Neuropathy is the Issue

Mayo Clinic Visit Thursday, May 28, 2009, end of Cycle 16:

Peripheral Neuropathy:

I posted about the possible beginnings of peripheral neuropathy (PN) eleven days ago. In those days I have taken most of the supplements listed on my Supplement Regimen page. The symptoms have not disappeared, however, though they have changed a little, and I am still not certain (beyond a reasonable doubt) that the feelings in my thumbs and feet are in fact PN from the CC-4047 medication.

There is normal sensation, or I should say no sensation, from the affected areas unless they touch something. One thumb always feels fine now, and the other, which was injured and its nerves cut many years ago, does tingle when touched, though the thumb pad is still sensitive to touch in the normal way as well. The soles of both feet also feel tingly when I walk on them, the same sort of tingle that one may feel when a limb is waking up after being "asleep" for lack of blood. Like the thumb, though, the skin of the soles of the feet is still normally sensitive to touch, and in fact the soles of the feet are still ticklish. None of this affects my running yet, nor is it really even very annoying. Yet.

Bottom line: if this is PN, it isn't very bad yet. I discussed all of this with Dr KDS at Mayo today. She advised me to keep them posted if the PN advances at all, because there are things that they can do. She talked about a few prescription medications, such as Neurontin, for managing the symptoms of PN. She did not, however, hold out any hope of a drug that would reverse the PN itself. She also mentioned that one patient had obtained good results from a machine of some sort, and will get me more information on that. When she does, if it's real, I'll post whatever I can about it.

Test Results:

I'm still on the trial of CC-4047 with dexamethasone (DEX), now taking CC-4047 2 mg every day and DEX 8 mg every Sunday night. In the past 28-day cycle IgG has gone from 1060 to 1030 mg/dL, Lambda free light chains from 2.55 to 2.60 mg/dL, and M-Spike from 0.8 to 0.9. Basically, this is no observable change, because each change is well within the measurement error of its test. Everything else is good too - calcium is up but well within range, ALT and AST are down, LDH is actually below its reference range at 130 U/L, WBC and ANC were down a bit last month but are now back up, it's all cool.

Related links:

	My Myeloma		A discussion of my myeloma, not very technical.
	My Treatment History		Not technical.
	My Test Charts		Graphic displays of several key test results over time.
	My Test Result Table		Best with a wide browser window. Very "technical."

Side effects of the two key drugs, CC-4047 and dexamethasone, are discussed in a previous post. Add peripheral neuropathy to the list.

Here are a few specific test results:

Test		Mar 04		Apr 02		Apr 30		May 28		Remarks
M-spike g/dL		0.9		0.9		0.8		0.9		Best tumor measure
IgG mg/dL		923		1060		1060		1030		Variation is normal
L FLC mg/dL		2.64		3.04		2.55		2.60		Free light chains
Calcium mg/dL		9.7		9.5		9.6		10.0		Below 10.2 is best
Creat mg/dL		1.0		1.0		0.9		1.0		Kidney, lower is better
HGB g/dL		13.7		14.7		14.3		14.4		Hemoglobin, normal
RBC M/uL		3.89		4.26		4.01		4.06		Red cell count, low
WBC K/uL		4.5		4.2		3.6		4.0		White cells, normal

Doctor:

Sunshine and I also discussed with Dr KDS:

• Mayo has seen some patients on CC-4047 develop peripheral neuropathy, as they might with thalidomide or Revlimid. There is not yet enough information to say how likely or how serious this side effect might be.
• Dr KDS is going to ask a dermatologist if there is anything to be done about thinning skin from the DEX.
• She confirmed that the DEX can cause wounds to heal more slowly. It seems to take a month now, instead of a week or two, for a little cut to heal.

Grapefruit:

Since about Christmas I've been eating a grapefruit every day. Grapefruit can increase the potency of some drugs by inhibiting a digestive process that would normally reduce the amount of drug that can go from the stomach into the blood. We have wondered if the grapefruit has played a part in the good M-Spike results in recent months by increasing the concentration of CC-4047 in my blood. Now, of course, we also wonder if it might not increase the severity of peripheral neuropathy symptoms if I'm getting more CC-4047 than expected. Therefore, for the next month, no grapefruit for me. Too bad - I've been looking forward to that daily refreshment.


Organic oatmeal, organic strawberries, organic grapes, mango, banana, organic walnuts, organic nonfat milk.

Stewart Asquith Died

Stewart Asquith was a professor at the University of Glasgow, Scotland, teaching and researching in the field of children's rights. And he was one of us, a myeloma survivor, until April 13, 2009, when he died in Edinburgh, from myeloma and its treatments. He blogged about those on Stewart, Myeloma, and Revlimid. An inspiring account of his life is posted on The Scotsman magazine. Quite a man.

In the last several years Stewart lived life to the max, taking vacations with his wife Elspeth, restoring classic bicycles and building his own recumbent, building a solar energy collector for his roof, renovating a bathroom, sailing on an ancient fishing vessel (pictured), on and on. All this time he went through a transplant, radiation treatments, surgeries, high-dose steroids, insulin, and more. He was an irrepressible soul who could be stopped in only one way.

I knew Stewart only from his blog and a short exchange of emails, but I have some Scot blood in me and feel an odd affinity toward this human dynamo. The world is a bit poorer at the loss of Stewart Asquith. We shall miss him and I do miss him.

Colloid Nodule of the Thyroid

The thyroid nodule (previous post) is a "colloid nodule," apparently quite benign. Doctor L says take another look with ultrasound in six months or a year, see if it's growing. Otherwise it's fine if it isn't causing problems breathing or swallowing.

It's not. This drama is over.

I did actually increase my iodine intake a couple of months ago, so maybe the treatment, if any is needed, is already underway.

Hearing Exam Leads to Thyroid Biopsy

My hearing isn't great. Down about 20 db in one ear, which is the bottom of "acceptable," and down much more in the other. So I visited an audiologist who recommended hearing aids, but who first scheduled me with an ear-nose-and-throat (ENT) specialist because she thought the big difference between the two ears could indicate a medical problem. I've had this difference for decades, but I went anyway.

Dr D, the specialist, did an examination of the ears and of course found nothing. Then, because he is an ENT, he looked in my nose and checked my throat. "Did you know about this nodule on your thyroid?," he asked. "News to me!," said I. He explained that he always does the cursory examination (he may not have used the word "cursory") without expecting to find anything, but this time he did. He said it was about a centimeter and a half in size, and recommended an ultrasound exam to check it further.

So today I expected an ultrasound examination of a nodule on the thyroid. But it turned out to be ultrasound imaging immediately followed by a fine-needle biopsy - both had been scheduled because the nodule was large. I believe that the biopsy is indicated for nodules exceeding 1 cm in size, and K, the technician, said this one was 2.6 cm in the largest dimension. As she pointed out, that's just over an inch. I'm a little surprised that I didn't know about it.

They removed my shirt so that it would not get Betadine on it, then swabbed the area abundantly with the Betadine, and finally applied a hypo of lidocaine. Almost immediately, Dr M, the radiologist, started taking samples of the nodule with very small gauge (#25) needles. I felt the first two needles, because the lidocaine hadn't quite taken effect, but the pain was really quite minor so I didn't complain. Anyway, complaining would mean talking, which is not a good thing with a needle in the neck. The nodule was close to the carotid artery, which they refer to as "Big Red" and avoid at all costs.

Dr M explained that the nodule was not homogeneous, and he was taking samples from different areas. I couldn't see the ultrasound screen, so I watched him. Once he had the needle in my neck his eyes never left the screen until he withdrew the needle again. Totally guided by the imaging. He took four samples, then stopped, explaining that they would send these to the pathologist who would tell him in a few minutes whether he had enough cells.

Meanwhile K asked about my myeloma and shared that she herself was a 2 1/2 year survivor of an allogenic umbilical-cord stem-cell transplant for leukemia, done at the University of Minnesota. Her doctors had said that her acute leukemia was not treatable with chemotherapy, but she had a 50/50 chance of survival with a stem cell transplant. She chose allogenic, despite the lifelong issue of graft-versus-host disease, because she believed that the result, if she survived the transplant, would more likely be a cure. So far so good! No trace of the leukemia. After two years they call it "remission," and she's there. She looks great. Perhaps 25 - 30 years old, I hope she has a long life ahead of her.

Back on the biopsy table, Dr M informed me that the pathologist was not satisfied with the sample. Thus more lidocaine, and this time a larger-bore biopsy needle, a #22. Apparently, needle sizes are like wire sizes, smaller numbers indicate larger needles. But I didn't feel any of these needles, and I think he used six more. He actually ran out and had to use one of the smaller ones.

We waited another 20 minutes and were told that they probably had enough. Dr M did mention that the pathologist had not seen cancer cells in his cursory examination of the samples, and that's a good sign. It can change, of course. In addition, there is always the chance that the pathologist will change his mind about the size of the sample, but if that happens we'll schedule another biopsy and this time they'll use a needle that can cut off a chunk. They don't like to do that on the neck, said Dr M, but he didn't explain why. Of course there's always the risk of hitting Big Red, and I suppose there's also a risk of hitting nerves or something. There's a lot of stuff crammed into the neck. Come to think of it, they made me sign something after the initial ultrasound and just before the biopsy. Perhaps it was the "informed consent" sheet, which of course I didn't read. Who reads a clipboard when they're already flat on the table?

It takes the pathologist 48 hours to crank out the final report, according to K. So I guess I won't know until Friday at best. In the meantime I'm not too worried. My thyroid function tests have been normal, and what the hell, I already have cancer.



Breakfast: Organic oatmeal with dried cranberries, blueberries, organic apple, organic pear, organic strawberries, orgnic walnuts, and organic nonfat milk. Not shown: Two organic eggs cooked in good organic oils.

Peripheral Neuropathy Treatment

It's here, perhaps. Maybe. I hope not. In the past few days I have felt a tingling sensation in the very tips of both thumbs, becoming much stronger when I touch the skin there. Nothing in the fingers yet. But in bed last night I noticed a numbness in the sole of my left foot; not so much the toes as the ball of the foot and nothing in the right foot yet.

That's all so far. Not enough to affirmatively declare that peripheral neuropathy (PN) is upon me, but enough to be a little scared. PN can be very painful and, when body parts go numb, rather disabling as well. It usually begins in the sensory nervous system, but can even progress to the motor nerves, resulting in partial paralysis. It is to be avoided if possible, and in my opinion it should be accepted as a necessary consequence of treatment only if all other avenues of treatment have been exhausted.

In Myeloma patients PN can be caused by at least three different things:

• Myeloma-specific chemo drugs such as thalidomide. I'm not taking thalidomide any more, but am taking CC-4047, a thalidomide derivative.
• Dexamethasone (DEX), which I am taking, and which (I believe) can cause symptoms of diabetes, one of which is PN.
• The myeloma itself, especially if protein or light-chain counts are high. Mine are not, as of two weeks ago.

I have another Mayo appointment in two weeks, when this subject will get some genuine medical attention. Furthermore, by that time, I will have a better idea whether or not I really do have PN.

In the meantime I'm trying to learn about it, and do whatever I can to mitigate the problem. Happily for me, the leaders of the Minneapolis Myeloma Support Group handed out a sheet of information on PN treatment at yesterday's monthly meeting.

Dana-Farber Cancer Institute:

That sheet, it turns out, was a printout of a web page which was transcribed from a paper handout at Dana-Farber. A myeloma survivor (Beth I think) has posted that handout HERE on the website MMSupport.net, which also has lots of other good information about myeloma and treatment. To summarize the sheet:

• Multi-B vitamins with B1, B6, B12, folic acid, and the other B-vitamins. Dosages: B6 100-200 mg, folic acid 1-2 mg.
• Vitamin E 400 IU daily.
• Fish oils with the omega-3 acids EPA and DHA.
• Evening primrose oil capsules.
• Flax seed oil.
• Amino acids. No further description.
• Alpha-lipoic acid (ALA) 200 mg twice daily, within 2 hours of a meal.
• Acetyl L-carnitime 500 mg twice daily, within 2 hours of a meal.

The same page gives advice for cramping, and also has a list of prescription drugs. I get the impression from members of our support group that the best of those drugs come with their own list of significant side effects. On the Dana-Farber.org website itself there is another Q & A page listing non-prescription alternative & nutritional self-treatment for PN. Summary:

• Vitamin B6, 50-100 mg/day.
• L-glutamine, 15 grams twice daily. Find a brand with no fillers.
• Alpha-lipoic acid 300 mg twice daily for up to four weeks, then consult a dietitian or doctor.
• Acupuncture.

MD Anderson Cancer Center:

MD Anderson is currently running a trial of oral alpha-lipoic acid versus a placebo for chemotherapy patients. Further, there is a PDF document on the MDAnderson.org website in which Dr Oh discusses diabetic PN. He suggests vitamin E, vitamin B, and L-acetyl-carnitine (same as acetyl-L-carnitine).

Mayo Clinic:

I didn't find much on the Mayo Clinic web site except for one reference to the use of vitamin B-12 to prevent PN. However, I know that Mayo did a study with intravenous ALA which showed marked improvement for patients with diabetic neuropathy. I just can't find that study right now.

Naturopathic Community:

This is a large community and I haven't done much of a search yet, even though naturopathy may be the best bet for controlling symptoms of PN. The first website I came across suggests B-12, ALA, and L-glutamine, with additional supplements if poor circulation is suspected.

International Myeloma Foundation (IMF):

I found one good video presentation from last December's Myeloma Workshop in Washington DC. Dr Paul Richardson, from Dana-Farber Cancer Institute described research on the cellular mechanisms that appear to cause neuropathy, and gave a quick list of possible complimentary treatments:

• Multi-B vitamin, folic acid, and vitamin E.
• Alpha-lipoic acid, L-carnitine, and L-glutamine.
• Magnesium and potassium.
• A daily multivitamin.
• Topical emollient creams containing cocoa butter with spearmint or menthol. He explained that the injured nerves are in a very thin layer just under the skin and these creams might be able to stimulate them.

Margaret's Corner:

In a recent post, Margaret's Corner, an important source of information regarding myeloma treatments, states that curcumin can help alleviate and possibly reverse peripheral neuropathy from chemotherapy.

Georgia Cancer Treatment Center:

Sunshine found this newsletter which suggests:

• Bromelain 200-400 mg three times daily
• L-glutamine 10 grams three times daily, and
• Vitamin B-complex. It also points out that bromelain is abundant in pineapple, and that it also treats other maladies such as bruising, arthritis, bunions, bursitis, tendonitis, carpal tunnel syndrome, gout, and sinusitis.

A Regimen:

It turns out that I am already taking many of the supplements that are recommended above, though some in lower quantity than recommended. I will modify my supplement regimen so that it includes:

• A daily multivitamin.
• A good multi-B (e.g. B-100), with added B6 if necessary to get 50 to 100 mg/day but not more than 100 mg.
• Vitamin B-12 sublingual 1000 mcg daily.
• Alpha-lipoic acid 300 mg twice daily.
• Acetyl-L-carnitine 500 mg twice daily.
• Vitamin E 400 to 800 IU daily, but not more than 800.
• L-glutamine 15 to 30 grams per day. Wow.
• Curcumin 500 mg daily.
• Flax seed oil 1000 mg per day. Maybe fish oil too, but I need a reliable source.
• Bromelain, amount undetermined just now.

If that doesn't solve the problem, then I'll consider:

• A visit to my naturopath for her advice. Might do that soon anyway.
• Altering the chemo to reduce symptoms, such as three weeks on and one week off instead of the current four-weeks-on regimen. Mayo Clinic will have something to say about this of course - I'm in a trial.
• Acupuncture.
• Evening primrose oil.
• Magnesium and potassium, more than I now get in food and the multivitamin.
• Topical creams with cocoa butter and spearmint or menthol.

Your Turn:

This is a huge subject, barely touched in this blog post. If you have suggestions or information, please do comment. Sometimes the comments are much more helpful than the post itself. Thanks,

Don

Even Better News, Probably

Mayo Clinic Visit Wednesday, April 30, 2009, end of Cycle 15:

Results:

CC-4047 is an analog of thalidomide and Revlimid, presumably an advancement on both. One little-advertised feature of Revlimid is that a patient's M-spike may decline in two phases. The first phase may take the spike down to a plateau, and if there is a second phase it may produce another gradual decline to even lower numbers, possibly much lower. Dr L has a theory that the first phase may be the Revlimid actually killing the naughty plasma cells, as we might expect, and the second may happen because the Revlimid has helped the immune system itself to fight the myeloma.

The good news for me, perhaps, is that CC-4047 seems to show the same two-phase response for some patients, maybe including me. The CC-4047 study is less than a year and a half old, so information is still somewhat tentative. My own M-spike initially dropped rather quickly from 2.7 to 1.1 g/dL, then to 0.9 and back up to 1.1. In the past four cycles, though, it has gradually dropped again, from 1.1 down to 0.8 g/dL, the lowest level we have seen in the fifteen 28-day cycles that I have been on the study. I can only hope that this is the beginning of the second gradual downward movement.

IgG stayed the same, at 1060 mg/dL, suggesting that the drop in M-spike might be illusory. M-spike is known to be a relatively inaccurate measurement, and indeed the the printout says "no significant change since the last measurement," even though it dropped from 0.9 to 0.8 g/dL. However, since January the drop is from 1.1 to 0.8, enough to be significant. The trend is certainly down, not up.

The only iffy test results are the white blood cell and neutrophil counts, both of which took a bit of a dip this month. CC-4047 can cause those counts to tank, which is not good. But they bounce around a bit and have been low before, so we'll see next month. We live month to month, and I'll take this one!

Related links:

	My Myeloma		A discussion of my myeloma, not very technical.
	My Treatment History		Not technical.
	My Test Charts		Graphic displays of several key test results over time.
	My Test Result Table		Best with a wide browser window. Very "technical."

Side effects of the two key drugs, CC-4047 and dexamethasone, are discussed in a previous post.

Here are a few specific test results:

Test		Feb 05		Mar 04		Apr 02		Apr 30		Remarks
M-spike g/dL		1.0		0.9		0.9		0.8		Best tumor measure
IgG mg/dL		1160		923		1060		1060		Variation is normal
L FLC mg/dL		2.78		2.64		3.04		2.55		Free light chains
Calcium mg/dL		9.7		9.7		9.5		9.6		Below 10.2 is best
Creat mg/dL		1.0		1.0		1.0		0.9		Kidney, lower is better
HGB g/dL		14.9		13.7		14.7		14.3		Hemoglobin, normal
RBC M/uL		4.28		3.89		4.26		4.01		Red cell count, low
WBC K/uL		5.0		4.5		4.2		3.6		White cells, normal

Doctor:

Sunshine and I discussed a few other things with Dr L:

• It seems as if the dexamethasone (DEX) had aged me five or ten years in the last year, noting especially the thinning skin and wasting muscle. Dr L was not surprised.
• It also seems like there are two DEX days now, not just one. The DEX effect seems to last longer. Again she was not surprised.
• She had mentioned in an earlier visit that the body does become more sensitive to the DEX as time passes. This time she said that this unfortunately applies only to the side effects and not to the efficacy of the drug.
• When I asked about the effect of the drugs on the thyroid, she mentioned that the IMiD drugs (thalidomide, Revlimid, and probably CC-4047) can sometimes inflame the thyroid, and in the worst case can cause the thyroid to "burn out," eventually resulting in hypothyroidism. This is why the CC-4047 study protocol calls for a TSH test every three cycles, which is frequent enough to catch the problem. My TSH was 2.0 mIU/L, which is fine.
• We discussed a reduction in the DEX dosage, from 8 mg to 4 mg once weekly, but because of the good M-spike result we decided to change nothing. I love life more than I hate DEX.
• I have eaten one grapefruit every day since about January, which is roughly when this M-spike decline began. Coincidence? She was not certain whether grapefruit would have an effect on the strength or efficacy of either the DEX or the CC-4047. But I'm not inclined to change that either.
• Don's basic rule of life: "If it works, YOU CAN'T FIX IT." Corrolary: "So don't try."
• We had quite a discussion about the shingles vaccine. It is a "live" vaccine, so there is a theoretical possibility that it could actually cause a case of chicken pox in an adult with a compromised immune system. That could be horrible and maybe even fatal, so oncologists simply don't give that vaccine to people with myeloma and there is almost no clinical information on whether myeloma patients would actually develop chicken pox from the vaccine.
• My primary care physician, Dr PCP, had suggested the vaccine and he's a very smart man, so I'm still thinking about it. As far as I know, my immune system is as competent as it has ever been. If it's safe for normal adults, it should be safe for me. Shingles is pretty nasty too.
• In February the electrocardiogram (ECG) report said "Ventricular escape beat followed by SVPC." I'm not even sure what that means - I hope it was just because I have a runner's heart and I was on a lot of caffeine that day. Anyway it wasn't there this time.
• But this time the report says "minimal voltage criteria for LVH, may be normal variant." This same statement appeared once before too, about a year ago. I think it's the measure of the height of the major voltage spike on the ECG. Dr L said that the voltage can show higher on lean people (like runners), and I also think it has to be higher for a person with a very low heart rate, because the heart has to pump harder on each beat. A normal heart rate is 60 or so, but mine was 40 for that ECG - normal for me because I'm a runner. I'll ask Dr PCP about this.
• We talked briefly about new drugs. She mentioned a drug called Zevalin, a monoclonal antibody with the capacity to kill the progenitor cells ("stem cells"), perhaps to be used in combination with melphalan which kills the mature myeloma cells. Apparently someone at Mayo is doing work on this. If this were successful, we might actually be headed for a cure. Yikes.
• The CC-4047 study has been reopened more than once now for a modest number of additional patients. The last opening, now filled, was for people for whom Revlimid has failed. This time it is for people for whom both Revlimid and Velcade have failed. Apparently the FDA does not want to approve another new drug unless it shows a significant advantage over drugs already available. If CC-4047 works for those hard-to-treat patients, it will certainly show that.
• I asked if the muscle wasting caused by DEX would affect my heart as much as it affects leg muscle. She thought not, because the heart is "smooth" muscle, different from motor muscles.

Three days before the Mayo visit I saw Dr PCP with a lits of questions about DEX and a few other things:

• I asked if there was a way to minimize the muscle-wasting effect of DEX by timing my running and other exercise properly. Is it best to exercise on DEX day, or is it best on the day before or the day after? He didn't know, but will look into it. Good guy.
• He mentioned that immunizations, such as the flu shot, are rendered less effective by DEX, which suppresses the immune system and thereby its response to the vaccine. He thought perhaps the best timing for that would be two days after taking the DEX.
• The reason that DEX is used for us instead of prednisone is that there is less problem withdrawing from DEX, so it's better in applications where the corticosteroid should be pulsed instead of continuous.
• He knows of no way to toughen thin skin. Tsk.

The end. For now.



Dinner: Wild-caught Alaskan sockeye salmon (canned) with organic yogurt and a little cheese, toasted slivered almonds, organic green peas, organic strawberries. Life is good.