分享一下 - Jenny Mao, Lung Cancer, Xalkori
On hearing news about Jenny Mao's passing, I felt pretty guilty - I should have done this sharing long ago, with other patients and families in the lung cancer community, especially in the ALK/ROS1 positive groups where both Jenny and I belong
this is what I know about m8888 -
her name is Jenny Mao;
she has been quite active on lung cancer sharing website: www.inspire.com, also known as m8888;
she lives somowhere in between Seattle and Vancouver;
she has same molecular type of lung cancer as me, ALK+ (ALK 基因重组阳性) lung adenocarcinoma;
last I knew about her was that she had been on Xalkori for 24 months. I did not know she was sick;
I started communicating with her in spring 2012 when she appeared on Wenxuecity asking for help - I believe that was when she started targeted therapy treatment with Pfizer's drug Xalkori.
Back then, I was still on Xalkori (crizotinib) but the drug had about lost its effectiveness on my cancer. I started clinical trial of Pf-02341066 in 2010 (later known as crizotinib or Xalkori after FDA approval in 2011).
2 years ago, June 2012, I was admitted to emergency with severe abdominal pain, excruciating pain on my right side. I complained about "kidney stone" hitting me again;
In 2005, I went to emergency 3 times, complaining about back-breaking "kidney stone" pain, found no stone nor diamond but was eventually given the diagnosis of "solid pulmonary nodule", which later turned out to be lung cancer;
So this time, going in as a terminal cancer patient, I was not surprised to learn of my "diagnosis" - lung cancer metastasis to kidney and ureter causing blockage and end-stage hydronephrosis 转移肺癌引起的肾水肿.
After enough morphine pumped into my body, I was given a very long urinary stent, which went through (or bypass) my ureter all the way up to my right kidney. My urologist vividly described his work afterwards. He said he felt the resistance to the stent going up my ureter and into my kidney, as he believed my right-side plumbing was full of cancer sludge. The stent relieved me of acute kidney pain caused by hydronephrotic pressure, but I did not like it at all because my body didn't feel like my own. Less than a week later I went back requesting the stent be taken out. Dr urologist thought I was making suicide moves but he did it for me anyway. My real reason - I booked trip to Orlando couple months earlier and was due to drive down in a few days. I was not canceling the trip, especially when I was in trouble.
Just to be on the safer side, I went to another urologist at another hospital. She said - "I have seen many patients of different types of cancers developing hydronephrosis in their final days, and I can tell you it is a rather less painful way to die.", and she offered me an alternative to the "inside" stent solution - open a small hole on my side and connect an outside urine bag directly to my kidney!!! I imagined myself with my son's hand on left and my daughter's on right needing a 3rd hand holding my urine bag hopping lines at Disney world, for a few second, said no. Even I, most terminal of the terminal community, prefered living over dying.
I drove down to Orlando the following week, 16 hours non-stop (got about 4 hours relief from my co-pilot). I survived on copious amount of diluted cranberry juice in Orlando. A week later after long driving home, I was about the least exhausted of the gang of 8 - they were all asleep.
Then I went to see my urologist #3. He said, "your PET scan looks like atomic bomb exploded on your right kidney - but wait a minute, does that mean you have huge huge cancer in your kidney?" "Hmmm, ..." I thought for a minute. "that's the 18-FDG suppose to get flushed down the drain but did not because I had blockage in my ureter, not 18-FDG sucked in by metastasized cancer in my kidney! " Oh man, how stupid was I, and stupider was my other urologists!!! Brothers and sisters, listen, at occassions the stupidest human beings on earth are actually, some US medical doctors. I am Simon and I said so.
But, whatever that plugged my ureter - was it cancer? I discussed that with Dr F but could not reach a conclusion. Problem was - Xalkori the anti-cancer drug, or possibly other meds that I took, could have caused the kidney and ureter blockade in the first place, as I reasoned.
Xalkori was the 1st approved drug for ALK+ lung cancer, it's a very effective anti-cancer drug taken by mouth and does not have the usual & grave side effects of traditional chemotherapy. However, it has lots of side effects, and particularly delayed dynamic accumulative side effects. At the end of 2011 after more than a year on this drug, I have gotten used to things like strange taste in my mouth, ultra-sensitive odor sensing ability in my nose, floating light waves in my eyes, etc, but instead I had developed some more bothering known drug-induced problems, including, leg edema 两腿水肿, slower heart rate 心跳减慢, hormonal disturbance 激素短缺 (my testosterone was as high as some woman at the end of my clinical trial with xalkori - in other word, I was chemically castrated). With best reasoning, I regarded xalkori as fairly likely cause of my kidney problem, although kidney side effect has never been reported officially.
The discovery of ALK gene fusion/ rearrangement as gene driver for NSC lung cancer by Japanese scientists was published first in 2007, and the first experimental drug against the ALK gene target entered into human trial in 2009, and lightening-fastly in 2011 the Pfizer drug received expadiated FDA approval. This quantum-leap in drug development left some serious problems. We just don't know how bad and unsafe this drug can really be, both short and long term. A young friend's 57-yo dad suddenly died last year after a couple weeks taking Xalkori, the medicine I recommended to him - guilty me again (Z Li, my friend, I am sorry). I then learned that fatal ILD (interstitial lung disease or interstitial pneumonitis) had been reported in 1-2.5% of patients during xalkori clinical trial, in Japan and the US. But doctors never talked about such things. Very likely they did not even know. The drug company is unwilling to put any warning label on the drug, understandably. My Colorado superdoc, the one who first started the human trial of xalkori and is the chief hero of Pfizer's lung cancer success, told me Pfzier gave him deaf ears to his request to warn patients about heart harm problem or male menopause side effect.
The worst problem for patients on Xalkori - life-threatening brain metastasis. Xalkori, not a very large molecule, but has very poor ability to cross the BBB (脑血屏障). Couple weeks after returning from Orlando, I had an MRI scan of my head. The biggest tumor among several dozen had grown to 2.0cm, doubled in size from about 6 months ago, and tripled from when I started the trial. Fortunately my vital functions were all OK, despite having numerous tumors in my brain. My brain tumors did not grow much in the first year of the trial, most likely because I took the painless but brutal WBR (whole brain radiation) before the trial, NOT because xalkori had the ability to control brain metastasis. Note - If I forget anyone's name, blame WBR.
My youngest was only 1.5 then, so I had to stay on a bit longer. I started searching for newer and better experimental ALK inhibitors and found two 2nd-gen candidates both in phase 1 trial at two places - LDK378 or AP26113, at either Boston or Denver. LDK378 trial started a few months earlier and was the most recommended for me. However, after checking with both sites, I was told I had to wait for opening slot in the trial as all open slots were already taken. I could not afford to wait. I took AP26113 and I choose Denver over Boston, not because Denver was any better but it's much closer, relatively - it's ONLY 14 hours one-way by driving (I had done it 4 times) and 7 hours one-way door-to-door by flying. Traveling to and from Boston, could be nightmare, as I found out much later.
I had another problem. Turning the clock back two years - I initially signed up for PF-02341066 (Xalkori) clinical trial in Chicago with Dr Salgia, very nice guy. My local doctor in St Louis must have done a huge favor for me back then in 2010. He notified me that I did not have to go to Chicago just before I started the trial. The same trial indeed just opened in St Louis in time!
At the end of my xalkori trial in June 2012, I had cancerous lymph nodes cut out from my under arm for cancer gene analysis, at the newly formed "molecular genomics laboratory" at Washington University deparment of pathology. My doctor was highly excited about making future breakthroughs and betted heavily on cancer tissues harvested from my body. He told me that he will create new NIH clinical trial for me if the NGS analysis turned good results.
Indeed as he predicted - shortly afterward he told me they had found some "alterations" in my RET gene. As a former WU staff scientist myself I kept reading MedLine all the time, and was aware that RET gene FUSION was indeed the newly discovered oncogenic driver in NSC lung cancer, besides the known EGFR gene mutations and ALK gene fusion. So my cancer must have evolved from ALK positive to either RET positive, or ALK/RET dual positive. I immediately went into action, calling friends in India, and relatives in China, asking for help to buy an anti-RET cancer drug named Sutent. The drug was approved for use in kidney cancer in the US, but I would not be able to get it here because even if doctor prescribed it, I would have no chance to get insurance to pay the astronomical price.
Problem came when I asked for a copy of the gene analysis result. "Not ready" was the answer for almost 3 months! Long story short - later I found out, they detected a RET gene G691S variant in all my samples including my healthy tissues. This G691S gene variant is present in 15% of the world population, and it is definitely absolutely unquestionably NOT the lung cancer causing RET gene fusion as mentioned above. For those of you with some genetics knowledge, this G691S is a germline gene variant (present in every cell of the entire body), whereas the lung cancer causing RET oncogene is a somatic rearrangement (occurs only in cancer cells). I wondered if my world-famous doctor had ever finished middle school science in India. Of couse, much later I learned that he indeed had "created" a clinical trial using Sutent to treat all kinds of lung cancer, long before he "found" RET gene "mutations" in my cancer.
Not a problem, I haven't paid for made-in-asia Sutent, and I still had time to take the 2nd-gen ALKi trial in Denver. But a problem - I had to submit recent biopsy sample to qualify for the trial, so I went to WashU pathology to request my tumor specimens be sent to Denver.
About a month later in Denver, ready to start AP26113 trial, I learned from my UCH (University of Colorado Hospital) doctor that they were still missing my tissues. I contacted WashU pathology immediately. "All your tissues was signed out by someone and is overdue for return back to pathology". OMG, they were still making "breakthroughs" on my tissues, and they disregarded repeated phone calls from my Denver doctor to their offices requesting biopsy samples! I had recent surgery to removed all my cancerous lymph nodes and I did not have any more harvestable cancer inside me. Cancer tumors in my brain or near my heart were not really harvestable before i die, so what could I do? My messages to WashU chancellor and dean of med school started with, "First do no harm, ..."
On October 1 2012, I had my first PET and MRI scans after being on AP26113 for 8 weeks. "We have a complete response!" That was the first thing my Denver doctor said to me when he came in. The several-dozen-strong tumors inside my brain, were basically gone, and my chest looked much cleaner than before, and no more fires on my kidney.
Today 22 months into my AP26113 trial, I still have many holes inside my brain, but no or very little cancer up there. Praise the Lord. My body elsewhere restarted to produce tumors since late last year and tumors have been harvested twice already. There will likely be lung cancer cell-line(s) originated from me, immortal cells lasting thousand years for research purpose. After all, isn't that NIH clinical trials are really for - the betterment of human kind through research? I was reminded each time before going into surgery room - "the research work that will be done on harvested tissue likely will take many months or years and yourself will not likely to benefit from this." Even so, I have to pay for travel myself and I gladly did, even first class if I had to.
The road to self-preservation has never been smooth, especially when I looked back. Many a occassion, I was saved by an invisible hand from above. For example, had I been given an opportunity to take part in the LDK378 (FDA approved a month ago, new name ceritinib/ Zykadia) trial, very likely I would not have survived this long. It turned out, anti-cancer effect being on par with or slightly less than AP26113, LDK378 has much greater liver toxicity than AP26113, especially significant in asian population. I am very hopeful by the time AP26113 completely stopped working on my cancer, I will still have chance to move onto "3rd-gen" ALK inhibitor, with relatively well preserved liver and kidney function. That would be very difficult if not impossible had I taken LDK378. Praise again.
Back to Jenny, I only learned this week, that she had complained on Inspire.com recently about "dark urine". My guess is that she had serious problem in or around her kidney, and that was likely from some un-identified side effects of Xalkori. I feel really sorry I have not been paying much attention on Inspire lately. Now it's too late. I should have shared my experience, good bad and ugly, earlier. For some, you know I am a heavily burdened, but even more heavily blessed, man (or woman?).
Another thing I know about Jenny is that she had openly welcomed the coming of her end on earth. I had guessed she was a christian but she did not reveal. Now I know. Here is the page -
选择“Disable on www.wenxuecity.com”
选择“don't run on pages on this domain”
