CC-4047 Cycle Eleven

Mayo Clinic Visit, January 8, 2009:

After eleven cycles of the trial drug CC-4047 and dexamethasone (DEX) my tumor burden may be starting to go up again. Last month's M-Spike was 1.0 g/dL and this month's is 1.1. The test-result printout, however, says "no significant change." And I suppose that's right. It's possible to read too much into one set of blood tests, and the accuracy of this test may not be much better than 10% anyway.

But previous tests and the results of other markers do suggest that the myeloma is coming back, if slowly. I hope not, but it seems most likely. In particular, IgG increased from 1260 to 1350, the third modest increase in the last three cycles. In contrast, though, Lambda Light Chains went down from 4.03 to 3.31 mg/dL, which might mean something, might not. They were up 24% last month, and this month they dropped back to about where they were.

Other numbers like calcium, creatinine, and albumin are fine, as is WBC the white blood cell count. AST and ALT, both a bit high last month, are back down into the reference range. Even RBC, the red blood cell count, has inched up into the reference range. So neither the myeloma nor the treatments are injuring any soft-tissue organs yet. I like that.

Here are some 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		Oct 16		Nov 13		Dec 11		Jan 08		Remarks
M-spike g/dL		0.9		1.0		1.0		1.1		Best tumor measure
IgG mg/dL		1130		1170		1260		1350		Variation is normal
L FLC mg/dL		3.14		3.25		4.03		3.31		Free light chains
Calcium mg/dL		9.6		9.8		10.1		9.9		Below 10.2 is best
Creat mg/dL		1.1		0.9		1.0		1.1		Kidney, lower is better
HGB g/dL		13.8		14.6		14.6		15.3		Hemoglobin, normal
RBC M/uL		3.97		4.19		4.20		4.36		Red cell count, normal
WBC K/uL		4.4		4.3		5.3		4.6		White cells, normal

Supplements: For quite a long time now I've been taking a rather large number of different herbal supplements, many of them specifically intended to help treat the myeloma. Over the past three months, though, I've done an experiment. For one month I just skipped the supplements, and then for the next two I took them fairly religiously. I can't be perfect - it just isn't in me - but I did as well as I could. Results: (1) The tumor burden may have gone up marginally when I took NO supplements, and (2) It may also have gone up marginally in the two months that I DID take the supplements. In other words, I have no evidence that the supplements made any difference at all. None.

I can't prove that they DIDN'T help just a little bit, either, but that's not enough. Taking a fistfull of capsules twice a day is not a treat for me. In fact it's a huge pain in the butt. I hate taking them, and they cost a lot of money. So the supplements require a serious re-thinking. I will make an appointment with our naturopath and go through them, one by one, and come up with a shorter list. Much shorter, I hope. Maybe I can get it down to a fistfull ONCE a day. There are a few supplements that are quite safe on the list, such as saw palmetto for BPH (it's a guy thing), or Vitamins D3 and K2 for strengthening bones. Those are keepers. But curcumin, EGCG, quercetin, AHCC, and resveratrol are all up for grabs. On the other hand, Margaret has been posting good information about genistein lately, and our naturopath did recommend that a few months back, so perhaps it's worth a try.

Doctor: This time I met with the nurse-practitioner Dr KDS. Here is some of the discussion:

• I'm supposed to take a stomach-acid reducer with the weekly dexamethasone (DEX) to help ward off DEX-induced ulcer. I've experienced a slight stomach discomfort on ranitidine, so for one week I tried Prilosec, the other recommended option. Later I felt a sharp pain in the gut for a half day or so, possibly at a bend in the colon. I told Dr KDS that I had taken Prilosec but not for the recommended four days in advance, and she said that four days was not necessary. No explanation for the sharp pain, but back to ranitidine.
• I asked if there was any information or simple test that could tell us whether the lesions in my bones are getting larger or smaller. X-Ray bone surveys are very inaccurate, and the PET scan is not done often because of its cost. Sigh. We myelomiacs often don't know what the myeloma is doing to us until we break a bone. Seems like there should be a better way.
• I asked if the DEX and CC-4047 were making my body age rapidly, especially my skin. She thought probably so.
• I noted that skin is continuously renewing itself, sloughing off the top and rebuilding from underneath. If that rebuilding requires angiogenesis, the creation of miniscule blood vessels, then that rebuilding may be inhibited by CC-4047 and DEX, both of which are anti-angiogenic. She agreed that might be possible, even likely.
• I asked if there were any other organs which deteriorated under the CC-4047/DEX treatment. She suggested possibly the interior of the intestines, which are also lined with tissue that constantly sloughs off and renews itself from underneath. She thought NOT the more-critical organs like the heart, liver, and kidneys, which renew themselves in a different way.
• I asked about the herpes zoster (shingles) vaccine for myelomiacs like myself who have already had chicken pox. Dr KDS said it was risky for immune-compromised people because it is a live virus, and in addition the efficacy is not very high. In other words it's not worth the risk. Insurance doesn't cover it either.
• DEX is known to inhibit "glucose transport," the transfer of sugar from the blood into the muscles which need the sugar for fuel. I told her about a recent unintentional "experiment."   I ran seven miles on DEX day, when the DEX was at maximum effect, and finished totally exhausted even though my pace for that run was slow. The very next day I ran a similar distance at a faster pace, finishing with energy to spare. Neither of us was very surprised.
• I measured my blood glucose on DEX day again, this time with the 8 mg dosage. The chart below shows glucose measurements at 40, 20, 12, and 8 mg of DEX, always taken the evening before.

I'll go down to Mayo again in another month or so. Meantime I'm still running 20-30 miles per week, hoping to increase that gradually back up to 40. Life is good.

Elevated Blood Sugar Contributes to Memory Decline

Thanks to the web site Beating Myeloma for pointing out this New York Times article about a recent study reported in the Annals of Neurology, published by the American Neurological Association. The study of 240 elderly "nondemented" subjects was done at Columbia University Medical Center.

Key findings reported in the study abstract:

• People with diabetes tended to have hippocampal dysfunction, exhibited as memory decline, and
• Elevated blood glucose (sugar) was specifically implicated as the cause of this dysfunction.

I don't have access to the full article, but the New York Times author had the article and gives quotes from one of the authors. Here are some other findings and implications reported in that New York Times article:

• Using MRI, researchers actually observed reduced blood flow in key parts of the brains of people with elevated blood glucose;
• The effect (memory loss) can be observed even when levels of blood glucose are only moderately elevated;
• Glucose regulation worsens with age; and
• Though the age-related change may be subtle, the increase in blood glucose is still a risk.

Happily, though, we can all do something about this issue:

• Physical exercise has been shown to improve glucose regulation;
• Even light physical activity can help; and
• Weight loss has also been shown to improve glucose regulation.
• It is possible that drugs which lower blood sugar may help, but those studies are not complete.

Why does this matter to people who are not diabetic?

The study had nothing specifically to do with myeloma. However, those of us who are taking dexamethasone, prednisone, or another corticosteroid may have elevated blood sugar even though we don't have diabetes. We may be diabetics on DEX day. If so, the recent study suggests that we are also at risk for memory decline. What can we do?

• Exercise intentionally and regularly, and
• Maintain an ideal weight. Personally, Weight Watchers has worked for me.
• Eat well. Enjoy a plant-based diet, with grain and meat in moderation, and little or no empty carbohydrate. Vegetables, fruit, and nuts all contribute to our health, whereas soda pop and Twinkies detract from it.

What about the corticosteroid itself?

• If you're on high-dose dexamethasone (40 mg/day four days in a row), please discuss this dosage with your doctor. A landmark study has shown that high-dose DEX results in a lower survival rate than reduced dosages;
• Get a blood glucose monitor and measure your glucose several times over one day to see how well it is regulated.
• I use the Accu-Chek Active meter, which is very inexpensive and widely available. I think I bought it in a Target store.
• My non-medical opinion: Most readings should be below 125 mg/dL, especially the first reading of the morning before eating, but readings in the hour or two after meals may go higher and readings on DEX day may be higher. Any spikes over about 180 are a matter of concern.
• Again, I'm no doctor. You should bring the results and discuss the issue of steroids and blood glucose with your prescribing oncologist. If you are not totally comfortable with the answer, discuss it also with your primary care physician, who deals with diabetics on a daily basis and may know more about blood glucose than your oncologist.

Here is a personal story: After my initial visit to Mayo Clinic I was on CC-4047 daily with 40 mg dexamethasone (DEX) once weekly. Although my oncologist, Dr L, didn't ask me to do this, a couple of months later I measured my blood glucose on "DEX day," having taken the DEX the evening before. All of the 27 readings taken that day were above 120, and one was above 190. The average was 144. When I showed this to Dr L at our next appointment, she reduced my DEX dosage from 40 mg to 20 mg once weekly.

One point of that story is that the high blood glucose may have been harming me without any warning, because I didn't "feel" anything wrong. Another point is that we need to be in charge of our own health, and watch out especially for health issues that fall outside of the normal domain of our oncologists.

Be strong, be well.



Lunch: Leftover free-range no-hormone no-antibiotic bison potroast with onions, homemade organic pumpkin with pecans (crust-free pie), organic strawberries.