Tag Archives: HSP-90

Next steps

Where to start?  It’s been a busy week.  On Thursday I went to Boston for allergy testing. I sleep on a natural latex mattress and had been using a pillow out of the same material. Several mornings in a row I awakened with a lot of swelling around my eyes and cheeks. After spending the night at a friend’s home and waking up minus the swelling, I returned to my own bed only to have it happen again. I replaced the pillow with one that wasn’t latex and  voila, no more swelling. Because I am in and out of a hospital so much, there was a chance that I had developed an allergy to latex. A prick test (yes, that’s what they call it) came back negative and I am awaiting a blood test, but it seems unlikely that my facial edema was related to latex. A minor medical mystery.

On Saturday, we had a belated birthday party for Peter, who turned thirteen in April. Seven of his buddies spent twenty four hours at our house. The air was thick with adolescent testosterone. When they weren’t eating they were out in the woods using each other as target practice with a battery of air soft guns. They all had on protective gear and were instructed to not shoot each other in the face and/or point blank, and, for the most part, they complied.

The entire air soft concept took me awhile to warm to. Despite my own access to not only cap guns (remember the smell of a freshly detonated cap?) but twenty two rifles as a child, as an adult and a pacifist, I have a general policy against weapons of any sort. Not easily thwarted,  a then-three-year-old August would chew his toast into the shape of a gun. Gradually I acknowledged that an attraction to things that shoot was somewhat intrinsic, and rather than banning firearms, I did my best to stress respect for life while allowing for fantasy play. These new guns do take it to another level. However, the boys had a great time and we all survived.

Sunday afternoon we partook of a more gentile activity, as Peter had a music recital. It was lovely to listen to a wide range of ages and abilities on a variety of instruments, including Peter Duff on guitar.

I turned in early that night, exhausted from the boy party, a big boy party (remember Go Dog Go and “a dog party, a big dog party”; I cut my reading teeth on that book). Yesterday morning I left the house at six a.m. to follow that familiar path down the highway to Boston. All the trees are almost completely leafed out now, and everything is so green. There was also a lot of roadkill. I saw opossum, fisher cat, coyote, deer, as well as some mangled black fur of unknown origin. It is a sad rite of spring;  young animals unaware of the great danger that crossing a highway poses.

At my  appointment, Alice (Dr. Shaw) laid out my treatment options in more detail. My next scan is in three weeks, and will help us to assess how quickly the cancer is developing. At some point I will need to undergo another biopsy, in order to learn more about why I have become resistant to the 1066 as well as to determine what the most appropriate therapy might be. If the pleural effusion has gained in volume, some of the fluid could be removed and analyzed. The presence of the fluid makes it viable to remove ‘live’ cancerous cells that could then be cultured.  Clinically that would be a real advantage, but from a therapeutic perspective a pleural effusion can be difficult to manage, so I am hopeful that such a scenario is not an option.  In lieu of that, I would likely have a wedge resection via VATS, as a punch biopsy would not procure enough material.

As I mentioned before, a HSP-90 inhibitor might be the next logical step.  HSP-90 is an acronym for Heat Shock Protein 90.  In healthy cells, HSP-90 acts in part as a chaperone that shields proteins from destruction. In cancerous cells, a number of proteins can be over expressed and inhibition of HSP-90 may induce apoptosis (cell death) through inhibition of growth signaling pathways. A phase II trial for HSP-90 is now enrolling patients with ALK mutations at MGH.

Alimta remains a fallback possibility and we will be keeping our eyes on a couple of ALK inhibitors in the pipeline (in addition to Ariad, Novartis has one in development).  My fingers are crossed.

In a couple of weeks, ASCO will have it’s annual meeting and this year the PF-02341066 trial results will be presented in a plenary session.  I am interested in seeing the newly published data, including the actual number of participants who, like myself, have relapsed.  I am also happy that the resulting exposure and publicity will make so many more oncologists and patients aware that people with NSCLC should be tested for mutations. It really is the dawning of a new era in cancer treatment.

Glass slippers: finding one that fits

Spoiler alert:  For those of you who are currently enrolled in the PF-02341066 trial and/or considering enrolling, please do not be discouraged by today’s post.  The trial has been nothing short of miraculous for me and many others.  I have always known that it was, however, not a cure for me, but rather a much needed ‘vacation’ from my cancer.

Monday was the day of my appointments in Boston.  As I got dressed that morning, I contemplated fixing my little V pin to my shirt, in celebration of five years, but somehow it just didn’t feel right.

It’s generally a solo trip, but David came with me this time.  Due to the fact that it was Patriot’s Day, traffic was a breeze, and we got to the hospital with plenty of time to spare for a cup of coffee.  Dr. Shaw was prompt, and as she entered the exam room, I could sense that it wasn’t going to be good news.  Had it been a book that I was reading, I would have marked the page, shut it, and walked away. Maybe later.

Not a book though, but life as I’ve come to know it (quick fact:  as someone who is fifty and was diagnosed with cancer five years ago, I have now spent 10% of my life battling lung cancer).

So, cut to the chase, it is now apparent that my cancer is developing resistance to the PF-02341066.

There is no longer a single area of concern in my upper left lobe, but several, including one in my right lung.  In addition, the pleural effusion which had been stable for five years has gotten slightly larger.  I’ve scanned in a copy of the report:  for those who are curious, if you click on the image you can see it full size. Radiologist’s speak, and it’s a wordy one.  Quite the opposite of the ideal report, which would be short and sweet and use words like ‘unremarkable’.

As I left Alice’s (Dr. Shaw’s) office, I felt like Cinderella at the ball when the clock struck midnight.  I had been living in this fantasy which included a future and I was really getting used to it.  It hit me really, really hard.

However, after approximately 36 hours of feeling sorry for myself, I rallied.  This was due in no small part to the fact that Alice called not once, but twice with updates on potential avenues for treatment.  Once again we are at the very edge of what is available.  I was describing it to Peter as being similar to trying to cross a fast moving stream on a path of stones, and he more aptly envisioned the stones as the backs of turtles: they too are likely in motion.

So, I will stay on 1066 as long as I am able. Hopefully that will be for at least several more cycles. I would then potentially enroll in a trial for a HSP-90 inhibitor (HSP-90 is crucial to several proteins which stimulate growth in cancer cells). Alternately, I might return to a more traditional chemo such as Alimta. Some of the other options we had once talked about, including a wedge resection or radio ablation, are no longer viable, as my BAC appears to be multi-focal once again.

Perhaps most exciting, is a new ALK inhibitor by Ariad that was announced at the AACR meetings.  It is specifically tailored for ALK mutations that have become resistant to PF-1066, and it is reported to be even more potent.   However, it is preclinical:  not even in phase I yet.  One of those swimming turtles.

So, I’m shopping for just the right glass slippers again (or, back in line for another miracle).  And in the meantime, I’ve got to stay positive, be strong, get as much benefit out of each treatment as possible, and just hope that medical science is one step ahead of me.

Wish us all well.