The Other Medications

I've written a lot about the Mayo Clinic & Celgene CC-4047 trial in which I am a participant. The major ingredients are CC-4047 (pomalidomide) and dexamethasone (DEX). But there are other drugs as well, that I haven't said much about:

• Aspirin, 325 mg daily.
• Acyclovir, 400 mg daily.
• Zantac (or generic ranitidine) with the dex.

Doctor L recommended all of these but didn't actually give me prescriptions, though I'm sure she would have if I had asked. The only one requiring a prescription is acyclovir, which is prescribed by my local internist.

Aspirin:

Recommended: 325 mg daily. I actually take two enteric-coated 81-mg tablets every morning with the acyclovir, and two more every evening with the CC-4047.

Aspirin reduces the likelihood of a deep-vein thrombosis (DVT). Both CC-4047 and DEX increase the probability of a DVT, and it is serious business. In my initial consultation with Dr L, I mentioned that when I was on thalidomide I had a pain in my calf, but I took a couple of aspirins and it went away. She leaned toward me, looked me straight in the eye, and said "YOU SHOULD NOT BE SELF-MEDICATING FOR A DVT!" Gulp. I guess I won't. The reason is that a DVT is a blood clot which can detach and travel to the lungs or the brain and cause heaps of trouble.

Aspirin can cause gastrointestinal ulcers. An enteric coating keeps the aspirin from being released until the tablet reaches the small intestine, where it is less apt to do harm. Most aspirin these days is enteric coated, which means that it is safer but does not work as rapidly.

In a recent presentation at a local support group meeting, a nurse told us that the amount of aspirin isn't critical. She said that aspirin has its effect on platelets, and once a platelet has been touched by aspirin it is changed and doesn't need more aspirin. Ever. Of course platelets die, and new ones are born, so daily aspirin is still necessary. I haven't googled this issue - just passing it along as if it were true.

A few months ago I asked my internist to do a coagulation check because of what I perceived as a bleeding problem. He did an INR and two other tests, but the results were perfectly normal. I was on daily aspirin at that time, same as now, so that's cool.


Acyclovir:

Recommended: 400 mg daily. I have a prescription from my internist for one 400-mg tablet daily.

Acyclovir is the generic name for an anti-viral medicine used to treat, among other things, various forms of herpes infections. In this case it is herpes zoster, also known as shingles, which can show up when a person's immune system is compromised, if that person has ever had chicken pox. I have.

Both CC-4047 and DEX can mess up the immune system. In fact DEX has a known and direct negative effect on the immune system. CC-4047, on the other hand, may enhance the immune system in several ways, at least as to the immune system versus myeloma cells (malignant plasma cells). Indeed, CC-4047 is known as an "immunomodulatory" drug, because it modifies the immune system. But CC-4047, like its relative Revlimid, may also decimate white cell counts, thus reducing the effectiveness of the immune system against herpes zoster.

While the normal use for acyclovir is to treat actual herpes outbreaks, daily acyclovir can inhibit some outbreaks and can reduce the intensity of outbreaks that do occur.


Ranitidine:

Recommendation: Dr L actually suggested either Zantac (ranitidine) or (I think) Prilosec (omeprazole), but my notes only seem to include Zantac. That was nine months ago, and now I don't remember why we didn't discuss Prilosec. She suggested taking a Zantac in the evening when I take the the DEX, and another the next morning when the DEX is having its maximum effect. There are two different strengths of ranitidine, 75 mg and 150 mg. I actually take generic ranitidine 75 mg tablets, one in the morning before DEX, one with the DEX, and the third the morning after DEX.

Ranitidine inhibits stomach acid production and is intended to treat heartburn. It should be taken 30 to 60 minutes prior to eating the food that would otherwise cause the heartburn. It has another beneficial effect, however: by reducing stomach acid it reduces the likelihood of gastrointestinal ulcers. DEX can contribute to ulcers, but the ranitidine may balance out that effect.

Omeprazole is a different kind of drug, called a proton pump inhibitor (who knew we have proton pumps?). It works more slowly, and I'd probably have to start at least a day in advance of the DEX, and take it for three or four days. I do get a very slight nausea from the ranitidine, so I might try the omeprazole some time, but not until I discuss it again with Dr L or her surrogate KDS.

Come to think of it, I should also ask Dr H, my naturopath, about ways to reduce the intestinal stress that causes ulcers.

I also take a slew of supplements.

The best web site for information on supplements is Margaret's Corner.



Salad & Dinner: Organic romaine lettuce, cucumber, boneless no-hormone no-antibiotics pork chops, organic cheese curds, avocado, Danish blue cheese, kiwi, filberts, organic broccoli, organic red wine vinegar.

Stable, With Caution

December 11, 2008:

My myeloma is stable after Cycle 10 of the CC-4047/Dexamethasone trial. Cool. But watch out for elevated liver enzymes AST and ALT.

This particular 28-day cycle may have been affected by several unusual circumstances:

• First, I really did take the supplements almost every day;
• I got a flu shot in mid-November;
• We enjoyed two days of Thanksgiving partying;
• Three weeks ago I pulled a band-aid off the back of my hand and unknowingly lifted the skin right off with it, leaving a large open sore;
• That sore developed a large (ugly) scab;
• Which does not look infected, but is healing very slowly;
• I got a 24-hour flu or food poisoning nine days before the Mayo appointment, including stomach upset and a slight fever, with a complete recovery by the next morning; and
• Something, who knows what, has caused liver enzymes ALT and AST to be elevated. ALT was 87 U/L, with a reference range of 7-52, and AST was 69 U/L, with a reference range of 15-37.

The Mayo test results don't indicate much change in the cancer numbers. M-Spike, the most significant number, is 1.0 g/dL, same as last month. In fact it has not changed much since August, the first time it dropped as low as 1.0. IgG is up from 1170 mg/dL to 1260, but for good reason, see below. Free lambda light chains are up 24% to 4.03 mg/dL, but kappa chains are up even more and the ratio actually went up a bit, so free light chains are probably not really up. The only scowl in the group photo is the elevated liver enzymes. Other blood numbers like red cells, hemoglobin, and platelets are as expected, with white cells and neutrophils increased as one might hope in response to a flu threat.

I go to Mayo every 28 days. I meet with Dr L every other time, otherwise with nurse practitioner KDS. This time it was Dr L. Here are a few subjects that came up:

• The increase in IgG might easily be attributable to the flu episode, because the immunoglobulins produced to battle the flu could last weeks in the blood.
• Similarly, the increased free lambda light chains could be coming from those plasma cells that produced the extra IgG. I think that's what she said.
• Dr L did not suggest a possible reason for the elevated liver enzymes, except maybe the flu episode. Especially if that was actually food poisoning and not flu. There was a now-suspect cheese ball ...
• Happily, two other liver markers are NOT up. Bilirubin was one of those, and I don't remember the other. LDH can be a liver marker but she didn't do LDH this time.
• The only albumin measurement this time was the one that comes as a part of the electrophoresis tests (with M-spike), and she doesn't quite trust that albumin result.
• However, that albumin result was UP to 3.6 g/dL from 3.4 the month before. It's a liver marker too, and UP is the preferable direction for albumin, trustworthy or not.
• In any case I will have the liver enzymes checked again in two weeks, the day before Christmas. If they are still up, it will probably be a dry Christmas for me. No beer. Sigh.
• I asked Dr L if there is any therapy for skin - some way to toughen it. She didn't know of any.
• Perhaps this is more the domain of Dr HH, the naturopath. Time for another appointment with her?
• People (more than one) have actually suggested Mayo Clinic's "Vanicream" skin lotion to strengthen skin. So we bought a couple of jars of that before returning home. I'll try it, what the heck.
• For what it's worth, the first ingredient is purified water, the second is white petrolatum, and the third is cetearyl alcohol. That third item is described in Wikipedia as not an 'alcohol' like rubbing alcohol, but rather a moisturizer, emulsifier, and stabilizer.
• She did suggest the use of heat to help heal the injury on my hand. I had been doing that in the beginning, with a glove to keep the area warm, but it's a good idea and I will try to wear it more faithfully.
• Dr L produced a chart on the computer that showed how CC-4047 (pomalidomide) stimulates the immune system in far more ways than thalidomide does.
• In contrast, dexamethasone suppresses the immune system.
• Yet the two together are more effective than either one alone. "Go figure," said Dr L. I guess there is more to be learned.
• Also, she believes that CC-4047 is strongly antiangiogenic, which means that it suppresses the creation of tiny new blood vessels. I got the impression that it exceeds thalidomide in this characteristic. Maybe Revlimid too. (CC-4047, Revlimid, and thalidomide are analogous immunomodulatory drugs.)
• We think that dexamethasone and other steroids are a cause of thinning skin.
• We also know that skin is constantly replenishing itself, wearing off from the outermost surface and rebuilding from below.
• I wondered if the rebuilding of skin might require the creation of tiny blood vessels, and if so, CC-4047 might interfere with the creation of new skin. She said that she always thought of the dex as the culprit in thin skin, but didn't discount this possibility either.
• Perhaps this could also account for the very slow rate of healing of injuries.
• Now I wonder if any other bodily organs might suffer from lack of an ability to rebuild. Does the heart rebuild itself? Lungs? Liver?
• I didn't discuss this with Dr L, but I notice that ALT and AST have been elevated before, in 2003 and 2004. Back then I believe that we attributed the temporary increase to running. I did a 5-mile run Wednesday night, less than 12 hours before this most-recent blood test. Could that be the cause? I'm thinking maybe so.
• The drive to Mayo is 90 minutes, and she gave me permission to drink black coffee on the way from now on, even though the first business on arrival is a blood draw. I will appreciate that.
• Of the 60 people in the CC-4047 trial, most are responding, including several for whom Revlimid has failed.
• One patient in particular was refractory to everything including Revlimid and Velcade, yet had an excellent response to CC-4047.
• Only two of the 60 patients are now progressing again.
• The generic name for CC-4047 will be pomalidomide, but the trade name will NOT be Actimid. Don't know what it will be.

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."

Other 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		Sep 16		Oct 16		Nov 13		Dec 11		Remarks
M-spike g/dL		1.0		0.9		1.0		1.0		Best tumor measure
IgG mg/dL		1180		1130		1170		1260		Variation is normal
L FLC mg/dL		2.64		3.14		3.25		4.03		Free light chains
Calcium mg/dL		9.7		9.6		9.8		10.1		Below 10.2 is best
Creat mg/dL		1.0		1.1		0.9		1.0		Kidney, lower is better
HGB g/dL		13.6		13.8		14.6		14.6		Hemoglobin, normal
RBC M/uL		3.90		3.97		4.19		4.20		Red cell count, low
WBC K/uL		5.3		4.4		4.3		5.3		White cells, normal

I'm still running 20 miles per week, getting set to increase that gradually back up to 40. Life is good.


Oatmeal breakfast: Gluten-free oatmeal, blueberries, organic walnuts, organic plum, organic low-fat milk, Dove dark chocolate, and "kiwi berries." We had not seen kiwi berries before. They are smaller than a kiwi with a nice, edible skin, and taste just like kiwis. Not organic, but we tried 'em and liked 'em.