Drugs 3: Vinblastine

Vinblastine is the agent in the ABVD regimen I feel as though I know the least about.  The other three drugs at least have one easy thing about them:  doxorubicin = heart, bleomycin = lungs, and for me, dacarbazine = pain.  I honestly don't even remember reading about vinblastine once in pharmacy school.  The other name for vinblastine is Velban and it is a plant alkaloid.  It is generic.


This little factoid comes from the package insert:

It is the salt of an alkaloid extracted from Vinca rosea Linn., a common flowering herb known as the periwinkle.

An even more interesting piece of history comes from wikipedia:

Vinblastine was first isolated by Robert Noble and Charles Thomas Beer from the Madagascar periwinkle plant. Vinblastine's utility as a chemotherapeutic agent was first discovered when it was crushed into a tea. Consumption of the tea led to a decreased number of white blood cells; therefore, it was hypothesized that vinblastine might be effective against cancers of the white blood cells such as lymphoma. 

It has an interesting looking molecular structure.

Like the others, vinblastine is an IV product, given as a short infusion rather than slow push.  It is a moderate vesicant.  My dose is 13.44mg IV every other week, or 6mg/m2.  

How does it work?  The package insert is not as clear as Lexi-Comp.  Using the latter resource:

Vinblastine binds to tubulin and inhibits microtubule formation, therefore, arresting the cell at metaphase by disrupting the formation of the mitotic spindle; it is specific for the M and S phases. Vinblastine may also interfere with nucleic acid and protein synthesis by blocking glutamic acid utilization.

In other words, it inhibits cell division by binding to the parts of the cell that push and pull chromosomes apart as daughter cells are about to split.  For those of you interested in pharmacology, the package insert has other interesting information on effect reversal. 

Vinblastine has low emetic potential (<10%).  It is known for its myelosuppressive properties, causing leukopenia and granulocytopenia (nadir: 5-10 days; recovery: 7-14 days).  Incidentally, this seems like an appropriate spot for a pictorial.  Here is a graph of my WBCs.

Any guesses when the chemotherapy started?    Vinblastine is contraindicated in "significant granulocytopenia."    

Other side effects include constipation, alopecia, bone and jaw pain, malaise, and hypertension.   More rare things include a host of GI effects including mucositis and a metallic taste.   It can cause paresthesias, photosensitivity, and rash.  Other curious things include SIADH, Raynaud's, and nystagmus. 

Otic side effects are even more curious to me, and Lexi lists the following:  Auditory damage, deafness, vestibular damage.  I have had, almost daily for weeks, that sensation where your ears need to be popped.  They don't pop, though, and simply pressing on them seems to cure the weird sensation.  (So if I have my hands over my ears near you, I'm not trying to be rude.) However, I've not noticed any balance issues.

Vinblastine is an interesting drug from a pharmacokinetic perspective.  Per the package insert, it has a triphasic serum decay pattern.   The terminal half life is 25 hours, therefore, it is about 4-5 days until it is nearly all gone.  It has a very large volume of distribution (27L/kg) and is extensively bound (99%).  

Vinblastine is also interesting metabolically:  Per Lexi, it is a substrate of cytochrome P450 isozymes 2D6, 3A4, and P-glycoprotein.  Meanwhile, it inhibits 2D6 and 3A4 while inducing PGP.  It is a weak inhibitor, however.  This can obviously lead various drug-drug interactions, and so, I decided to look at the interaction profile of my ABVD regimen.  Aprepitant (Emend) can actually boost the concentrations of adriamycin and vinblastine mildly.  Adriamycin and vinblastine are also PGP players, but since the drugs are not given orally and we are not aiming for the CNS, the interaction is only theoretical.  Bleomycin and dacarbazine show no interactions.  What else?  These chemos can decrease my zyrtec and increase my flonase.  No big deal.

What else is vinblastine used for?

Hodgkin's and non-Hodgkin's lymphoma, testicular cancer, breast cancer, mycosis fungoides, Kaposi's sarcoma, histiocytosis (Letterer-Siwe disease), choriocarcinoma,

 bladder cancer, melanoma, nonsmall cell lung cancer (NSCLC), ovarian cancer, and soft tissue sarcoma (desmoid tumors).

What else to say about vinblastine?  Package insert is here.  Chemocare website is here.  Lymphomainfo.net website here.

Chemotherapy (5 of 12): 2.5 of 6 cycles done

Wow.  Yesterday hit me hard.  I got a full 8 hours of sleep Sunday night, which is somewhat unusual for me.  I went in early to have my blood drawn peripherally, rather than through the port.  (Yes, this was my decision and oncology doesn't understand it).  Then I met with the oncologist and most of the discussion was dominated by talking about radiation oncology, and the new port.  This was actually fine, I couldn't think up anything else I wanted to know, short of whether or not I could now lift above my head with the new Bowflex, now that I have a port instead of a hohn.  (I cannot, btw).


So, on to chemo.  I had chemo through my new port, and that went fine.  I didn't get to eat before chemo and started getting sick. So Sarah ran to safeway for ginger ale and a sandwich.  She asked what I wanted and I decided on a prepackaged sandwich. I already hate ham and cheese, so I told her to go for that, since I knew I'd eventually not care for whatever I ate.  I took two bites, brushed up against a pickle (insta-hurl) and I was done.  made do with a small bag of cheetos.  Man, I hate pickles.  


After that I fell asleep for the rest of the session.  Apparently I fell asleep part of last session too, although I didn't believe Sarah at first when she told me.  So, that was several hours of sleep.   When I got home, I slept a few more hours.   It was a struggle to stay awake last evening.


When it was actually night, however, I couldn't sleep well at all, despite Ambien.  I don't think I got too much sleep, though, I was exhausted.  I didn't work today, and I did take two more naps.  In between that I watched two Spring Training games (well, parts of) on MLB network.  I'm just amazed at how hard this session hit me.  Maybe because my ANC is 200?  Maybe my nutrition hasn't been good enough?  I sort of doubt both.  We've been working on healthy meals.  I'm definitely behind in my fluid intake recommendations, but I always am (even pre-cancer).


One piece of advice I got from a colleague who's close friend had just gone through Hodgkin's said sometimes you just have to "Embrace the suck."  I guess that's what I did today.  Sarah said some days I'd be really tired and there is little point in fighting it.  So, I did lay around much of today in the hopes I have renewed energy for work tomorrow.  That's the plan anyway.

Any port in a storm

Yesterday, I got a new port.   I had recently written about my new line and getting it removed.  As a result, I now have a Bard Power Port.  It took most of the day yesterday to get it.  Or rather, it took about 30 minutes, but totaled over 6 hours at the hospital, at least an hour of which was sitting in interventional radiology as they prepped.

The circumstances surrounding this were far from ideal.  My oncologist chose the Hohn line I lost since it would likely have a lower risk for infection.   When you get a port, an incision is made, and they have to create a pocket under your skin, and then this is slipped in there, and then the line is routed to eventually spill into your jugular.   With the hohn, it wasn't tunneled, and so it went directly to the vein.  This procedure has some risks, especially when you have an ANC of 500.  In fact, I told a fellow Hodgkin's patient the following:  "As I laid on the table thinking about getting a 'procedure' under the far from ideal circumstances of a pretty decent neutropenia, I had little mental pep-talk with the few WBCs I do have left.  I reminded them to think about the outnumbered men at Valley Forge.  Hopefully they listened."  I don't normally talk to myself, or worse, my own cells, but I had little else to do while waiting during prep.


The procedure was performed under conscious sedation again.  I know I got fentanyl, but I'm unsure which benzodiazepine I got.  I don't think I got midazolam, and I didn't think I got that two weeks ago when I got my line.  The reason is that I definitely recall at least some of the procedure.  I was aware of them manipulating that port reservoir around under my skin, but the beauty of conscious sedation is that you really and truly do not care.  You simply lie there happily enjoying the altered reality.  When I got back to my room, I was still feeling very good.  It took about 2 hours until the meds wore off and I started feeling sore.  

The oncology nurse who scheduled this for me told me I would be quite sore for days.  The port is on the left side of my upper chest (the right side is still healing), and it is several inches above the nipple line.  It does poke out of the skin.  You can see and feel the line going up into the neck.  Right now it is bandaged, and must remain so until tomorrow (Sunday).  They used a type of superglue over the stitches, so, hopefully this wound is somewhat more impermeable, much like skin.  My #1 goal is to not get infected.   Anyway, the soreness is right at the site of the port, radiating a few inches in all directions, but longer up towards the neck.   Despite two percocet, getting sleep was pretty difficult.   They suggested an ice pack, and I did it twice last night.  Probably will again soon after finishing this blog post.

Monday I'll have my oncology appointment, and I'll get to use this for the first time for chemotherapy.  I do not plan on letting them draw blood from it, I'll get peripheral sticks.   

With the Port came an entire kit (seen below), including a "livestrong-style" bracelet in grey, a wallet card, and a keychain, all to alert others you have this port.   Right now, I'm trying to imagine the circumstances where this might be helpful.  In other words, should I put this on my keys and wear the bracelet?

So, that's the important business.  Here is an interesting story from Thursday:

Thank you, Lucy.  On Thursday night I was supposed to have dinner with a friend.  I got home from work at the normal time, and I found our house a total mess.  It was a mess that immediately screamed only one thing was possible, even from the first instant of seeing it:  One of the dogs was loose (we crate them during the day), and that dog was Lucy.  

There was shredded toilet paper all over the family room.  A huge piece of it leading back to the bathroom.   There were at least 3 separate piles of poo on the hardwood floor downstairs.   The pillows were thrown around.   And as I'm staring at it, I hear the all-too-familiar jingle of dog tags.  She came running down the stairs, but she knew she was guilty and immediately, out into the backyard she went.  

When I got to our bedroom, the scene was even worse.  She had gotten into our closet and specifically targetted MY things.  I found many of my expensive cycling clothes in a pile, with some shirts, a few of Sarah's sweaters, and some hats.   She had destroyed one of my hats as you can see.

 So, I guess now I have some sort of Milwaukee Brewers yarmulke, if I were to put it on my head.  Additionally, she left two additional piles upstairs, one next to our bed, and the other on it!  I honestly cannot figure out why she would make the effort to jump up onto the bed to poop there.  She also targetted two of my other favorite Brewers hats, and one, while not ruined, was full of her thick boxer drool.

She tore up the inside of the hat pictured below, and I may have to replace it, but today I went and picked up a ball cap buddy.  The clerk at Lids said it actually did work, although not to use it in the washer, as it would ruin the hat, and rather use the dishwasher.   (The info with it suggests you can use either).   So, it actually does seem to work.   Even though the inside of this hat is a little torn, it may still work.  Who knows?  Maybe it'll even be more comfortable now.

  

So, hats are obviously important to a bald guy.  That's not the point of this story.  Hopefully, it is funny to some of you.  It wasn't funny to me Thursday evening, but by Thursday night, once I realized that no actual clothes were ruined, it was.   Cleaning up the poop was no fun (especially after it dried on the hardwoods), but puppies are puppies.  Much like Lucy's last naughty episode, it was nice to enjoy a "normal person problem."  I'm still worried about a port infection, but at least I have some other things to worry about as well - or actually, not really spend much time worrying about at all because they really aren't that big of issues in the grand scheme of things.

More Thanks and other stuff

Today's update will be pretty short, but pretty important as well.  I'd recently written about how my friend Dave will be riding in the Scenic Shore 150 Bike Tour for the Leukemia and Lymphoma Society.  His goal was to raise $1000 for this outstanding organization and as of today, he has reached that goal!  You can see his pledge page here, and below is a screenshot as of this blog post.

So, a HUGE Thank You to everyone who has supported him!   He sent me an email earlier today and I know it means a lot to him, and likewise, it means a lot to me.  For those who still wish to support him, definitely feel free.

THANK YOU!!

Other miscellany of today:

1) My line site is definitely healing up.  It is gross and crusty and itchy, but as one of my colleagues very wisely pointed out, better than weeping and oozing.  That's a great perspective and I was thankful for it.  I'm beyond worrying about this current site as a place for infection.  No word on what the next line plan will be, but I'm dreading finding out anyway.

2) I read a great article this weekend in Bloomberg Businessweek.  This is a magazine I've been getting in the mail (for free) for years, but the cover story of the current issue really grabbed my attention.   You can read it HERE:  Lessons of a $618,616 Death.  It is their cover feature, so it is slightly longer than average, but an unbelievably quick read.   It is not deep into business concepts, it isn't even deep into capitation concepts.   Briefly, the author explores some of the costs and charges of her husband's lasts years against the backdrop of his terminal cancer.  The reason I think this story is absolutely phenomenal is because it explains transparently without editorializing, which would have been so easy to do in light of our current health care debate.  In fact, I love her conclusion because it is so much more complicated than the talking points bantered about currently, and yet so much simpler.    I really hate to quote any of her conclusion here, because the article is so much better taken as a whole, but I do realize some are too pressed for time for the whole thing, so I will.   Reader's Digest background:  Her husband was found to have incurable kidney cancer which eventually spread to his lungs.  Both the author and the patient dove into heroic measures to save his life including clinical trials with experimental drugs.  Eventually, he died anyway, but his life was prolonged beyond typical expectation.

Looking back, memories of my zeal to treat are tinged with sadness. Should I have given up earlier? Could earlier hospice care been kinder? I hadn't believed Terence was going to die so I had never confronted any of those dilemmas. And I never let us have the chance to say goodbye.

I think had he known the costs, Terence would have objected to spending an amount equivalent to the cost of vaccine for nearly a quarter million children in developing countries. That's how he would have thought about it.

But when I ask myself whether I would do it all again, the answer is—absolutely. I couldn't not do it again.

The average patient on Flaherty's trial got 14 months of extra life. Without any treatment at all, Flaherty estimates that for someone with Terence's stage of the disease it was three months. Terence got 17 months—still within the realm of chance but on the far-right side of the bell curve.

Only I know that those months included an afternoon looking down at the Mediterranean with Georgia from a sunny balcony in southern Spain. Moving Terry into his college dorm. Celebrating our 20th anniversary with a carriage ride through Philadelphia's cobbled streets. A final Thanksgiving game of charades with cousins Margo and Glenn.

And one last chance for Terence to pave the way for all those other poor sonsabitches.

Businessweek's back page editorial on Health Care Solutions, by Clayton Christiansen, can be found here, and it is somewhat interesting as well.

3) A lego-project of epic proportions:   Last week I ordered myself a Bowflex from Amazon, because they had a much better price than anyone else.  This model seemed to get better reviews than the models on either side of its price point, and there are tons of exercises you can do.  I thought it would be a decent complement to my time on the trainer.  I hate weight lifting and haven't done it since HS football.  Still, I've kind of been intrigued by Bowflex for years, and I expect this will be a decent way to maintain some strength through chemo, and hopefully burn enough calories to make room for the candy and sweets I so love.  But reading the assembly manual leads me to believe that it'll probably take me a week to put the eleventy-billion pieces together.  I cannot even imagine how they got it in this box.  

One Step Back...

My line lasted me 6 days.  I got it last Friday, and it was yanked today.  For those 4 or 5 hours on Monday during chemotherapy, though, it was a glorious thing.


As I noted previously, my skin was having a very difficult time with the bandaging.  Is this a tape allergy?  Is this more skin-related problems due to Hodgkin's?   I honestly have no idea, but it was clearly getting worse.  Each dressing change was becoming more and more painful, and when I called oncology yesterday, they set up an appointment for today, which I spent the day dreading, knowing it meant I'd need the tape yanked again.  (And more!)


The nurse who saw us today also saw us on Monday.  She was impressed with how much worse things got in just a few days.  Under the tape, I now have tons of little wounds or sores, some of which have been bleeding a little.  The oncologist on call didn't even have to physically see me to tell them to take the line out due to infection risk.   I couldn't conceivably keep it dressed, and to keep it open was a pretty big risk.


And just like that, in no time at all, my line is gone.   It is pretty difficult to think of today as anything but a step backwards.


One of Sarah's nurse practitioner friends had wisely suggested wrapping it with a Coban dressing.  This is a product that is only adhesive to itself, not to skin.  This would require wrapping it completely around my chest and shoulder, but at this point, I thought the suggestion was absolutely brilliant.   However, my dressing site was apparently far too scary to salvage, and the risk of keeping the line outweighed its benefits.


So, the plan is to discuss this again with my oncologist when she returns next week.  The nurse thought I might be a candidate for a Hickman, as it may not need as intensive dressing care as the Hohn after the initial two weeks.  Obviously Sarah and I are concerned with how to even get through those initial two weeks.   Perhaps we can consider the "Coban solution" immediately before problems begin.  The real bummer is we'll likely get to spend another entire day in the hospital getting the line, potentially next week.


The one downside however, is that I do now have a "Coban body wrap" on my chest to hold on the dressing from my old line site.  It needs to stay for 24 hours.   The only downside to this is that I'm already nauseated, and the stuff does not smell pleasant at all.   Apparently, nothing comes easy in the world of cancer treatment.


Thursdays after chemotherapy are very rapidly becoming my least favorite day of the whole 2 week process.  Today definitely reinforced that.  However, as I've noted before, it is like a night and day difference between "on Thursday" and "off Thursday."  The bright side is that in only a few more days,  things will look up again.

My sunglasses fight cancer & Why Lance Armstrong matters

From 1999 through 2005, I wasn't a huge Lance Armstrong fan.  I didn't even really follow "Le Tour" all that closely, other than to get occasional updates on TV and Sports Radio.  I did like that an American was winning, and that this was absolutely irritating the Europeans, but I wouldn't have called myself a huge fan of Lance, nor of the US Postal or Discovery Channel teams.


Now that I have finished school, residency, and school again and have more time for both cycling and watching it, I still don't have a clear favorite.  There are riders and teams I like and dislike, but for the most part I just watch for enjoyment.  What I really like is the scenery, the colors, the equipment, the chaos, and the heroic attacks, climbs, and chases.   I'm a casual fan at best.  I had hoped that Lance would do well in his second comeback to cycling, and last year he did just that.


Regardless of how you feel about Lance, cycling, his love life, or any allegations of doping, what matters most (to those dealing with cancer) is what he survived.  He was diagnosed with Stage 3 testicular cancer, but he also had metastases to his brain, lungs, and abdomen.  Although it is commonly cited that he was given a less than 40% chance of survival, I've read elsewhere that some doctors evaluated his chances to be as low as 3% for survival.  


Lance Armstrong finished his chemotherapy over a year before I even began Pharmacy School, and it wasn't until our 3rd year that we even touched upon oncology.   Despite Lance's high profile case being well known by then, it was pretty well taught that metastatic cancer was extremely difficult, if not impossible (despite Lance), to cure.  This is why Lance Armstrong matters.  He is the only person to have ever won seven Tours de France.  On the other hand, he beat metastatic cancer.  It is no wonder he stands as the world's most famous cancer survivor and largest source of inspiration.


I don't have an opinion on Lance's love life, his relationships with certain Astana teammates, nor any circumstantial allegations of doping.  Maybe all I want is to be inspired that someone with chances so much worse than my own survived and came back to dramatically improve on his life's passion.


Before I had cancer myself, I had enjoyed Lance's first book and I was impressed with the Lance Armstrong Foundation: Livestrong.  Both were inspiring to many.  I had heard firsthand accounts of how Livestrong helped cancer patients.  I'd spent some time on the Livestrong website and occasionally donated, especially if someone I knew was involved in a race or something.  Only after I was diagnosed with cancer did it really mean something to me.  The Livestrong Guidebooks (free!) were a great first source of information for Sarah and myself.  It was amazing how much we didn't know we'd be in for, but soon learned from the books.  I still refer to them on occasion, and would recommend them for anyone dealing with cancer.  (As I would his "Not about the bike" book.)


Which brings me to my new sunglasses.  The night before my big VATS operation, Sarah gave me the great gift of a Livestrong sweatshirt.  It was this one in fact, and she knew I'd been wanting it long before I had cancer.  We were pretty sure of what my diagnosis would be, but I found the gift sort of inspirational.  So, it has now been two years since I've ordered new prescription sunglasses and I was due.   I had my heart set on a pair of Milwaukee Brewers sunglasses, since they match what I wear most of the time, and yet these Livestrong ones seemed so much more appropriate for me.  (You can read about Lance's relationship with Oakley here.)  While I don't 100% agree with everything that Livestrong advocates for politically, I do wholeheartedly support what they are doing for cancer patients like myself.


Lance Armstrong's story is inspirational.  As I'm teetering on some of my least favorite days in my chemo cycle, as the stomach and mouth sores begin again, as my skin bleeds while dressing my new line, and as I slowly lose my taste for favorite foods and drinks, it is comforting to know that someone who had it so much worse got so much better.

Chemotherapy (4 of 12): 2 of 6 cycles done

Chemotherapy yesterday was a little different than the first 3 sessions.   I now have a central line.  This was placed on Friday (2/26).  Getting the line required a hospital admission, although it was for only about 5-6 hours, of which about 10 minutes was getting the line itself in interventional radiology.   The particular line type I have is called a Hohn catheter.  Mine is blue, unlike the one pictured in that link.  I had really, really wanted a port-a-cath, but due to my low white blood count, the risk of infection was deemed too high.


My arms are now spared, but I have this central line hanging out of my chest.  One concern I never thought of until after was the fact that it would need a dressing.  What this basically means is more adhesive, which isn't ideal in someone with a new tape allergy, or something due to Hodgkins that mimics a tape allergy. The hospital put a tegaderm dressing on it.  Due to a mix-up at the hospital, I had an "urgent" oncology visit immediately upon discharge at noon.  At this point, I was given a new dressing, made of paper tape, but still a tegaderm-like clear center.  This is pictured below.  (The urgency was nothing, btw.  All is well, other than a confused nurse practitioner).

The circular thing in the middle is a cottony biodisk impregnated with a bacteriostatic agent.   As you can see, this is a double lumen catheter.  That means one side will be used for blood draws, the other for infusions.   I'm not wild about using catheters for blood draws, as that can increase the risk of clot and infection, but oncology swears they do it all the time, and they are the boss.   This needs to be flushed with heparin (~300 units - locked), daily.   Heparin keeps it from clotting, hopefully.


So, the mission with this catheter is to keep it dry.  Hence the cling wrap and extra tape.   Due to my tape allergy, this was later changed to even more tape (paper tape), and a ton of it, also pictured below.

As you might expect, this paper tape made for a beautiful wick for water, and despite this 10 minute "lego-project" of a tape and wrap job, I still came out of the shower with the edges of the dressing wet.


And so, Sarah and I had to redress this yet again.   My skin was about as irritated as it was just leading up to the diagnosis, last fall in dermatology, of the tape allergy.  We were told that we'd expect a dressing change weekly, and by now we had changed it 3 times in 2 days.  Luckily, chemo Monday was the following day, and we had many questions for the nurses there.


By the time we got to the infusion center on Monday, and the dressing was removed, I had a bunch of tiny little blood spots from the tape.  The oncology nurses had yet another idea, and this was to dress the line simply by covering it with a 4x4 gauze, and taping that down with the paper tape.  It would still require daily dressings, but it wouldn't be quite as harsh.  (Hopefully.)  It would also still require cleaning with the disinfectant kit, and using gloves and mask, etc, but not the biodisk from above.   I'd also have to wrap it for about a week in the shower, but after that no more.


So, that is the story of my line so far.  We re-dressed it today, obviously, and the tape is still quite painful.  I'm just not sure how that is going to go over 5 months.  I have serious doubts and really, really wish I had a port.


Chemotherapy went great, however.  No more pain in my arm, and none of this dealing with hot compresses for the dacarbazine.  It is somewhat of a pain to sit for half the session with my shirt half off so they can keep checking for blood return.  I still flip between warm and cool sometimes.   I may "modify" a special undershirt for chemo next time.  We'll see.


Yesterday, chemo hit me pretty hard by the evening.  I was pretty stunned and dizzy as usual, but maybe more so.  Today was also a bit of a fog, although I was less nauseated than usual.  Hopefully that continues all week.   No taco bell this time.  Thankfully.


All in all, I was extremely thankful for this line yesterday, and I'm sure I will be more thankful as my arm pain lessens.  However, it is a little depressing to think that I have the pain of ownership of it for the next 5.5 months or so, and I only get to use it roughly 6-8 hours per month.  As long as the tape issue is kept in check, hopefully we'll be OK.  That, like so much else in my cancerous adventure, is just going to have to be day by day.