I’ve never been much into games, but this I’m willing to do! Diversion and distraction can be a wonderful thing when one is ill. I wish I’d found this during the interminable days in the hospital!
It’s 5 days since my first infusion of MK-3475, Merck’s anti-PD1 immunotherapy drug, in clinical trials for non-small cell lung cancer and melanoma. It’s been fast-tracked by the FDA for melanoma, so if the data is smashing, it could be approved very quickly (for melanoma). While I think it’s a good thing that three large pharma companies are racing to be first to market with their anti-PD1 or PDL-1 drug, I hope safety and thoroughness aren’t being sacrificed. We all know that many long-term side effects can’t be discovered until way down the road, but I wonder if there aren’t markers early on to point to possible problems.
I’m vigilant as regards pneumonitis. I’m already short of breath, and it has not improved, which worries me. Of course I have a couple of pulmonary embolisms… I really just wish I could know sooner rather than later if this is going to work. No such luck, I’m told. One just can’t know if it’s working or not, at least not right away.
I’m exhausted. Seriously, like run over by a Mack truck and beat with a baseball bat. I can sleep standing up, it’s that bad. The night after infusion I had severe chills and my already off-the-scale pain escalated into the stratosphere. Today is the first day I’ve had any relief – I’ve increased my morphine dose by half and am now taking percocet simultaneously (there is no such thing as breakthrough pain – I’m already there, all the time). Worse pain? Apparently things could get worse before they improve – inflammatory response and all that. I’ve heard others are also experiencing increased pain… and itching. Yeah, more itching all over. So I can’t get comfortable, as sleeping on any part of my body for over 4 hours produces excruciating pain in that area – heating pad, pain patches, cushions, etc. notwithstanding. I haven’t had an unbroken night’s sleep yet. I sound like a mental case.
Thankfully, cannabinoids are allowed. Hurray, cannabis isn’t illicit! I just have to muster the energy to make something. Am working on that tonight. Topical application of cannabis-infused olive oil works fairly well, but is very temporary and I don’t have much of it. I’ll have to source it in larger quantities to be able to use it as a massage oil. Also helps the itching. So that’s immunotherapy so far.
Meanwhile, the Christmas season, like sand, is sifting through my fingers. Time just laughs at me. Energy laughs harder. They conspire to keep my eyes from being open long enough to accomplish anything as seasonal as sending cards or shopping for gifts or even making food. Resistance is futile, I should just give in.
So, edibles recipes. I’m thinking shortbread.
This may become a rambling, stream of consciousness, meandering post. I’m writing on my phone as I descend into the mists and hollows of painkillerville, from a hospital bed in a room with a view which i now can see only because my roomie checked out. I’m on the far side of the room, with a lovely view of the hallway. This is my first hospitalization ever. I’ve landed here due to – surprise – pulmonary embolism, aka blood clots in my lungs. No surprise actually, it’s somewhat inevitable, but I’m still disappointed. Lung cancer patients have something like a 70% greater risk of getting them than other high-risk folks, including cardiac patients with leaky heart valves, though maybe not post-orthopedic surgery patients. Cancers secrete many pro-inflammatory substances, among them pro-coagulants, hence the high risk for blood clots.
Staying active and hydrated, taking aspirin, wearing compression socks when traveling, etc all contribute to preventing clotting events. However, at some point it seems bound to happen, especially to those with advanced disease and, I suspect, who are heavily pre-treated.
I’d been feeling lackluster, experiencing more shortness of breath (SOB) than usual, but recovery was quick and I chalked it up to progression. Being winded by the routine airport traverse of parking lot-ticket counter-security – boarding gate was a surprise/disappointment but the general conclusion was that I probably wasn’t quite healthy enough to go Nashville. I went anyway and it was alright, except for the two arctic storms which rolled in back to back the last day there. Anyway, lack of stamina and low energy levels exacerbated by an ill-suited travel companion amplified my awareness that I was heading downhill fast and maybe should’ve stayed home in favor of completing clinical trial screening procedures in order to begin treatment a week sooner. Brilliant, Captain Hindsight!
I went to ucla for a battery of tests on the 9th. A looong day without pain meds, capped by a 3-hour drive home. I popped pills, went to bed, disregarded phone calls that came in at 9pm. Turned out to be the UCLA doc, calling about the blood clots. Thankfully he emailed. Per Murphy’s Law my printer was on the blink and Hub, having now caught the flu from being run down, drank NyQuil and crashed while I was almost in tears trying to print the scan report and figure out who could go to the ER with me. It was almost midnight on a Monday night. He angrily got dressed, slugged down a shot of espresso and brought me. Thanks to technology I was able to email the report to the ER doc. A resident came and did her assessment, wrote it up and her supervising doc seems to have approved it. I got in at 12:15 and by 4am I was barely moved to a hospital bed. Once settled in I sent Hubs home – he looked miserable and felt worse, I’m sure. The orders were released around 5 and I finally received my first shot of Lovenox, a warfarin-free “blood thinner”, along with some morphine and all the usual pills I take. I badly wanted to sleep but it was not to be. Between breakfast and what seemed like an endless parade of people taking vitals, then blood, asking questions, checking my skin, etc. I was convinced there was a conspiracy to keep me from sleeping. I will say, however, that the nursing care was cheerful and efficient, and the food not bad. Eventually I just passed out until another resident came in… who was the antithesis of the ER resident (who only wanted to follow the UCLA onc’s orders) and was obsessed with defying the orders. I was so annoyed but had confidence that my local oncologist would do the right thing. And he did.
I’m home now (got home Wednesday night). I now have to shoot up Lovenox twice a day until the pharmacy gets in a supply of Xarelto, an oral, non-warfarin blood thinner. I have friends who inject themselves with insulin every day, so I won’t complain. I have bruise dots at all my injection sites, but mostly I have to remember that I’ll bruise and bleed easier, and will take longer to clot, and must be very careful of injuries. I’m just glad I have this option, which is a much costlier one than Coumadin, but superior for lung cancer. The other choices are Arixtra and Eliquis. I’ve not done the research to know the difference, but I’ve always been clear on the fact that Coumadin is not a good choice for lung cancer, that Lovenox or similar is always indicated. I’m grateful for not having to argue with the internal medicine resident – I just couldn’t understand her resistance to alternatives and her obsession with using warfarin. And I’ve just heard that it takes months – MONTHS! – for pulmonary embolisms to resolve!! So I’m still in danger?!! I feel much better today, having more energy than I’ve had in a month, it seems. Maybe a product of getting enough sleep, or of needing to care for a sick Hubby. Hmmm.
I’m now off Tarceva (TK inhibitor/chemo pill), being in the (scary) wash-out period prior to treatment. I start the trial on Tuesday, 12/17 at UCLA in Santa Monica. Hubs won’t be with me, so it’s daunting. The infusion is 30 minutes, after which I hope to stay the night at a friend’s house since I have to return for bloodwork late the following day. I imagine I’ll have to stay the second night too, as I’ll once again be in rush hour traffic. I hear side effects don’t happen right away, which isn’t heartening, as he may still be away when they kick in. I may have to lean on people, which is rough, it being the holidays and all.
Speaking of holidays… all the days between Thanksgiving and Christmas seem to sifting away like sand. I was hoping for a different holiday season than the past few years, but it doesn’t appear to be so. Looks like another non-decorated Christmas, mostly because of all the activity and the lack of manpower to put and take down decorations. Oh well…
I’ve blown it by not posting the past three days but I feel adjudicated by reading The Cuckoo’s Calling by Robert Galbraith (JK Rowling’s alias). I’m not finished but it’s an enjoyable read. Lots of explanatory stuff, very little action. I’ve not felt great, which I’m trying to get over by Thanksgiving. Good and bad days are unpredictable, in spite of the painkillers, heated blankets, sunny days. Acupuncture helps a bit, but the current set-up makes it difficult to receive the amount of treatment needed to establish pain control. With me it’s an evolving and complicated game of whack-a-mole for which consistency is critical. Alas, I’ll deal with what I have and hope for better days soon. I’ve got 5 acupuncture seeds in each ear and 3 on my right hand fingers to help with my breathing and skin toxicity. I need about 20 more for bone pain…
The biopsy results are in… my tumor tissue (from the collapsed left lung, no less) is PDL1 positive! Whether this is a result of chemo or Merck’s different assay (as opposed to Genentech’s), I hope it’s predictive for my response. A few more screening tests and with any luck at all I can start the trial.
The biopsy was a feat of efficiency, done at Ronald Reagan UCLA Hospital in Westwood (LA). From the valet to the cafeteria, I was impressed by the precision of the hospital’s well-oiled machinery. My nurse from Yorkshire (Leeds, specifically), England chatted cheerfully about her travels, set me up on the CT scanner bed, and injected a cocktail of morphine and Versed (midalozam) into my IV. I don’t know if the amount was insufficient or the lidocaine applied topically to my chest hadn’t taken effect, but I definitely felt the stab through my lung when it came. Yep, I surely did. The resident who performed the procedure (a handsome young guy named Dr. McGraw) told me to take a breath, hold it, then plunged the giant needle in my chest (through the front, Pulp Fiction style). Once the thing was in he left it there, intermittently dropping tubes for samples. (Hubs says it’s much like drilling for core samples, though with more primitive implements) He clipped away as if he were pruning roses. I wanted him to start whistling but he didn’t. Then it was over. I was alert and ravenous, eating ancient flight pretzels from the bottom of my backpack, orange slice candy, whatever I could get my hands on. The doc came in to check on me, shoved a heated blanket roll under my back to keep me on my side and said an x-ray wouldn’t be done since, well, the lung was already collapsed. We chatted a bit about the difference between PD1 and PDL-1 inhibitors, what was edible at the cafeteria, then he wished me luck and for all I know went back to his office for Playstation.
Now that I’ve cleared that hurdle I’m faced with a bit of dilemma. A slot in the (Clovis) CO-1686 trial – the one I’ve been waiting over a year for – may open up in the next two weeks. It’s still in Phase 1 dose escalation, but it’s so close that I’d rather risk getting on now rather than continue waiting till it reaches Phase II. As I’ve mentioned before, I believe my chances of response to that drug are much greater than to the Merck Anti-PD1 agent – which is the clinical trial I’m about to embark upon. I’m in a quandary, because starting the Merck trial would prevent me from the Clovis trial for now, and possibility of response is only 24%. BUT, response could be durable, lasting over a year. There are also scary side effects, whereas the Clovis drug has mild to none. The duration of response to CO-1686 is in the range of 6-10 months but it’s a blissful, if short period, I hear. I’m torn.
Hubs has a business trip to Nashville and I may join him. If I don’t make it to the end of the year at least I can say I went on one trip in 2013. For now I’ll focus on giving thanks for a good run, and remember my Dad, who passed away exactly 6 months ago on the 28th. I’ll light a candle for the fallen, say a prayer for the lost, and rally the universe for grace to blanket each one of us. May we transcend the darkness, each in our own way.
Love to all.
Gorgeous autumn day. Too bad I can’t go for a walk. I’ve a PET scan tomorrow – out in Indian Wells, a desert community about 1.5 hours away (past Palm Springs and Palm Desert). Why Timbuktu instead of the local Kaiser? I saw the “new” onc in Palm Desert again last week, and he placed the authorization – I’m guessing it automatically stays within the local service area if he doesn’t manually enter another facility. I went ahead and scheduled it in the interest of expediency, and it’s kind of a nice drive in the winter. It’s a waste of gas, but better to get it over with. He also made orders to receive cisplatin-vinorelbine (Navelbine), which I discovered requires a central line or port to be placed as infusion is weekly and…takes 7 hours. That’s right, 7 hours. Maybe it’s the cisplatin – it requires hydration before and after. But having a central line means a catheter hanging out of my chest, which I have to flush twice a day. A pain in the ass and yet another risk of infection. Who needs that? Apparently Navelbine burns the skin so a catheter is preferred. The UCLA doc says they infuse it without a central line, but for a weekly infusion it’s understandable. I scheduled placement of the catheter for Thursday and chemo for Friday… and just now canceled the whole kit and caboodle.
These days, everything is in the interest of time, regardless of some other difficulty or inconvenience. Saw Dr. Goldman at UCLAfor the 2nd time on Monday (4th). My brain was a bit scrambled from Carlsbad Girls’ Weekend, but again, I grabbed the soonest appointment available. My opinion of him hasn’t changed from the first. We don’t click, but I’ll give him a chance. Having never met Dr. Garon but hearing him online and having the Matsunobus’ recommendation, he seems a better fit. For the immediate future, it might be fine to stay the course, since Dr. Camidge referred me to Goldman, and his current plan is okay.
The current plan: Enroll in the Merck Anti-PD1 trial ( agent nameMK-3475/Lambrolizumab) at UCLA, even though it’s available at A. “Merck pays for everything, you don’t even need a Kaiser referral. They will pay for the biopsy; it’ll be done here (at UCLA)”. Adequate tissue will be collected to enable testing of PDL-1 for trial eligibility. If it returns negative, the remaining tissue can be used for the Clovis trial (CO-1686). My slot in that trial is not with the group that starts the end of November, it’s with the group after that, so mid-December. I assume the biopsy will make the enrollment timeline.
I mentioned the bump in my arm to Dr. Jang and he thought it was the ideal possible biopsy site. Dr. Goldman palpated it and said it’s very rare to have metastasis beyond the elbows and knees. If it lights up on the PET scan, they’ll do an ultrasound-guided biopsy, but he was skeptical. Otherwise he thinks it might be easy enough to biopsy the collapsed left lung. I call that “stabbing in the dark”, but what do I know? I pointed out that I had a small met on the right adrenal which appeared in the January PET scan, but it hasn’t been mentioned in any scans since.
If the tissue returns PDL-1 positive, I could start the trial, but it’s 9 weeks before the first confirmatory scan. Participants are randomized to infusion every 2 or 3 weeks. I know 2 people who discontinued and 2 who’ve died – it didn’t work quickly enough or they developed severe complications? If I start the trial and am consequently offered the CO-1686 and skip out, I would later be disqualified from trying other Anti-PD1 trials (which makes staying long enough to see if it works kind of mandatory, but may result in losing my place on the CO-1686 trial). If anti-PD1 works, I could blow off CO-1686 altogether and hope the AZD9291 trial is available at that time. Ideally CO-1686 will become available before I start, or after I’ve determined MK-3475 isn’t working.
How they compare: Response rate: better with CO-1686 – 70%, only 25% with MK-3475. Duration of response: If MK-3475 works, response could be durable to a year; only 6-10 months before resistance with CO-1686, although it’s possible the addition of MK-2206 (an AKT inhibitor I tried at UC Davis in 2011) overcomes resistance and prolongs duration. Side effects: CO-1686 wins with no side effects (some muscle ache, I’ve heard); MK-3475 has pneumonitis, colitis (hence diarrhea, etc), rash, pruritis, itching, fatigue…scary stuff, really.
Ideally, the path should go like this: CO-1686 ===>Anti-PDL-1/PD-1 inhibitor ===> AZD9291 ===> addition of 2nd targeted therapy to overcome resistance ===> 3rd generation inhibitor or back to chemo/inhibitor combo (Alimta+Tarceva).
We discussed how I’m doing and I admitted to excruciating pain while still being able to walk 4 miles. I’m really not coughing, but my chest feels tight and not quite clear (my O2 was 100% though). When I bring up how far out I am from chemo (6 months next week), he said, “Stop thinking about that.” He seemed irritated but in classic guy fashion, didn’t clarify – perhaps it should be obvious. Some people need confirmation, however. He might’ve said, Look at it this way: 4 cycles of chemo and continued Tarceva has held you this long – the longer the better – instead of worrying about how long it’s been, rejoice and hope for longer control. Tarceva is probably still effective to some degree and things look stable. So why am I in so much pain? It’s the bones. My point is: our technology isn’t good enough to detect small movements, but our bodies are quick to recognize when things are going south. The scans may say stable but the pain says otherwise.
This week: PET scan, Zometa infusion, wait for rebiopsy appointment at UCLA, they will request my 2011 tissue and have it tested by Merck (will probably be negative for PDL-1), wait for test results from rebiopsy, proceed to a decision. Goldman thinks I ‘ll be okay for the month it’ll take to arrive at the next course of action. Hubs points out that there are a hundred others rolling in on wheelchairs and oxygen tanks and compared to them, I’m just being dramatic. He agrees with Goldman that I over-analyze.
As a sidenote, I’ve now tested cannabutter blondies for a week. The conclusion: PROS: great for pain control, appetite enhancement, awesome for sleep, decent for nausea control, average for creativity. CONS: not great for driving, energetic activities, or actions that require cognitive alertness and memory; coming down necessitates a nap, can kill motivation. Overall, I prefer to use it over narcotic painkillers, but here’s the question: will edibles disqualify me from clinical trials? An exclusion criteria is “Continued use of illicit substances.” The blood test may isolate THC – not sure it’s medically established yet as not “illicit”. On the other hand, there’s Marinol and Sativex by prescription, so maybe it is.
That’s the glazed-eyewitness news for now!
…for putting your brave face to lung cancer, for calling it like it is, for loving life and having the courage and fortitude to attempt and withstand grueling experimental treatments in the pursuit of time. I and the lung cancer community salute you and your dancing!
It’s time to play Find the Next Rock to Hop On again. After three months of feeling better than I’ve felt in a year, the August CT scan showed a 1.9cm ground glass opacity (in my only lung). Clearly Tarceva the 3rd time around isn’t keeping the bulls in the pen. I’m now almost 5 months out from the last carboplatin-gemcitabine infusion (May). I’ve tried to get my oncologist to order a round of chemo, but she probably thought things would move more quickly. Sadly, pain level has escalated from 1 to 8/10 in a month. I believe radiation to my bone mets would bring relief, but will it extend my survival or weaken me further?
Genentech sponsors a Phase II trial of an Anti-PDL1 agent (explanation of mechanism of action here) which I’m interested in. Immunotherapy has been the star of the last two ASCO conferences, so it’s got buzz and bucks to back it up. The preference for Genentech’s agent over the more well-known Anti-PD1 agents Nivolumab (BMS, fast-tracked in some cancers) and Lambrolizumab (Merck, fast-tracked in melanoma) is that it doesn’t carry the pneumonitis side effect. Important when one only has one lung. I managed to line up my ducks, order 15 unstained slides from my 2011 biopsy, drive to the pain-in-the-ass location on Wilshire to be evaluated, but dagnammit – the tissue tested negative for PDL-1 expression (must be positive to enroll in the Phase 2 study). I’ve just had chemotherapy, which induces expression of PDL-1 on the tumor’s surface, but this means I need a new biopsy to retest. I would’ve had to get one anyway, but now I really have to have one, so I can have enough tissue to test for cMET (another possible course for targeted treatment) and for the Merck Anti-PD1 trial (I don’t really want to do that trial, but there aren’t many options left) as well.
My preference and hope was to get on a trial for CO-1686, a third generation TK inhibitor effective against the T790 mutation (acquired from all these years of being on Tarceva!). There’s confirmation of its lack of side effects, which would be a relief after years of torture. Clovis reformulated CO-1686 into a hydrobromide salt tablet, and now the trial is in suspended animation while all current participants are stabilized. Word on the street is Q1 2014 before anyone new gets invited into the club. What’s a girl to do (to stay alive) for 4 months?
There are a couple other possibilities, but they’re not options unless my tissue expresses the particular genetic aberration. The two leading Phase 2 options are cMET inhibitors (one MAb – LY2875358 @UCLA, the other a small molecule – Cabozantinib or XL-184 @ USC or City of Hope). Other Phase 1 options include DS-2248, a Heat Shock Protein 90 inhibitor (available at Loma Linda and UC Irvine), LY2835219, a CDK4/6 inhibitor (I know nothing about this type of agent), and AMG337, another MET inhibitor. This is all very technical, but stating it here is like talking to myself, sorting it out, trying to see if I’m lucid in my evaluation of the situation. My eyes are glazed over too…
Getting into trials is an intricate, stressful, strategic process. Time passes, symptoms escalate, doctors don’t seem to notice or care, trial coordinators don’t return calls – it’s maddening. Options are limited by several factors, one of which, ironically, is the length of my survival. Because I’ve survived so long, I’ve had too many lines of treatment. Most trials exclude those who’ve had more than two lines of chemotherapy, 1 EGFR TK inhibitor, 1 MAb (monoclonal antibody), or those who don’t test positive for the required mutation, protein/gene expression, etc. And of course there’s the logistics of location/travel, insurance, timing – all heaped on a patient already debilitated by disease and treatment. Jumping through hoops is a true idiom for this situation. For me, the hoops are ever decreasing in size while increasing in number.Cosmic convergence has to happen for things to go just right, and having an aggressive oncologist helps quite a bit. My oncologist is a nice person but inexperienced with aggressive, cutting edge treatment. I wonder if I shouldn’t see another oncologist in the same practice – someone recommended by the clinical trial nurse in Northern Cal?
So, what did I do this summer? Not much. Went to Pismo Beach and Hearst Castle while the inlaws visited. Enjoyed the America’s Cup races in SF, partied with Hub’s kiwi friend/ex-boss. Quite a large kiwi contingency out for the event! Hubs is completely immersed in riding quads and traveling for work. I was, for a moment, fantasizing about having a blockbuster response to immunotherapy and taking up stand-up paddle boarding. I’m still hopeful but I got my reality check when the pain re-declared itself. I’d started making plans for fall but I’ve pulled back and cleared the slate, anticipating treatment.
I’m reading Joan Didion and hoping I make it to year’s end!
It’s been here, actually, but today it’s 84 degrees (fahrenheit, or 30 celsius roughly). Trees are in bloom, the first tomato is in the ground! I wish it could stay this way. The hubs has embarked upon version 2 of diy pool-heating, with the hopes of swimming by the end of March.
We are hosting Hub’s colleague from the Netherlands. It’s a business visit, and I’m afraid I’m not being much of a hostess. We both clean up, but there’re always details that amount to quite a bit of work. I have, however, reached the point of not caring. I’m in so much pain and feel so crappy, I just don’t care anymore. I’m wearing sweats and a camo bandana on my head. I look horrific but don’t have the energy to give a damn. Our visitor/friend has seen me pre-cancer and in my bloated Alimta days, so he knows what I used to look like. He smokes, of course. Thankfully, the weather has allowed them to spend most of the time outside, talking business in shorts and flip flops.
I have to cook tonight. There aren’t many decent places to eat nearby, and by dinner time the guys have had a few drinks. Which means I have to drive. There’s no food delivery either, except pizza. It was wretched (we haven’t found any pizza around that we like, except a place that doesn’t deliver), and I was sort of embarrassed. That’s the third time I’ve taken company out to eat and been embarrassed. Not good. Will have to go farther afield.
Having guests stay over is incredibly tiring under normal circumstances. In my condition, it wipes me out. It’s obviously not a great time to be doing it, but since it’s business, I had to concede. I’m hoping they go to the Bay Area tomorrow. If things go well, Hubs may actually be able to work in the area and not have to live in another country to work. Either way, I’m anxious to get on a clinical trial and stabilize for a bit. I’ve never felt so bad in 7 years! Ugh.
There’s fear that chemo’s not doing the trick, as my pain level hasn’t decreased at all. It’s possible any response would take longer due to my extensive pre-treatment. I’m undecided as to whether to continue Tarceva and continue platinum at the same time. The discussion with Dr. Camidge (Denver) was to do single agent Gemzar with Tarceva. The addition of platinum was an aggressive option which was to be dropped if intolerable. There was never any discussion of dropping Tarceva, especially in the setting of 5th or 6th-line treatment. So I’m considering doing one more cycle of platinum and maybe getting a scan, then continuing with Gemzar and Tarceva. The pain makes me feel pretty bad, but the combination of pain/coughing and crappy chemo (and painkiller) side effects is unlike anything I’ve experienced in all these years of treatment. I think I’m being optimistic and thinking that’s why I feel so bad, and not because disease is taking over my body. Some days I feel like I’m not getting enough oxygen.
So I’m thinking – scan, drain pleural effusion if I have one, drop the platinum, go to UCLA for consult to hold spot on waiting list. That’s the plan…
On the bright side, the gift goddess has visited two days in a row! First, a lovely package from my cousin (a breast cancer survivor still on Herceptin) containing five books of poetry (Keats, Byron, Tennyson, Donne, and Frost), organic lollipops, a beautiful mug, mango green tea, and french butter cookies! Then, from our client/friends in NZ, Laguiole flatware! I’m beside myself with delight 🙂 So please, karma gods – please bring me another package – you know the one – the one marked “Fragile – contains More Time”… If we’re going to get into wishful thinking, might as well dream big…