Wednesday, May 4, 2016

Combining alternative and conventional treatments for melanoma....a risky business!


Mother Nature is a tricky B!!!!  She can give us rains that provide our water supply and make crops grow one minute followed by torrential floods that kill and wipe out cities the next. All that is found in nature is not benign.  In the plant world, poison ivy and hemlock come to mind.  Yet we are lucky to have Vincristine, derived from the periwinkle and categorized as an essential medication by the WHO, for the wonderful cures it can provide folks suffering from leukemia, Hodgkin's disease and other cancers.  Morphine, aspirin, digitoxin, quinine, and Paclitaxel are just a few of the drugs derived from plants that have benefited humans across the globe.  Then again, we have the beauty of tics and mosquitoes along with the germs they carry from the natural world. Speaking of the littlest beings - viruses and bacteria - while they can damage the unborn, bring illness, suffering and even death - alternatively, they also allow us the enjoyment of cheese, beer and wine and the incredible life saving properties of penicillin.  All this is merely a reflection of the pros and cons of the "natural/alternative" world.  Because there is also this: 

Risk of interactions between complementary and alternative medicine and medication for comorbidities in patients with melanoma.  Loquai, Dechent, Garzarolli et al.  Med Oncol. 2016 May.  

Complementary and alternative medicine (CAM) is used widely among cancer patients. Beside the risk of interaction with cancer therapies, interactions with treatment for comorbidities are an underestimated problem. The aim of this study was to assess prevalence of interactions between CAM and drugs for comorbidities from a large CAM usage survey on melanoma patients and to classify herb-drug interactions with regard to their potential to harm. Consecutive melanoma outpatients of seven skin cancer centers were asked to complete a standardized CAM questionnaire including questions to their CAM use and their taken medication for comorbidities and cancer. Each combination of conventional drugs and complementary substances was evaluated for their potential of interaction. 1089 questionnaires were eligible for evaluation. From these, 61.6 % of patients reported taking drugs regularly from which 34.4 % used biological-based CAM methods. Risk evaluation for interaction was possible for 180 CAM users who listed the names or substances they took for comorbidities. From those patients, we found 37.2 % at risk of interaction of their co-consumption of conventional and complementary drugs. Almost all patients using Chinese herbs were at risk (88.6 %). With a high rate of CAM usage at risk of interactions between CAM drugs and drugs taken for comorbidities, implementation of a regular assessment of CAM usage and drugs for comorbidities is mandatory in cancer care. 

Given the horrible tenacity and morbidity associated with melanoma, and the fact that some of the best treatments provide only a 40% response rate, it is sorely tempting to add a dab of this and a bit of that to our chosen medical treatment plan.  Adding things like NSAIDs (mentioned recently in the post:  Celecoxib (stuff that's in NSAIDs like aspirin and advil) works synergisticaly with anti-PD1) sounds like a no brainer, right?  And while an aspirin a day USUALLY causes no harm, there are those for whom it is NOT a good idea!  In fact, most medical researchers agree...if aspirin were put before the FDA today....it would likely be a prescription medication!!!  So...just remember:  all things over the counter and 'natural' are not always good for us.  Talk to your oncologist before adding ANYTHING to your cancer treatment plan.

Wishing you well! - c

Sunday, May 1, 2016

Don't give up. Don't ever give up.


Some of what has been going on with me, some of what I've been trying to say to others with questions about their life...their cancer...their treatment choices ~ brought this beautiful man and his incredible life to my mind again...

Stuart Scott.  1965-2015.   Stuart Scott's ESPY speech

"Our life's journey is about the people that touch us...  Don't give up.  Don't ever give up.  When you die, that does not mean that you lose to cancer.  You beat cancer by how you live, why you live, and in the manner in which you live. So live!  Live!!  Fight like hell!  And when you get too tired to fight, then lay down, and rest.  And let somebody else fight for you. This whole journey thing - is not a solo venture.  This is something that REQUIRES support.” ~Stuart Scott~

Life IS a journey.  With ALL the roads, and dead ends, and pit stops, and fabulous scenic routes included.  The good, the bad, the ugly.  Also the mundane, the funny, the sad. It is the joy of a job well done, the thought of things that one could do better.  It is shared experiences and quiet time alone.  

Recently, I've worked extra at the office.  I've repainted a window sill and back porch railing since the Sucky A$$ painter we hired to do it last year (that would be me!!!) didn't go to the trouble to sand things all the way down as they should have and allow plenty of time between the application of layers for things to dry fully.  This time, the painter (that would be me!!) put in a great deal more time and thorough sanding (due to an awesome assistant...B!) so the outcome should be better.

I have been enjoying my yard...both the beauty of the work put in last year (when I managed to propagate the midnight blue irises Trina gave me...to create my own Giverny with the Johnny White beauties I already had) and several years before (when B planted the peonies and Rosie worked to create the bed of roses and azaleas in the front of the house)....



I've been reading and doing laundry and sewing surprises and talking to friends and dealing with pollen and getting gas and hurting for those I know are feeling sad and writing and worrying about different kids I am taking care of and you know....just regular stuff.  I've also been dealing with considerable right hip pain for about 6 weeks.  Don't start yelling, "You should have told me!!!" (You peeps know who you are!! And I love you!!)  I have little patience for whiners...especially when the whiner is me.  It was pretty bad.  Waking me at night.  Causing a limp.  But....it IS getting better.  And, yes...bone mets went through my mind.  It could happen. It is part of the world I live in.  And, no...I didn't stop running, or working, or playing.  I considered my options...and decided I would give it a minute...then deal with whatever it turned out to be.  It wasn't muscular.  It wasn't sciatica.  It was probably arthritic in nature...either thanks to anti-PD1 or the fact that I will be 52 soon.  I'll take that!!!  It beats any of my alternatives.

And in that spirit...this is what B has been up to...  Clearing trees.  Building a box.  Hauling dirt....

It may not look like much just now.  But, soon wild flowers will be blooming all along the path.  Bitter Sweet will be climbing over the arbor.  Tomatoes, squash, beans, radishes (Oh Lord, he's trying them again!!!), and carrots will be harvested and enjoyed.  Or not....

That's the thing.  It will be as it will be.  That doesn't mean I don't care.  It doesn't mean that I'll stop trying.  Don't give up.   Don't ever give up!

Do what you love.  Make sure the peeps you love know that you do.  Do your very best.  Then sit down and KNOW that you lived!  love, c

Saturday, April 30, 2016

Spring Fling....Across Six Aprils!!!


Yep, 6 years ago today I had the upper lobe of my right lung removed to get rid of melanoma that had decided to make a nest in my bronchus after SRS to a brain met 3 days prior.

 Here are several April and Melanoma posts that explain: Across Five Aprils

To enjoy another April is precious to me. My peeps and Mother Nature know how to do a Spring Fling right!!!!
There is Bentie's DELICIOUS fresh baked Challah!  That's khggggghallah...don't 'cha know????
Spring's flora and fauna were beautiful at home.....

Johnny White's Irises that have moved with me to three different homes.

Knock Outs!



B's beautiful peonies!


Mischievous chive blossoms.
 My own wild flowers here at home:

Some of the few star grass blossoms the critters allowed me to have.

Appropriated Columbine!

More!

Trina's Trillium!

More!

Appropriated wild azalea.

And a bit more...

Variegated Solomon's Seal
 ...and abroad...in Cades Cove...Spring brought....

A beautiful hike with Pals/Poppies!

Trillium edged streams.

Wild Oats

Showy Orchis

Obstacles that were a bit high for a little donkey!!!

The most beautiful, sweeping patches of crested iris I have ever seen!

Gigantic Dog Wood blossoms, floating among the branches.
An incredible show of Silver Bells, in the trees and as a carpet below.

A special stream with my best boy.

And yes!  We had bears!!!  One on the trail.  4 in Cades Cove.  

Across Six Aprils.  A lucky girl indeed!!  Thanks to all of you who helped me through and brighten my days.  Wonder what summer will bring.  love, c

Thursday, April 28, 2016

Sew Chaotically! - Cute little summer dress ~ M7242


There's always a story!!!  (And boys...Mat, Ed, Josh, Paul...you guys...I know this is not your thing...but...keep reading...you'll like it....)  Here's the inspiration:

The pattern:
Initially, I was planning to make View C...the sleeveless longer version.  I know...not in keeping with the inspiration, now was it?  So, fate intervened and somehow (I think I had not paid attention to the width of my fabric when purchasing) I didn't have enough material for the maxi length.  No worries...make view A...more like the vision anyhow!  That was not as easily done either, since I found a long random flaw in the fabric!!!!  A very soft washable cotton, perfect for the vision, in color, print and drape....by Jo-Ann's from Jo-Ann's.  It turned out to be both easy to work with and....well...'FLIMPY'!  Not familiar with the word?  Here's THAT story:

Brent and I went to Greece, about a year after getting married, in 1989.  We had a wonderful time.  Years later...we went back with the kids when they were in their early teens.  We were catching a flight out of Nashville and spending the night there before take-off.  Rosie and I carefully packed for the trip and made a special 'Nashville Bag'.  One we wouldn't have to take with us that would have all we needed for Nashville and the flight over.  It was Athleisure before the term was coined!  Comfy but cute for the trip, usable for workouts and jogs once there.  It was AWESOME!!!!  Along about Manchester...it has been reported that I let out a huge gasp!  Three startled faces stared at me confused about the problem.  Suddenly, one face crumpled and erupted in a bit of a scream!  (Roo!!!)  The two male faces remained utterly confused.  We did not have the well-prepared, perfectly curated, "Nashville Travel Bag" with us!!!  Explanations were given and demands to return to Chattanooga to  fetch it were made (by two of us)!  Responses were a polite, but a little excessively firm, "No!!!!  We'll stop at Walmart!"  OMG!!!!  Never, never, ever, ever shop at Walmart in Manchester, TN!!!!  The sizes range from large to huge!!!  Rosie and I finally managed to find some exercise capri's, cami's and sweaters.  Fred was tricked out in red, gigantic, nylon of the worst sort, basketball shorts (that he could have sagged with ease) and some sort of t-shirt.  But, B!!!  He went all out:  Faded Mom-Jean-SHORTS, with a Western-wear plaid shirt, replete with pearlized snaps, and flimpy socks!  There it is again ~ 'flimpy'. Yep, flimpy socks are made of very thin nylon (black in this case) that could easily be made to reach ones thigh, but that he preferred to roll down, much as your great aunt or grandma did her hose, somewhere along mid calf.  Flimpy as they were, they were constantly being "eaten" by his shoes, necessitating many adjustments in airports across the globe and were accordingly dubbed: FLIMPY!

So, yes this fabric was indeed flimpy.  Quite maneuverable when putting in sleeves, but less than stable when working on a collar or hem.  Indeed....once you have dealt with 'flimpy' you will know it forever.



There you have it.  A flimpy little summer dress.  I think it lived up to the vision rather well.  Wore it to work this week with a woven leather belt at the waist.  Lots of compliments.  But only you, dear readers, got to know about.....FLIMPY!!!!

Sew and travel chaotically!!!!! - c

Wednesday, April 27, 2016

Celecoxib (Stuff that's in NSAID's like ibuprofen and aspirin!!!) and anti-PD1 work synergistically


I put this post up a while ago: An aspirin a day keeps melanoma at bay and makes immunotherapy work better???   As I noted in that post....I figure all us immunotherapy peeps have pretty much been living on advil in order to deal with our arthralgias!!!  But, this was republished recently:


Hydrogel dual delivered celecoxib and anti-PD-1 synergistically improve antitumor immunity.  Li, Fang, Zhang, et al.  Oncoimmunology. 2015 Aug 12;5(2):e1074374. eCollection 2016. 

Two major challenges facing cancer immunotherapy are the relatively low therapeutic efficacy and the potential side effects. New drug delivery system and efficient drug combination are required to overcome these challenges. We utilize an alginate hydrogel system to locally deliver 2 FDA-approved drugs, celecoxib and programmed death 1 (PD-1) monoclonal antibody (mAb), to treat tumor-bearing mice. In two cancer models, B16-F10 melanoma and 4T1 metastatic breast cancer, the alginate hydrogel delivery system significantly improves the antitumor activities of celecoxib (CXB), PD-1 mAb, or both combined. These effects are associated with the sustained high concentrations of the drugs in peripheral circulation and within tumor regions. Strikingly, the simultaneous dual local delivery of celecoxib and PD-1 from this hydrogel system synergistically enhanced the presence of CD4+inteferon (IFN)-γ+ and CD8+IFN-γ+ T cells within the tumor as well as in the immune system. These effects are accompanied with reduced CD4+FoxP3+ regulatory T cells (Tregs) and myeloid derived suppressor cells (MDSCs) in the tumor, reflecting a weakened immuosuppressive response. Furthermore, this combinatorial therapy increases the expression of two anti-angiogenic chemokines C-X-C motif ligand (CXCL) 9 and CXCL10, and suppresses the intratumoral production of interleukin (IL)-1, IL-6, and cycloxygenase-2 (COX2), suggesting a dampened pro-tumor angiogenic and inflammatory microenvironment. This alginate-hydrogel-mediated, combinatorial therapy of celecoxib and PD-1 mAb provides a potential valuable regimen for treating human cancer.

Hmmmm.... "reduced myeloid derived suppressor cells (MDSCs)"....  Now that could be something!!  Remember this?   Increased Myeloid Suppressor cells = not so good.

And for what it's worth....there was also this back in the day:  
Nonsteroidal anti-inflammatory drugs and the risk of skin cancer:  A population-based case-control study. Johannesdottir, Chang, Mehnert, et al.  Cancer, 2012, May 29.

Knowing that Nonsteroidal anti-inflammatory drugs (NSAIDS....like aspirin, ibuprofen, etc.) may prevent the development of cancer by inhibiting cyclooxygenase (COX) enzymes, these folks from Denmark looked at NSAID use and the risk of squamous cell carcinoma, basal cell carcinoma, and melanoma.  They looked at all cases of those diseases from 1991 through 2009 in northern Denmark. (Squamous = 1,974, basal = 13, 316, and melanoma = 3,242).  They matched 10 population controls (n=178,655) to each case by age, gender, and county of residence.  Use of NSAIDs was noted via a prescription data base.  FINDINGS:  After a great deal of incidence rate ratios and confidence interval statistical shenanigans....they determined that "NSAID ever use compared with nonuse was associated with a decreased risk of squamous cell and melanoma, especially for long-term use and high-intensity use.  NSAID use was not associated with a reduced risk of basal cell.  All estimates of reduced risk were driven primarily by the use of nonselective NSAIDs and older COX-2 inhibitors."

Just putting it out there.  Best - c

Sunday, April 24, 2016

Pembro's (Keytruda's) overall tumor response and OS in melanoma patients....



Association of Pembrolizumab With Tumor Response and Survival Among Patients With Advanced Melanoma.  JAMA. 2016 Apr 19.  Ribas, Hamid, Daud, Hodi, Wolchok, Kefford, Joshua, Patnaik, Hwu, Weber, et al.

The programmed death 1 (PD-1) pathway limits immune responses to melanoma and can be blocked with the humanized anti-PD-1 monoclonal antibody pembrolizumab.

Open-label, multicohort, phase 1b clinical trials (enrollment, December 2011-September 2013). Median duration of follow-up was 21 months. The study was performed in academic medical centers in Australia, Canada, France, and the United States. Eligible patients were aged 18 years and older and had advanced or metastatic melanoma. Data were pooled from 655 enrolled patients (135 from a nonrandomized cohort [n = 87 ipilimumab naive; n = 48 ipilimumab treated] and 520 from randomized cohorts [n = 226 ipilimumab naive; n = 294 ipilimumab treated]). Pembrolizumab 10 mg/kg every 2 weeks, 10 mg/kg every 3 weeks, or 2 mg/kg every 3 weeks continued until disease progression, intolerable toxicity, or investigator decision.

Among the 655 patients (median [range] age, 61 [18-94] years; 405 [62%] men), 581 had measurable disease at baseline. An objective response was reported in 194 of 581 patients (33%) and in 60 of 133 treatment-naive patients (45%). Overall, 74% (152/205) of responses were ongoing at the time of data cutoff; 44% (90/205) of patients had response duration for at least 1 year and 79% (162/205) had response duration for at least 6 months. Twelve-month progression-free survival rates were 35% in the total population and 52% among treatment-naive patients. Median overall survival in the total population was 23 months, with a 12-month survival rate of 66%, and a 24-month survival rate of 49%. In treatment-naive patients, median overall survival was 31 months, with a 12-month survival rate of 73%,  and a 24-month survival rate of 60%. Ninety-two of 655 patients (14%) experienced at least 1 treatment-related grade 3 or 4 adverse event (AE) and 27 of 655 (4%) patients discontinued treatment because of a treatment-related AE. Treatment-related serious AEs were reported in 59 patients (9%). There were no drug-related deaths.

Among patients with advanced melanoma, pembrolizumab administration was associated with an overall objective response rate of 33%, 12-month progression-free survival rate of 35%, and median overall survival of 23 months; grade 3 or 4 treatment-related AEs occurred in 14%.

Once again it is clear that treatment naive patients do better on anti-PD1 than those who are pretreated...particularly with ipi.  Here is a post and link to the report from the Checkmate 064 trial in which folks who got nivo first followed by ipi had slightly more side effects (roughly 50 vs 43%) but they also had objective response rates of 41.2% vs only 20% in the ipi first group!!!!!!!!!!!!!!!! - Sequential nivo then ipi vs Sequential ipi then nivo

Here is a recent report on OS with nivo - Nivolumab shows impressive OS in melanoma
The data here is further out.  All patients were "heavily pre-treated", so none were treatment naive, but none had been treated with ipi.

We never can compare apples to apples, can we?  But...still....good news overall!  Way to go, Ratties! - c