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.

Good News Again

October 16, 2008:

Eight four-week cycles of the phase-II trial of the new Celgene drug CC-4047 are now complete, and overall results are great. M-spike dropped again this month from 1.0 to 0.9, just a third of the high of 2.7 at the start of the trial. YAY! IgG is virtually unchanged, and Lambda free-light chains (FLC) are up a little but so are Kappa chains, and the ratio is actually a bit higher (better).

White cell and red cell counts are mostly unchanged, also good. Blood pressure, which was about 150/80 two months ago, was down to about 122/58 this month, probably because Dr. L has reduced my dosage of dexamethasone (dex) from 20 mg once weekly to 12 mg. That 12-mg dosage will continue for the ongoing ninth cycle. The entire protocol as prescribed by Dr. L is detailed in a previous post.

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.

Dexamethasone affects (increases) the level of glucose in blood, which is not good. Therefore, although I am not a diabetic, I occasionally use a blood glucose meter. In March, when I was taking 40 mg of dex, I measured blood glucose at roughly half-hour intervals on "dex day," and again several days later when the dex had worn off. In May, when taking 20 mg of dex, I measured it again on dex day. Last Monday was dex day once more, like all Mondays, and I made those measurements after taking 12 mg of dex the night before. Here is a chart that shows the results for 40 mg, 20 mg, 12 mg, and no dex. It's a busy chart, but the bottom line is: 12 mg of dex last Monday resulted in blood glucose levels at least as high as they were with 20 mg of dex last May 19, almost five months ago. That was a surprise to me but not to Dr L, see the first item below.

Some subjects that came up:

• It appears that a person's sensitivity to dexamethasone increases with use. Therefore, after a time, a lower dosage of dex will produce much the same effect as a higher dosage did previously. We were discussing side effects when Dr L mentioned this, so I do not know if that also applies to the anti-myeloma benefit of dex.
• I asked whether or not it was time to harvest stem cells against the eventuality of a stem cell transplant. Dr L responded that the CC-4047 phase-II trial protocol does not provide for the interruption required for a harvest, so I guess I will wait until the trial is over. I'm OK with that - the trial will not end for me as long as it continues to reduce my counts or hold them steady, and there is NO chance that I will want a transplant until CC-4047 fails to do that.
• Long-term dex usage can cause avascular necrosis of the bone, which is bone death attributable to insufficient blood supply. Most commonly this occurs in the hip, at the head of the femur, but it can happen in other places. I asked if I was a candidate and Dr L said it was possible, though I got the idea that I'm not really into "long-term" yet after only eight months. Further, she did not indicate that the risk was very high. I would like to think that my highly-active lifestyle might help too, but we did not discuss that.
• I asked about the half-life of myeloma cells, and she thought that it would be a property of a person's particular myeloma and would vary a great deal from one individual to another, though probably measured in months in most cases.
• The half-life of normal plasma cells is also quite variable. They are responsive to threats perceived by the body, and a few of them even become "memory B cells," which live for a very long time and retain patterns for the immunoglobulins required to neutralize the threats they have seen.
• We did not discuss this, but I believe that researchers at Johns Hopkins have identified some of these "memory B cells" as the wacko and hard-to-kill progenitors of new myeloma cells.
• Dr L recommended the flu shot and suggested November as the best time to get it. Since the shot has a limited period of effectiveness, November constitutes a balancing of the risk in the fall versus the risk in the spring.
• The Myeloma group at Mayo is moving from the Gonda Building to the Mayo Building on November 1.
• She asked about muscle weakness, particularly in the shoulders, upper arms, and quads. I am not having any problems, except that it takes an hour longer now to finish a marathon. I'll get back to my resistance exercises and try to quantify any other muscle losses.
• CC-4047 seems to be less "myelosuppressive" than Revlimid, which means that it does not harm the cells of the bone marrow so much and therefore does not suppress red and white cell counts as much. In my case there is only a barely-noticeable difference attributable to the CC-4047/dexamethasone trial.
• We discussed nifuroxazide, the subject of a recent article in Blood Journal. It's a 40-year-old antibiotic, used especially in Europe, for treatment of certain types of diarrhea. Researchers in Boston have recently discovered that it can selectively kill myeloma cells in the lab, though no studies have been done with real live humans yet. I learned of this from Beating-Myeloma, and I think it was new to Dr L. She cautioned that it's still a long way from actual use by patients, of course. Nevertheless, I suppose that if I were at the end of the treatment road and nothing else was working, I'd want to try it.
• My blood pressure has been a bit high in some of the most-recent Mayo visits, though it wasn't this time. I supposed that it should be a little higher for a person whose heart rate is low. The person needs as much blood as anyone else, and the heart doesn't have as many opportunities to pump it, so it has to pump harder on each beat, hence higher pressure. I was unable to convince her, though, because there are so many other variables and, as she said, blood pressure is more a function of the blood vessels than the heart.

Here are a few specific test results:

Test		Jul 24		Aug 22		Sep 16		Oct 16		Remarks
M-spike g/dL		1.1		1.0		1.0		0.9		Best tumor measure
IgG mg/dL		1360		1040		1180		1130		Variation is normal
L FLC mg/dL		3.30		3.57		2.64		3.14		Free light chains
Calcium mg/dL		9.7		9.3		9.7		9.6		Below 10.2 is best
Creat mg/dL		1.0		1.3		1.0		1.1		Kidney, lower is better
HGB g/dL		14.3		13.8		13.6		13.8		Hemoglobin, a bit low
RBC M/uL		4.17		3.99		3.90		3.97		Red cell count, low
WBC K/uL		4.7		4.4		5.3		4.4		White cells, normal

Red cell count and hemoglobin are on the low edge. I will continue to try to improve those numbers those with sublingual B-12 for another month, but it doesn't seem to make a difference.

Meanwhile I just ran another marathon and life is good.

The graph here shows results from 40, 20, 12, and 0 mg dex. Results from 20 mg (May) and 12 mg (Oct) are very similar, presumably because my system became more sensitive to dex in the interim. Click to enlarge.

Diabetic for a Day

Or two. DEX makes us temporarily diabetic by messing with the glucose transport system, which decreases the body's normal ability to move glucose out of the blood and into muscles and other organs.

I have a blood glucose monitor and did a simple study of my own blood glucose, taking a reading every half hour or so all day long, on four different sore-fingered days. Here is the bottom line result, where Day 1 is the next day after taking the DEX the previous evening. The "glucose" value is an average for the whole day, expressed in mg/dL:

Day	Dose mg	Glucose	Comment
1	40	144	Highest was 193
2	40	101
5	40	88	DEX effect must be gone
1	20	116

More information about this little personal "study" is detailed in earlier blog posts HERE and HERE. Graphics included. The graph here shows Days 1, 2, & 5 on 40 mg DEX.

I am NO expert in diabetes, but when Dr. L at Mayo saw the graphics and numbers for Day 1, she reduced my DEX dosage from 40 mg to 20 mg. The glucose spike of 193 mg/dL seemed to be a particularly important factor. Fasting glucose for a non-diabetic should be in the range of 80 to 120, and diabetics are urged to keep their glucose, fasting or not, below 180.

Many diabetics will need insulin shots along with a careful diet, but those of us who are not normally diabetic already have the insulin, except that its effect is inhibited by the DEX. Therefore we need to manage our temporary DEX-induced "diabetes" at least partly through diet. When I asked Dr. L about this, she commented that several of her patients are eating a low-carb diet on DEX day.

Here is a set of dietary principles that I have recently been following, with the help of Sunshine and Sweet Pea (they're the cooks!), on DEX day 1 and, to some extent, on Day 2:

• Most important: Keep the amount of food modest, because all food raises blood sugar. I do this with Weight Watchers "journaling," but calorie counting would work too;
• Reduce carbohydrates in favor of protein, and good fats such as nut oils, olive oil, and fish oils;
• Prefer carbohydrates with a low glycemic index, to reduce the glucose spike;
• Eat some of the protein and fat first at each meal, because this slows the entire digestive process and thereby moderates the glucose spike;
• Good food: Chicken, fish, vegetables, nuts, eggs, certain fruits and berries, legumes, whole-grain foods; and
• Bad food: Sugar (except fructose), soda, potato, candy, white bread or any relative, (the list goes on).

One caution: People whose kidneys are already at risk should be careful about increasing protein, and every myelomiac should take plenty of fluid to help the kidneys. As always CONSULT YOUR DOCTOR! But don't settle for "oh, don't worry about it." This is real, and somewhat outside the experience of many oncologists. Know what you are talking about, be your own advocate, and press a little. If you're interested, a blood glucose monitor costs between $30 and $100 with supplies.

You might notice that the foods that we eat on the DEX diet are foods that are really good for us anyway, and delicious. Those that are bad are ones that we never eat, ever. We just tilt the balance of protein, fat, and carbohydrates. So except for the protein issue for those with kidney disease, there is no downside to eating like a diabetic for a day or two. The food can be wonderful!

I wholeheartedly invite your comments, pro or con, and I especially hope that you will straighten me out if I have made any errors, or share with us if you have something to add.

Examples of DEX day meals that I have recently eaten. Oh, the suffering that we put ourselves through :-)

Today's DEX lunch: Organic chicken breast, Jim's broccoli, dill cheese, organic strawberries. Weight Watchers points = 6.


Today's DEX salad: Organic romaine, cucumber, avocado, organic cashews, organic strawberries, pecans, organic red wine vinegar. Weight Watchers points = 6.


Yesterday's DEX dinner: Wild-caught Alaskan sockeye salmon, organic lime, Jim's organic beet greens, spinach, and onions, with a few organic raisins, plus orange and mango. Weight Watchers points = 8.

Dex and Blood Sugar, Part 3

In early April I did a little experiment, measuring my blood glucose approximately every half hour on three different days: (1) Dex day (after taking dex the night before), (2) the next day, and (3) the fifth day (hopefully no dex). Results are here.

I didn't like that much dex for several reasons, and when I showed the shart to Dr. L she reduced my dex dosage from 40 mg to 20 mg. This week I did the measurements again for "dex day," and found the glucose levels significantly lower, as expected.

Here are averages for each of three different days:

Dex		Glucose mg/dL
40 mg		144.3
20 mg		115.8
None		88.2

Bottom line: 20 mg of dex puts the average glucose approximately midway between 40 mg of dex and no dex. Huh - no surprise.

Here is a TABLE showing actual measurements and times.

Below is a chart. Click to enlarge.

Dex and Blood Sugar, Part 2

Well, this experiment is complete, or as nearly so as it will get. I took blood glucose measurements on three days: (1) Saturday, after taking 40 mg of dexamethasone Friday at bedtime; (2) Sunday, the next day, and (3) Wednesday, the fifth day. Here are average blood glucose measurements for the three days:

Sat:		144.3 mg/dL
Sun:		101.2 mg/dL
Wed:		88.2 mg/dL

Bottom line: Assuming that Wednesday's measurements were "normal," then Sunday's were at least 10 points higher than normal and Saturday's were more than 50 points higher! This is "low-dose" dex - it's no wonder that high-dose dex gives people the symptoms of diabetes and sometimes even gives them the real thing.

Here is a TABLE showing actual measurements and times. It also has links to photos of the meals that were eaten.

Below is a chart of the same thing. Click to enlarge.

Dex and Blood Sugar, Part 1

We myelomiacs are all aware that dexamethasone (dex) can cause type II diabetes, sometimes permanent and sometimes reversible after discontinuing dex. This is most common among people who have taken "high-dose" dex, typically 40 mg per day four days on and four off.

I am taking "low-dose" dex, 40 mg once a week, Friday night before I go to bed. Nevertheless I already have a blood glucose monitor which I bought for another reason (not diabetes) and wanted to see what happens to my own blood sugar when I take dex. I decided to take a measurement about every half hour between waking and bedtime on three days: (1) Saturday, the day after taking dex, also called "buzz" day; (2) Sunday, "recovery" day; and (3) Wednesday, the fifth day, when effects from dex should be minimal.

The graph will be much easier to read if you click on it to enlarge it.


Here is a table with the actual numbers, exact times, and comments.

This experiment is only two thirds complete, but already somewhat instructive. I couldn't wait to post:

• About two years ago I ran a similar experiment for different reasons, and got an average reading of 104 mg/dL over parts of three days.
• Saturday's average reading was 144 mg/dL, much higher.
• None of my readings quite reached 200, which some say can be a signal of diabetes.
• Sunday's (today's) average is 101, even with big meals, much lower than Saturday.
• Glucose pretty much went up after eating carbohydrates, then down again, but with a few surprises:
  • The highest Saturday spike, 193, was measured shortly after finishing a big oatmeal breakfast with fruit and juice.
  • Later, a large serving of homemade chocolate fudge pudding, about 270 calories, seemed to raise glucose by only about 10 points. Are chocolate and milk able to slow absorption of sugars?
  • Still later, a slice of gluten-free bread with honey seemed to raise glucose by about 20 points.
  • All but one of Sunday's readings were lower than the lowest reading of Saturday.

I'll post about this again after Wednesday's test.