the brain lesion is slightly smaller.

So, what to say.  Overall, the liver is about the same as it was 3 months ago, as is the blood chemistry, but we have no CT scans to see how bad the lesions got during the bilirubin peak.  Her health is generally better (rash, exhaustion, edema, jaundice are all gone), so we know the poziotinib is working, but I guess we really won't know how well (on the physical lesions) until the next CT scan.

But, because things don't look worse in the brain, and perhaps a teensy bit better, they will likely be going ahead with the SBRT.

My wife just had a CT scan and blood tests this last week, and well..not so good.  CT scan showed progression everywhere - lung, liver, and brain.  Blood work also showed that the bilirubin is again going up (although most of the other liver enzymes are stable).  Her coloration is definitely again showing jaundice, although the body rash and edema she had before aren't showing up.

The oncologist talked to the specialist in Texas and the specialist had two suggestions - one was what he had talked about at our meeting in March, using Kadcyla along with the Poziotinib (some initial possible evidence that it works better with/after Poziotinib) and he thinks a new drug Enhertu might be even better, but we have to get special permission to use it (currently OKd for breast cancer but not lung cancer).  So, my wife starts on some Kadcyla next week, and will probabkly switch to Enhertu once we get permission for it.

This will be the last entry in the Poziotinib section (probably) as my wife got approval for Enhertu (after all those exciting drug names - who came up with this one - based on En-HER2, so boring...).  So, as usual, for anyone taking the time to read the thread I offer my thoughts on the pros and cons and side effects of Poziotinib.

It clearly, and literally, was a lifesaver for my wife.  We had be given the "talk" by the oncologist in case the Pozi didn't work, and had more or less been given 4-8 weeks for Sara to live.  Within days of getting the Poziotinib the whole body rash went away, the edema started going away, and her coloration started to get better.  Within 4 weeks her liver blood enzymes were almost back to normal.  It seemed (at the blood chemistry level) to work well for about 8 weeks, then less so.

The dosage for Pozi is definitely tricky.  While the maximal dosage of 8mg twice a day is what to shoot for, most people apparently end up at 12 mg, and for many the side effects are less at 6 mg 2x a day.   My wife found (as apparantly some others have too) that the heartburn side effect is actually better taking more at night - 0,2, or 4 mg in the morning and 8 mg at night.  Apparently, since Pozi is a kinase inhibitor, the cells start generating an increase in the HER2 kinase to compensate for the inhibition.  Thus, it was not surprising that the 8mg my wife started with (and was effective) stopped working well after a while.  But the side effects definitely go up with dosage.  For my wife, the diarrhea at 12 mg was almost unbearable (and difficult to control) while that at 8 was much more manageable.  On the other hand, whenever she tried reducing the dosage she felt much worse (more gneral aches and pains and lethargy) at the lower doasge than the larger dosage, even though the diarrhea was better.  Whether this was due to the cancer itself being less restrained at the lower dosage, or some realteration of body side effects is hard to know.  So, my wife was trying out a 10 mg one day followed by a 12 mg next day regimen when the Enhertu was approved.

The effectiveness of the Poziotinib is hard to gage - definitely great effect on restoring liver function at 8mg, then 10mg for a couple of months, and then the liver function deteriorated until she had a little time at 12mg.  But, throughout the time of Poziotininb there appeared to be no constraining the actual size of the cancer, and during the time the liver function started to decrease again there were definite increases in size and number of cancer lesions.  Whether or not the cancer stabilized as the liver function stabilized reamins to be seen.

So, onward to Enhertu!  The preliminary data is extremely encouraging, as this, like Kadcyla, is directly focused on HER2 cells, but also seems to work for patients who progressed (like my wife) on Kadcyla.  Moreover, there is some thought that the increase in HER2 receptors on the cancer cells that are stimulated by Poziotinib might actually increase the effectiveness of Kadcyla and Enhertu, since they bind directly to HER2 receptors (then get into the cell and deliver a poison, although they each have a different poison).

So, today is the first Enhertu infusion - I will keep everyone updated on how it goes!