Thursday, December 31, 2009
If you want to make some 2009 donations to further the cause of CLL research, please consider the following organizations:
Perhaps you remember the research effort into finding the antibody which may wipe out all CLL cells? That effort excited Dr. Byrd at Ohio State and a CLL guru. The sooner we get this in trials, the better. The address for donations is:
The National Cancer Institute Gift Fund, Building 31/Room 11A-16, 9000 Rockville Pike, Bethesda , MD 20892 . The check should be made out to the National Cancer Institute and the cover letter should request that the donation be used to support translational CLL research such as that conducted by my laboratory.
The other organizations that help support CLL research include Dr. Kipps' Blood Research Fund:
Dr. Keating's CLL research fund is at:
The Kanzius machine that may help treat CLL is being tested at MD Anderson. It uses nanoparticles to attach to CLL cells; heat is then applied body-wide to destroy the cells.
PLEASE PLEASE PLEASE donate to destroy CLL. We need a cure NOW!
And, please all of you one or two people reading this, have a safe and healthy New Years Eve and the same for all of 2010. May this be the year CLL is cured.
Saturday, December 26, 2009
I am having continuing problems with my gut, bloating, gas, etc. etc. I don't know whether I have an infection or this is the result of the Alvocidib (flavopiridol). I am going to the urgent care clinic to find out this morning. It is troubling and very painful.
Be well, all.
Friday, December 18, 2009
Perusing the ASH abstracts, a number of papers caught my eye, including this one: http://ash.confex.com/ash/2009/webprogram/Paper19496.html. The authors say that “Myelodysplastic syndromes (MDS) are becoming the most commonly diagnosed forms of leukemia in the US .” Also, consider this very interesting paper that asserts that MDS may be afflicting over a hundred thousand Americans: http://www.moffitt.org/CCJRoot/v16s4/pdf/2.pdf
One reason MDS might be increasing in frequency is that it can arise as a result of chemotherapy for other cancers, including fludarabine-containing regimes such as FCR for CLL. As cancer patients live longer (always a good thing, of course) other cancers will make their presence known, unfortunately.
Saturday, December 12, 2009
It's difficult in San Diego, because the water is the worst-tasting water I can remember ever trying to drink. Bleech!
I have been thinking about taking some flavored powder to add to the water. I know the importance of staying hydrated, and any help killing the taste would be welcomed.
This is from Yahoo.com
Cities with best and worst tap water
By Lori Bongiorno
Posted Sat Dec 12, 2009 10:55am PST
More from The Conscious Consumer blog
How safe is the water that flows out of your tap? The answer very much depends on where you live.
It's now easier than ever for consumers to find out what's in their tap water. The Environmental Working Group (EWG) today released the results of a three-year investigation of municipal water supplies across the U.S.
The research and advocacy group looked at water quality tests performed by water utilities since 2004 and created an extensive database that contains info on the contaminants found in 48,000 communities in 45 states.
EWG also rated 100 big city (population over 250,000) water utilities. Below are the top and bottom results.
Cities with the worst water:
1. Pensacola, FL
2. Riverside, CA
3. Las Vegas, NV
4. Riverside County, CA
5. Reno, NV
6. Houston, TX
7. Omaha, NE
8. North Las Vegas, NV
9. San Diego, CA
10. Jacksonville, FL
The article suggests the water isn't particularly safe. I don't know about that, but I can tell you the water just tastes terrible.
Saturday, December 5, 2009
As my rare reader probably knows, I started on a phase II clinical trial of Alvocidib (flavopiridol) in late July. I'm a bit more than half-way through the trial, which, if I make it that far, will last nine months and end in the latter part of March, 2010. (An aside: I wonder if this change in the year will FINALLY cause people to stop saying the year in the most ridiculous manner possible, i.e. two thousand and nine instead of the proper, twenty-oh-nine. Correct me if I'm wrong, but did we say, for example, 1998 as one thousand, nine hundred and ninety eight? I don't think so...)
I get a weekly blood draw; when I'm in San Diego, it's through my port, when on my infrequent trial holidays, it's through the veins in my arm here in Sacramento. I noted a trend about a month ago that my platelets were up a bit. I've been running below normal in my platelets since about 2003. Nothing major, but they've oscillated up and down between 55 and 95, usually hanging out around 70-80. My count on October 9, 2009, for example, was 82. This is not a dangerous place to be, but I don't go skydiving or race cars as I don't what a subdural bleed. No siree!
The last three blood tests in November, the last two done here in Sacramento, show the improvement continues. My 11-12 test shows my platelets were at 95. On 11-18, they topped 100 for the first time in many years at 101. My November 25 blood draw had the platelet numbers at 134, the first time it has been in the normal range, as I've said, in many years.
I can only guess this is the doing of the flavopiridol. None of the other treatments that I can recall worked so well on platelets.
Obviously, I'm pleased.
And while this happy situation won't last forever, and my number will likely slink back to the less happy situation of low platelets and increasing tumor burden, today, I will make the most of it. I was thinking that I don't have to have any real worries about shaving, getting cut, having nosebleeds, bleeding profusely at the slightest nick, and so on. I might even take a fish oil tablet for the heck of it, since heart disease runs in the family, and I now have enough platelets to clog an artery or two.
The other numbers are still in the abnormal range, though the hemoglobin has been above 10.0 for over quite a while, at least out of the danger range for well over a year (I've had to have blood transfusions on a number of occasions - thank you blood donors!!!).
So the platelet counts are fab, and I'm thankful for that. I still have CLL cells everywhere, but they have been beaten back for the time being. And in spite of those bureaucrats, especially in socialized medicine England, who say six months of extra life if just no big deal, I will tell you that my decent health since I've started flavopiridol is priceless to me.
Friday, December 4, 2009
Being the patient, I can say that I will not protest too much that I get a two-week break. Part of the procedure using flavopiridol is that one cannot have too high of a potassium level. I've discussed this before, but the dying CLL cells dump the cell contents in the blood, and this can cause acute renal failure which has been fatal in at least one patient in the phase I component of the study. Starting off with a low normal level of potassium (3.9 or thereabouts) means that there is room to go up without doing anything drastic in terms of managing the potassium level.
So, I try to manage this by drinking lots of water spaced throughout the three days before going down to San Diego for the next infusion. (There is a danger of drinking too much all at one time. Search on 'water intoxication.') I also go on a low potassium diet, which I have devised. This is basically a 'white' diet consisting of white bread, white cake, white cookies, muffins, etc. Few vegetables and no meats are low in potassium. Also, no chocolate. The 'diet' is more comprehensive, of course. And, of course, don't do anything without checking with your doctor as I have.
This means that my diet is severely restricted for the Sunday, Monday and Tuesday before the Wednesday infusion. (I fast on the day of the infusion because anything I eat will just come up later. And I will have an aversion to that food for a long time. As it is now, the thought of raspberry juice is revolting, since I used to buy a raspberry Snapple and wash down pills with that. Bleech! Sorry, Snapple.)
So...I can have a normal diet for Friday and Saturday. Only two days a week. Of course, things could be a lot worse.
Anyway...I had a wonderful two-week break the last two weeks of November. This included Thanksgiving. My wife is a great cook and we had a turkey breast (thank you mister or miss turkey for giving up your life for my meal) with the usual fixings. I had Thanksgiving and the day after off from work, so my wife and I spent one day up in the foothills of the Sierra poking around various antique shops.
We try to do two trips a year in Amador City and Sutter Creek. These two are delightful towns that are only 30 miles from Sacramento, but with a totally different feeling. It's a beautiful drive up highway 16 east of Sacramento, then south on highway 49. It's especially pretty in the fall with the changing leaves on the trees, the cold air, the wood smoke in the air, and the happy tourists clogging the streets.
We spent the day looking at and for various fun things to look at or to buy. Sutter Creek has a crafts fair most weekends from Thanksgiving to Christmas. Both towns have some unique shops that carry things you don't ordinarily find. My wife's favorite shop is in Amador City, and features antique lace. Now, as a guy, I don't know why anyone would want to wear 100-year-old fabric, but my wife puts together some attractive looks mixing old lace and modern clothes.
It may not be the best way to administer the flavopiridol, but having a two-week break from the tedium of flying to and from San Diego, and spending the day in the infusion room isn't all bad from my point of view!
I'm more than halfway through the regime. So far, it has been working pretty well.
Saturday, November 21, 2009
Well, I won't have any part of it.
I have avoided any television and radio broadcast of the NFL this year. Withdrawal, as you might imagine, isn't difficult, especially with the panoply of college games on the boob tube. I enjoy football, I enjoy watching the plays and the strategy unfold, and I find the college game to be more rewarding than the pro version.
For many decades, college football was the only game in town. The pro league was an afterthought watched by dozens of fans every year. I don't know why it changed; I suppose a case of severe laziness on the part of Americans. Not only can they watch college football on Saturday, but they can (if they support dog-killers) watch the pro version on Sunday, Sunday night and Monday night.
I have to confess I enjoyed watching the pro version if my team, the San Francisco 49ers, were playing. The 1980s teams with Joe Montana were almost all-consuming on Sundays. If I were going to be out of town (I used to hike on Sundays frequently), I'd tape the game, every last game.
I must say I don't miss the pro version at all. The 'crutch' of college football has helped ease my withdrawal, and, to be fair about it, the pro version only lasts five or six months of the year anyway. So I've had to suffer the withdrawal every year for six months, anyway.
And there is always baseball. Baseball is the best game to listen to on the radio. You don't have to watch the plays, since there is only one or two players involved in most plays (unlike football where there are 22 players on the field, most of the time). And baseball lasts seven months, plus there are the exhibition games when it's also fun to listen to. Baseball is kind of boring to watch on television; radio or live is the best.
All in all, let the NFL celebrate dog torturers and play with their over-paid players, over-paid coaching staff, and maniacal owners fiddle around with their delusions of grandeur. I'm not part of it, anymore.
Friday, November 20, 2009
I noted an interesting editorial from Dr. Byrd on the discovery by researchers of the National Institutes of Health of a single antigen on CLL cells that may be common to all CLL cells. (An antigen is a protein that is the target of an antibody.) Dr. Byrd practically gushes with enthusiasm for the possibilities for CLL and other blood cancers from this discovery (http://bloodjournal.hematologylibrary.org/cgi/content/full/114/20/4324). In fact, his editorial is entitled, “Hunting for the Achilles’ Heel of CLL”. He terms the value of the process in identifying the antigen common to CLL cells as ‘immense’.
That sound like extremely good news!
What the researchers did was to look at people who were cured of their CLL by allogenic stem cell transplants (SCT). They then compared the blood to the patient’s blood and CLL cells that were preserved from the time before they had their transplants. (Research such as this is the reason donating blood for research is so important.)
Using sophisticated techniques, they were able to identify an antibody to an antigen that was present on the CLL cells in these patients before their transplants. The antibody wasn’t present in the patients (otherwise they presumably would have never developed CLL in the first place), but was produced from the donor’s stem cell derived B lymphocytes. It appears that, once the donor’s stem cells start producing those lymphocytes in the transplant patient, somatic hypermutation (which is the process where by all antibodies are produced by the body), starts working to produce an antibody which then starts to destroy CLL cells.
Byrd envisions development of this work to leading to therapies that may improve the curative potential of stem cell transplants. He also suggests that this may find a place in non-transplant therapies in treating CLL and other blood cancers. Avoiding the very expensive, very complex, very disruptive, and dangerous STC would be highly desirable!
Saturday, November 14, 2009
As I've mentioned before, there is some thinking that as long as the drug is working, why stop it for two weeks every month? I concur with that thinking, especially if a continued pounding of CLL would conceivably result in a cure. However, flavopiridol has, per the latest published results of the trials (http://tinyurl.com/yhhp286) using the drug, only resulted in one complete remission. The over-all response rate was 53%, most of which were partial remissions. There was one complete remission in this study, which I've not read has occurred in previous studies.
And I must admit the two-week holiday is something to look forward to. It would be different if I lived in San Diego, but I don't.
My own experience is that I have responded to the drug. My main complaint prior to enrollment in the trial was large abdominal lymph nodes. I was doing my best to treat the lymph nodes with 3 mg per day of EGCG (the green tea component) and what ever else I could think of (curcumin, PEITC through watercress, vitamin D3, exercise, etc.) Eventually the lymph nodes elsewhere in my body, which had remained very quiescent, started growing.
My blood numbers have remained quite low since my sad experience with FCR, so low, in fact, that I worry I may never recover what passes for normal bone marrow function in a CLL patient.
My lymph nodes (especially abdominal) have been my greatest complaint.
After three cycles of flavopiridol, what have I learned? This is not a terribly easy drug to take, although I have learned how to mitigate many of the side effects. The first problem is the terribly ill feeling I get the evening after getting the drug. I feel very sick, very nauseated, often vomit, have persistent diarrhea, and just plain feel terrible. I have an elevated heart rate as well. It is all I can do just to get into bed and ride it out. Several times I have felt so unwell that I had to go to the emergency room.
To counter the nausea, I've insisted and insisted on adequate anti-nausea medication, which is surprisingly difficult to get. I guess everything that is given on a clinical trial has to be per the protocol, or you don't get it (exceptions of course are made; people don't die because life-savings drugs aren't on the protocol). I take ativan prior to the start of the flavopiridol, and get injectable zofran. This helps; I also have ativan and zofran to take if I feel nauseated later in the day.
The diarrhea is a problem, since I fly from San Diego back to Sacramento the day after getting the drug. After some experimentation, I use Immodium at the first sign of problems, and I take yogurt for the probiotics after I get back home. This (so far) had made the problem more mild.
The fatigue is something all CLL patients are used to; you just rest and do what you can do. It only lasts for the rest of the second day. By the third day, I'm back to the generally low-level of energy which accompanies CLL.
As I mentioned in the last post, I avoid the diarrhea-inducing medicine at all costs. Just thinking of it, or seeing the bottle, or remembering the taste makes me ill and wanting to vomit. Bleech! So I go on a low-potassium diet for three days before the treatment; this has kept my potassium level below the magic 4.0 so far. However, this is a very restrictive diet; I have created a chart of a variety of foods with their potassium levels. This means no fruits, nochocolate, no potatoes, no tomatoes, no soy, no milk, no bananas, no meats of any kind, no carrots, no raisins, no yogurt, no bran, no multi-grain breads, no nuts, no orange juice, no beans, and so on.
You are allowed white bread, white cakes, white cookies, rice krispy bars, water, oils of any kind, and small portions of cheese, iceberg lettuce, olives, pasta, and most soft drinks. But it is worth it to avoid the diarrhea-producing drug!
So, at this point, both Dr. Kipps and I are satisfied with the results. Flavopiridol can work on heavily-pretreated patients with unfavorable prognostic indicators, such as me. Thank God (and the researchers and the pharmaceutical industry)!. Otherwise, who knows where I'd be right now...
Sunday, October 11, 2009
Flavopiridol, also known as Alvocidib, is a cyclin-dependent kinase inhibitor. It has been suggested that it helps promote CLL cell apoptosis, or programmed cell death; it also slows the growth of cancerous tumors.
The drug has an interesting past. It was discovered to have a very profound CLL cell killing effect in the test tube, but when tested in humans, it seems to have no effect at all. The drug was set aside, but 'rediscovered' and looked at again. It seemed hard to believe it could blast CLL cells in the laboratory, yet do nothing in patients. Finally, they figured out that the drug would bind to human serum proteins, leaving precious little available to kill the cancer cells.
After much more experimentation, a different dosing schedule was worked out. The drug is now given in two stages, one dose to bind to the blood proteins, and another to go in an hour or so later, in hopes it will kill CLL cells.
I started on the trial in late July. The clinical trial calls for the drug to be given once a week for four weeks, then a two week 'holiday'. Theoretically, this regime could be given for up to nine months, as long as the disease doesn't progress or the side effects aren't too terrible.
(Dr. Kipps told me he doesn't understand the need for the holiday, since the drug is not myelosuppressive (i.e. it doesn't cause damage to the bone marrow or lead to depressed blood numbers)).
The first two times are down with a hospital stay. This is precautionary since there have been deaths associated with the drug. The cause of death is massive cell death, or tumor lysis syndrome. The massive cell death can dump cellular products into the blood that overwhelm the kidneys, leading to acute renal failure. It is my understanding that the first patient treated with flavopiridol died from renal failure.
The stay in the hospital allows for a quick hook-up to a dialysis machine if tumor lysis syndrome occurs. This did not happen to me. Instead, they managed the blood numbers (they primarily focus on the potassium level) by inducing diarrhea. I can attest that the drug they use to induce diarrhea works very well. I was up and down on the pot about 35 times the first stay in the hospital (my poor roommate was pretty much locked out of the bathroom).
After the first two weeks, the patient is treated in the infusion room.
So far, I've had two stints of four infusions each. The treatment has worked well; my blood numbers haven't changed much, so there is no impact there (although my blood numbers have been very low since my disastrous acquaintance with FCR). The main benefit has been in my spleen and abdominal nodes. I've had shrinkage in the massive nodes in my abdomen and in my spleen.
The main adverse side effect has been my development of a severe aversion to the diarrhea-inducing medicine. I cannot tolerate the taste, the smell, the sight or the thought of this drug, (Kayexalate). I started to get sick after taking this about the fifth time, and I ended up in the hospital vomiting for an hour or so.
What I do now (and I REALLY wish I had know this going in) is to go on a low-potassium diet on Sunday before my Wednesday infusion. If you have a level below 4.0, they won't force this vile stuff on you. So I am VERY, VERY careful to have a low potassium level before I do the flavopiridol.
It is such a negative effect that I probably would drop out of the trial.
The other thing that they didn't do is routinely treat me with anti-nausea drugs before the treatment is started. Instead, they wait until I start vomiting. Dumb! Anyway, I now take my atavin and zofran with me and take it before I start on the treatment. The last time I was down there I only vomited a couple of times.
The other really odd side effect is what happens about four hours after the treatment. I suddenly feel terribly ill, ready to go to the emergency room with a fever and general malaise. However, it passes after a half hour or and hour. However, I am ready to call 911 if I have to.
So, flavopiridol seems effective, but is not the easiest drug to take.
Friday, August 28, 2009
This is disgusting. The monster Vick was not only involved in dog fighting, a brutal sport that by definition is animal abuse, but he tortured and killed dogs who weren't 'good enough' to fight other dogs. That means that innocent dogs who wagged their tails, licked hands and faces, full of love and happiness, were tortured by electrocution, by strangling, and by being stomped to death at the hands of the monster Vick.
Yet this monster is glorified by the NFL and the residents of Philadelphia? This evil monster is rewarded by the NFL, the Philadelphia Eagles and the fans of that team?
I cannot watch a NFL game as long as the monster Vick is rewarded by the NFL. I will not watch a game, I will not watch any pre-game show, I will not buy anything from any advertiser that I know of that pays the NFL and/or the Philadelphia Eagles, nor will I allow the evil that is associated with the monster Vick into my home.
It is indeed sad that America not only allows such evil to get out of prison after only 18 months, but it REWARDS the evil that the monster Vick is.
I will never set foot in Philadelphia as long as I live, for the citizens of that town encourage and love all that the monster Vick represents. If they objected, the monster Vick would not now be playing for the Eagles.
I know my actions will not change the venality of the NFL or the Philadelphia Eagles, but I hope somehow the poor dogs who suffered terribly at the hands of the monster Vick know that someone loves them and is so sorry that they suffered. I hope somehow they know that someone fought to deny their torturer the rewards and adulation that Philadelphia is showering on the monster Vick.
Thursday, August 13, 2009
The complete remission rates of FCR, reported primarily out of MD Anderson, are extremely impressive, and far exceed that of chlorambucil. For example, at the 2007 ASCO meeting (American Society of Clinical Oncologists, a major cancer group), MD Anderson reported on the long-term results of 300 patients who were treated with FCR at the institution. The group reported that 72% of patients enjoyed a Complete Remission, 11% obtained a nodular PR (PRn) & 12% ended up with a Partial Remission. Saving the calculation, that is a phenomenal over-all response rate of 95%. In spite of the immune suppression associated with the drug combination, infections were manageable with prophylactic antiviral, antifungal, and antibiotic drugs.
However, the long-term survival pattern showed no plateau, meaning that the rate of death did not level off at any point, meaning that most if not all patients would eventually fail FCR. Quoting the study: "Median Times to Progression (TTP) were 80 months for CR (n=216), 80 months for PRn (n=32) & 27 months for PR (n=36), with 77%, 65% and 28% projected to be progression-free at five years; projected 5 yr survival were 90%, 81% and 37% respectively."
These data are superior to single agent fludarabine, and fludarabine in combination with cyclophosphamide (FC) or mitoxantrone (FM).
The down side? Well, it is not a cure, nor does it appear to have that potential. There are some very long-term survivors, out 10 years or more. But based on projections, it is possible, if not likely, that most everyone will eventually relapse. And even in the case of those who have deep, long-term molecular remissions (data not available in the 2007 ASCO abstract, but has been reported to be about 32% in complete responders, meaning the over-all MR rate is about 24%) it is expected that they, too, will fall out of remission down the line.
So, what will replace FCR as the 'gold standard'? It must be noted that this is a moving target. For decades, chlorambucil was termed the gold standard, even though complete remission rates were only about 5-10%. Then single agent fludarabine took that exalted spot.
I think that the best initial treatment for CLL might very well be high-dose methylprednisolone plus rituximab (HDMP+R). I had a discussion with a couple of nurses at UC San Diego, where Dr. Kipps has a great deal of experience with the drug combination, and they said they just don't use FCR too much any more. Instead, they do a lot of HDMP+R. I have to admit that off-handed comments by several oncology nurses isn't definitive proof, but it is very interesting that, at least in one institution, FCR has seemingly fallen out of favor.
So what does HDMP+R have going for it? For one thing, it doesn't damage the bone marrow like fludarabine does. Fludarabine has a deserved reputation for enhancing the fatal rates of infection for up to two years. This is due primarily as a consequence of prolonged neutropenia. Grade 3/4 neutropenia were encountered in FCR. That makes the patient much more likely to have a serious illness, or even death.
First developed as a salvage regime for those patients with refractory CLL (and still used for this application), patients were given five cycles of the drug combination. It was not for the faint of heart. Numerous infections occurred and deaths were reported. The regime was tailored for a less-impacted crowd; as an initial treatment for CLL patients. The duration of the regime was shortened to three cycles.
A report in 'Leukemia' 2008 reported that in patients who were refractory to fludarabine and had adverse genetics, fully 93% of patients responded to the combination, and 36% had a complete remission. This compares favorably to the FCR regime. The paper states that median survival "has not been reached after a median follow up of 40 months."
There are also anecdotal reports that some patients who have completed HDMP+R have begun to normalize their immune system, as reported in a previous blog post here. That is simply astounding to me; I am unaware of this happy development in anything less than a stem cell transplant.
It also should be noted that adding a Campath 'chaser' to those who responded to the drugs, and did not develop bulky lymph nodes, may have enhanced responses.
Another development in CLL needs to be reported as well: 'FCR-lite'. This regime seems quite promising, with good results in spite of the reduction of the dose of fludarabine and cyclophosphamide, and an increase in the dose of rituximab. Reports are that the side effects are lessened compared with FCR, and the responses seem to be (at least initially) almost on par.
The paper states: "The OR and CR rates were 100% and 79%, respectively, using the 1996 NCIWG guidelines and 100% and 77% using the 2008 guidelines. Median duration of complete response was 22.3 months (range, 5.2 to 42.5 months) and none of the complete responders have relapsed. Grade 3/4 neutropenia was noted in 13% of the cycles of therapy."
It must be noted this trial was in untreated patients, most of whom had early stage CLL (only 16% had stage 3 or 4 CLL). (I'm not sure why a stage 1 CLL patient was even treated, but 40% were here.) That might be considered 'stacking the deck', and making comparisons with FCR and HDMP+R difficult if not impossible.
The bottom line: It may be premature to dethrone FCR as the gold standard, but recent advances in research suggest that we might need to rethink exactly who's on top in caring for CLL patients.
Friday, July 31, 2009
This is big news. Of course, I don't know (and I don't think the researchers know) if this will hold up, or if the trend towards a revamped immune system will continue to total normalcy. However, as we've been often told, even in molecular remissions, the native immune system remains disrupted. This may not be the complete truth.
My feeling was from what he said was that this is in a minority of patients. But I think the true import of this development is that there may finally be some light at the end of the tunnel. I hope enough of a trend continues that a paper will be written that discusses these developments (if they remain developments) more completely. I look forward to the day!
Since infections kill most CLL patients, having a full-functioning immune system would be big news indeed.
Since this was an off-handed comment, I just don't know the particulars. However, I hope this does hold up. Certainly, this is another indication that research is extending lives. Is this an indication that, caught early enough, and treated properly with powerful, dangerous, but effective drugs, a cure might be possible?
Yes, a generous donor has made a challenge grant to the Blood Cancer Research Fund (yes, for CLL). So for every dollar you donate, another dollar comes from this fund and goes right to work!
Apparently this has been going on for a year, but I just read about it a few weeks ago, and haven't had time to post on it.
Seriously, folks, now is the time!
Please, rare reader, think about making a donation to Dr. Kipps and the hard-working team in CLL. I have heard from many others that cutting edge research is coming from the mind of Dr. Kipps and other talented people, all of whom depend on funding to further understand CLL.
I know times are tight, but as the article says, just $10 per month for the next year would match this grant.
(I'm not neglecting other funds myself, and I am not saying don't contribute to CLL research groups. I think right now, by doubling our donations, this is a very effective way of making our contribution go as far as possible.)
Think about it.
There are other indications for treatment as well. I must confess that I am basing my recommendation on my own experience and what I believe to be accurate. It is based also on the experiences of others and conversations I've had with people, those with a medical background and those who are just careful researchers, as well.
I confess I don't know if a reputable oncologist would initiate a watch and wait patient simply on the basis of reported increase in fatigue. Or with bothersome night sweats. Or on the basis of Rai/Binet stage alone.
I suppose I should really say that it is my opinion that if one is tracking one's absolute lymphocyte counts, and they make a radical change north (as mine did), it's a sign things are changing. People I respect have concurred with me. But, as I've said, this is not a complete picture. Perhaps it's only good for a subset of CLL patients. (But remember that night sweats and other 'B' symptoms aren't always related to CLL. Other diseases or even coming off drugs for pain can lead to this problem. Or, I understand, even menopause?)
Saturday, July 25, 2009
1. The first treatment is most likely to give the patient the longest and best response to treatment.
2. The CLL cells haven't been exposed to any treatment, and thus generally consist of nice, 'squishy', easy-to-kill CLL cells. None of your cells have been through 'chemo boot camp', thus aren't toughened up by 'combat'.
3. The patient generally is in as good of shape as he ever will be.
4. The choices for treatment are wide-open (all things considered). The oncologist can generally offer many different treatment modalities.
So, how can the patient decide when he needs treatment? Well, I suppose the simple answer is that he can't, at least by himself. He needs to do so with the assistance and the guidance of his oncologist.
At this point, let me make it clear that my perspective comes not from a medical background, but from that of a patient who has survived over 10 years with CLL, and, more importantly, have researched the topic in some depth.
There are two proven guides to when treatment might be necessary. One is the stage of your CLL (stage 0=1 is unlikely to need treatment, but it may). The second, and over-riding one to me, is the doubling time of the Absolute Lymphocyte Count (ALC). (The count is easy to derive: take the total white blood count, and multiply by the percentage of that count that are lymphocytes. In other words, if your WBC is 100, and your percentage that are lymphocytes are 90%, then the ABC is 90,000.)
You've probably seen a number of sites and posts which offer the ability to enter in data which will then produce a graph. Excel is spreadsheet which allows one to chart blood numbers, there are others as well.
Starting with the blood counts taken at diagnosis, I recommend creating a spreadsheet and entering at least two data sets: the absolute lymphocyte count and the day the blood was taken.
I've worked with a spreadsheet from scratch, but you don't have to do that. You can download a spreadsheet ready to enter your blood numbers from CLL Topics: www.clltopics.org/YourCharts.htm .
Once you have developed a worksheet, you can add to it with each blood test. Let's assume you have fairly stable absolute lymphocyte count (other data such as the total white blood count won't work). This is typical in early CLL. Plot each value, and pay attention to the trend. To make the trend more clear, create a chart using time as the x-axis and the ALC as the y-axis.
One tried and true indication that treatment might be in order is when the absolute lymphocyte count (ALC) shows a pattern that will result in the number doubling in less than one year. (Check with your oncologist to see if this is how he views treatment decisions.)
Once you start plotting data, thing those of you are going to need treatment will see an obvious jump in ALC. The trend must hold for some period of time, or over several tests.
It is at this point that something has changed in your CLL. Perhaps you have picked up a change that causes your CLL to start proliferating at a higher rate. Perhaps for some reason your CLL cells are not dying at the same rate they were previously.
In any case, I personally think this may mark the best time to hit your CLL.
The other indicator that treatment might be considered is your stage. If you are diagnosed with a stage IV CLL, you probably have noticeable illness in terms of a low platelet and/or hemaglobin number. I'd still chart out your ALC and share with the doc to see if the disease is making a move.
Tuesday, July 21, 2009
Suffice it to say, some of the barriers to entry of clinical trials are listed on the last post.
I want discuss one real barrier to clinical trial entry that is easily remedied. That is the demand that participants undergo multiple CT scans to track progress (if any) in the trial.
Why is there a barrier? CT scans involve high levels of radiation, and they have definitely been linked to subsequent cancers.
The risk is low, the authorities say. But any increase in cancer risk sort of defeats the search for a cure for CLL, doesn't it? It certainly makes no sense when there is an excellent alternative: MRIs.
Clinical trials are done to look for results. The ultimate hope is a cure, because the drug in tests would be a huge success! Most likely, a more modest goal is envisioned: better results than current drugs.
Determining whether a drug is better than the standard treatment is surprisingly difficult. Drug companies can't wait around for 20 years to see if patients continue to do well (i.e. survive). Instead, they look for 'end points'. These generally include signs of tumor shrinkage or elimination. That is the reason drug companies want to check your nodes. The way most doctors are used to doing this is ordering a CT scan.
Yet we've seen the danger to the patient is real. Given a choice between a trial using an MRI and one demanding multiple CT scans, most people who are aware of the dangers of CT scans will pick the safer one, in other words, the one allowing the use of MRIs.
Why do drug companies deliberately rig their trials so people are less likely to sign up? It's a mystery, with perhaps a partial solution. Several of the drug companies I've talked to are aware of the concerns on the part of patients, and know that an MRI can track lymph node size just as well (or better) than CT scans.
Well, who then is the moving force behind this unfortunate situation? The drug companies blame the CLL researchers themselves! It is the research community that apparently doesn't care about patient safety to the point that they will allow safe alternatives to dangerous radiation exposure to patients.
I've discussed this with a few researchers in light of these claims. Rumor has it that there is a group of CLL researchers who are (pardon the expression) really anal about scans. The Germans.
I suppose we who are not German can recall the reputation the Germans have for meticulous record-keeping and administration. It apparently extends to CLL clinical trials.
Who ever is to blame, it's time the patient community help end the danger. Some of us need clinical trials if we are going to stay alive. We are sacrificing our bodies to advance science. It is incumbent upon researchers to watch out for our health. We are helping them (and the drug companies) when we sign up for a trial. They need to help us avoid doing more damage to our bodies than the investigational drug might cause.
Monday, July 20, 2009
Any clinical trial needs two things: a new drug or device, and bodies to test them. Cancer, as one can imagine, is chock-full of new drug applications, and clinical trials. Go to the excellent site for the government's clearinghouse for clinical trials (clinicaltrials.gov), and you'll find about (about because it changes every day or so) 23,000 trials in the US and overseas that involve some aspect of cancer.
Some trials seem almost silly. There are, for example, a number of trials examining the value of music to soothe the savage cancer patient's breast. There are some that seek to find the value that art has in calming dying cancer patients.
Mostly, however, clinical trials seek to ascertain the dangers and values of drugs in fighting advanced cancer. (There are some trials, of course, looking at treating patients early in the disease; CLL is a particular hotbed of such studies, since previous research has not uncovered a value in starting treatment early, as opposed as to when it is most definitely needed.
Search clinicaltrials.gov for CLL trials and (as of this moment) 1209 trials show up. The site seems to list trials that only mention CLL in passing; there are far fewer trials that have CLL as the main focus of study. There are probably fewer than 200 that are of serious interest to the CLL patient.
So, should you enroll in a clinical trial? That is a tough question, but, over-all, I'd recommend you seriously consider it. Why? Because every effective drug for CLL has gone through the clinical trial process, and you'd have first (or second, or third) crack at it. When you have run out of options, that is not a small factor.
(There is also the altruistic nature of trials as well. By joining, you will help future CLL patients have access to proven drugs. But studies have shown that most participant hope to have some benefit as well).
Let's say you've decided to at least look at clinical trials. Are they all created equally? No, of course not. Unless Bach or Picasso really rocks you, you might just say no to music and art clinical trials. You are not going to get cured by such a trial. But what should you look at?
I'll give you my thoughts on the subject, but remember that I'm 'only' a CLL patient, one who has (thank the Lord) outlived his projected lifespan by a number of years, and who is hanging in there as I write.
First of all, you have to decide what drug to look at. This takes research, even if it is just talking to your oncologist. I relied on a CLL expert to guide me in my choice of clinical trials, up to a point. I must admit that, while I am an expert on my own body and how I feel, the CLL expert has seen hundreds of cases, and is more of an expert on how my disease will, in general, progress.
I thought long and hard about my first trial I undertook in 2006. I researched everything the CLL doc told me were my options (and the field is pretty wide open when you are untreated). Yes, I was drowning in green tea back then, but I was still progressing, so my doc and I agreed that I needed something stronger to knock the CLL back.
I also looked at the trials his institution offered. I asked about each of them. I then searched on the top five or six that seemed as though they might be good for me. I printed out study after study, and, using a highlighter, I marked the response rate, the side effects, the burden of treatment (would I have to stay in the hospital) and so on. I then went to clinicaltrials.gov and looked at everything that seemed familiar, and a few that didn't. I had been tracking and thinking about clinical trials since I had been diagnosed some eight years before, so I wasn't unfamiliar to the terrain.
Next, I needed to make a decision about what phase trial to look into. A refresher: a phase one trial is a dosing safety trial, meaning they ramp up the drug until unacceptable toxicities are found. A phase two trial is an efficacy trial, that is, does the drug show any activity in the disease. The phase three trial compares the new drug with the standard treatment. (Placebos are never used now in lieu of treatment; it is considered unethical to withhold at a minimum the 'gold standard' treatment, though that hasn't always been the case, in the old, bad days.)
The problem with phase one trials is poetically described in another way to look at these trials: First-in-Man trials. (Many drugs have been used elsewhere, but the name tells a lot.) The phase one trial is given over a range. The first patient usually gets a dose that is far too small to do anything at all. The subsequent patients are given higher and higher doses, until bad things start popping up. Pre-clinical trials give a hint of activity in humans, since they use human cells in culture, as well as the ubiquitous mouse and rat studies.
I have undergone a phase one trial, but I try to avoid them for the reasons outlined above. If you press the trial coordinator, he or she will generally tell you what the other patients in the phase one trial have experienced. But that isn't a foolproof guide. In my phase one trial, the trial coordinator told me to expect flu-like symptoms. (This is such a common description of side effects, it's a little like telling a diner that mongoose or arctic wombat 'tastes like chicken'.) To say I had 'flu-like symptoms' was something like saying the Titanic had a little problem with an iceberg.
I puked my guts out! It was horrible. Yes, I experienced projectile vomit! It was even green, something like the Exorcist (I had a huge helping of spinach quiche the night before.) I've never had such a terrible flu, or if I had, I've blocked it from my memory to protect me from insanity. (Because of my, and others, experience, they now give anti-emetics, or drugs to quell nausea. Thanks, guys, what took you so long?
I prefer the phase two trial. Generally, in a phase two trial you are guaranteed to get the drug (not so in the phase three trial, which is, after all, a comparison trial). The maximum tolerated dose has been established. Anti-nausea drugs have been prescribed. Dosing schedules may been worked out, more or less. Results have been published on the experiences of the first trial (yes, my experience is now part of the record...). You have a better idea of the risks and benefits of the trial.
The phase three trial, as I mentioned above, has the huge disadvantage of not giving the investigational drug to all comers. This is very important in a serious and fatal cancer such as CLL. Why, you could get the standard treatment without going through the qualification process, all of the scanning, all of the prep work, and so on. Some trials do try to 'sweeten the pot' by offering the new drug to 2/3 of participants, instead of a 50/50 split. This is much better for the patient, but this isn't a common practice, for some reason. The best option of all is to give the drug to everyone, and compare their results with historical controls. Hardly any researcher likes this option, which is too bad for the patient community.
My next post will deal with the very real barriers to patient's signing up for trials. It seems to me that not enough researchers are concerned with how we feel about the clinical trial process.
Saturday, May 30, 2009
The FDA has taken that lesson to heart. Do nothing is the wisest and safest course. If you approve a drug or device, such as Vioxx or breast implants, and there is even the hint of health problems, you will be hounded by lawyers forever. And the drug companies, which put out largely a safe product, will be tarred by the negative publicity surrounding the drug.
As part of the massive deficit spending by this administration, some money is supposed to trickle into cancer research. As the following editorial points out, the last time money was poured into reaseach, it all 'disappeared into a thousand tiny holes.'
The author of the following piece argues that the FDA has to do better this time. Instead of waiting years and years for drug efficacy to be demonstrated by over-all survival, it needs to accept surrogates for effectiveness, such as progression-free survival (PFS) as good enough to move a drug forward.
The Next Front in the War on Cancer
Faster clinical trials are critical if we are to save more lives.
By MARK THORNTON
On Tuesday, President Barack Obama announced a massive initiative against cancer. "Our recovery plan will launch a new effort to conquer a disease that has touched nearly every American, including me," he said in his speech to the nation, "by seeking a cure for cancer in our time."
Specifically, the president was referring to a provision in his stimulus bill that will direct a tranche of funding to the National Cancer Institute (NCI). The money will come from the $10 billion that's being steered to the National Institutes of Health, and it will, for the next two years, match the surge in spending on cancer that occurred between 1999 and 2003.
But despite the lofty goal set by Mr. Obama, it appears that the NCI is not mapping out a specific plan or strategy on how to most effectively use its new money. It is simply going to pour more money into the cancer research community.
In 1998, a new day was dawning in cancer research. The genomic codes of cancer were being broken, and an explosion of new vulnerabilities was being discovered that had the potential to reveal hundreds of new "drugable" targets. The hope then was that this would quickly produce a cure.
The dream was that this dramatic funding increase would break the back of cancer.
It didn't. Now that the money has disappeared, the diagnosis of cancer is no less fearful in 2009 than it was in 1999.
Read the rest at:
Our lives depend on doing a better job, folks!
Monday, May 25, 2009
This paper in Blood points out the chilling fact that rituximab has been linked to a serious brain disease, progressive multifocal leukoencephalopathy (PML).
Progressive multifocal leukoencephalopathy after rituximab therapy in HIV-negative patients: a report of 57 cases from the Research on Adverse Drug Events and Reports project
Kenneth R. Carson, et al
Rituximab improves outcomes for persons with lymphoproliferative disorders and is increasingly used to treat immune-mediated illnesses. Recent reports describe 2 patients with systemic lupus erythematosus and 1 with rheumatoid arthritis who developed progressive multifocal leukoencephalopathy (PML) after rituximab treatment.
We reviewed PML case descriptions among patients treated with rituximab from the Food and Drug Administration, the manufacturer, physicians, and a literature review from 1997 to 2008.
Overall, 52 patients with lymphoproliferative disorders, 2 patients with systemic lupus erythematosus, 1 patient with rheumatoid arthritis, 1 patient with an idiopathic autoimmune pancytopenia, and 1 patient with immune thrombocytopenia developed PML after treatment with rituximab and other agents. Other treatments included hematopoietic stem cell transplantation (7 patients), purine analogs (26 patients), or alkylating agents (39 patients).
Median time from last rituximab dose to PML diagnosis was 5.5 months. Median time to death after PML diagnosis was 2.0 months. The case-fatality rate was 90%. Awareness is needed of the potential for PML among rituximab-treated persons.
The other great disease which causes immunosuppression of course is AIDS. These patients can be struck by reactivation of the JC virus. It seems less common in CLL patients, at least it is not described in the literature to any great extent.
You don't want to get PML. It is caused by the JC virus, which is present in almost all adults. It lives in the body, harmlessly, for years. In cases of immunosuppression, occasionally it will attack brain tissue, leading to gross mental deficiencies, and in most cases, death. See the wikipedia article on the JC virus:
It should be noted that since all CLL patients are immunosuppressed, the disease may strike with or without rituximab. However, those using rituximab seem to be at a higher risk of developing the disease. Cases of PML were probably 'hidden' in the general population of immune-deficient patients such as those with CLL, so it was not clear and evident. In those with other diseases who are not immunocompromised, these cases are so atypical as to be suggested to be caused by the rituximab.
He has posted an interesting protocol on his blog, http://dr-savostianov.blogspot.com/2008/08/chronic-lymphocytic-leukemia-treatment.html
I confess that I find his English to be of the sort of "Borat: Cultural Learnings of America for Make Benefit Glorious Nation of Kazakhstan". However, one needs to accept the premise that his therapy for CLL is interesting and worth a second look, primarily because it is cheap and, if verified, provides a vastly superior complete remission rate than most therapies, with the exception of FCR.
He apparently begins his therapy with prednisone and radiation to the tonsils, spleen, abdominal lymph nodes, and liver. He then administers chlorambucil. He believes that knocking back the pool of CLL with the prednisone and radiation permit the chlorambucil to deal a heavy blow to the CLL. He warns, however, that any departure from his schedule will leave the patient with a case of drug-resistant CLL.
He says this technique is free of immunosupression, and if it does occur, it is a simple matter to remediate.
Make up your own mind, but there is enough sense in this that perhaps there is some merit to it. Certainly it does not depend on expensive drugs such as rituximab, fludarabine, and Campath.
Friday, May 22, 2009
The following article is important for two reasons. First, it lets the companies advertise rituximab for use in CLL. There are competitors coming, namely Arzerra (HuMax-CD20), which should be approved for CLL this year, as well as several other CD20 drugs.
Secondly, with Obamacare looming, it is likely that off-label drug usage will be curtailed if not eliminated totally. With CLL such an important revenue source for the drug companies, it would behoove the company to have as many applications as possible for the drug already in place.
Here's the press release:
Genentech And Biogen Idec Submit Applications To The FDA For Rituxan For Most Common
Article Date: 22 May 2009 - 4:00 PDT
Genentech, Inc. and Biogen Idec (Nasdaq:BIIB) announced that the companies submitted two supplemental Biologics License Applications (sBLAs) to the U.S. Food and Drug Administration (FDA) for Rituxan® (rituximab) plus standard chemotherapy for people with previously untreated or treated chronic lymphocytic leukemia (CLL). The companies will request a priority review, and if granted, anticipate the FDA will make a decision within six months.
The applications are based on positive results from two of the largest global Phase III clinical trials conducted in patients with CLL. The randomized, comparative studies, known as CLL8 and REACH, showed that Rituxan plus standard chemotherapy for CLL extended the time patients lived without the cancer advancing (progression-free survival or PFS) compared to those receiving chemotherapy alone. In CLL8, previously untreated patients who received Rituxan plus chemotherapy had a 69 percent improvement in PFS (41 percent risk reduction, hazard ratio=0.59; p<0.0001; 95% confidence interval: 0.44,0.72) compared to those who received chemotherapy alone.
Wednesday, May 13, 2009
For some dumb reason, I thought the only people who would read CLL group messages would be other patients. To be honest, I thought that oncologists and nurses were way too busy to even think about searching on the terms of a trial to see what patients in that trial were saying.
I've known for a long time that financial creeps troll the patient groups, looking for any information they can use to make financial decisions. Although less than honorable, I guess it's something that wouldn't surprise me too much.
But to have my health care practitioner looking for posts on a clinical trial floored me.
I am much more careful now. If I have anything at all even remotely critical to say, I say something like, 'a famous CLL doctor', or a nurse at one of the top CLL centers.' I'll use it every time I didn't want a particular doctor to read what I said about him.
After all, there is no reason at all to get your doctor or nurse mad at you.
The web is a huge party line. (Older folks are at least a bit familiar with the concept of the telephone party line. We used to have one. It was cool, but inconvenient at times.) Be careful what you say!!!
Tuesday, May 12, 2009
Hmmm. Easier to experiment with this than cancer vaccines or ofatumumab (Humax-20). Since I don't have a lab with a newly-minted PhD., I am restricted to trying out substances that are easily available. There are a few out there, and that's why I keep perusing the medical literature, looking for any little angle that might help slow the runaway train that is my CLL.
Well, I alternated the two drugs, changing them every 24 hours. I didn't 'wash' my cells, but I did remain hydrated, which doesn't wash cells but is important to all of us, anyway.
The results have been less than spectacular. My counts are pretty low after my four cycles of FCR, ending early because of persistent neutropenia. (The famous doctor at MD Anderson who said he could give me three years with FCR was off by about 2.8 years...)
My main gauge of success/failure of any treatment is, number one, the WBC count, and two, the size of my massive abdominal nodes. Since my counts are fairly low, I really only have my abdominal node size to go by. I sort of can tell whether things are shrinking or not by how tight my pants are.
I used to be a not-very-svelte 36 inch waist size (there was a time when a 32 waist was loose on me; I think that was the Nixon administration though). After I developed the 11q deletion after my HDMP+Rituximab (high dose steroids with high dose rituximab), my waistline started to morph out of control. After the 36 inch pants became too tight, I opted for the 38, then the 40, and then the 42. So in one year, I gained six inches in waist size without gaining an ounce of over-all weight.
Sad to say, even after about three weeks of the EGCG-curcumin-EGCG shuffle, my pants weren't a bit looser. So, I deem the effort a failure.
However, I did feel pretty good during the time, no night sweats, no hot flashes, no increase in fatigue, and my counts didn't suffer.
Why didn't I see better results? Two reasons, I think. First, I have very advanced, stage IV CLL. I've been fighting poor-prognosis CLL for over 10 years now, and I've developed, I'm sure, lots of bad chromosomal changes and increase chemo-resistance.
The second reason, probably much less important, but important nevertheless, is the abysmal bioavailability of both EGCG and curcumin. It's one thing to dump a teaspoon of pretty curcumin in a witch's brew of CLL cells; it's another to achieve an equivalent level of curcumin in one's bloodstream.
The usual trick is to take curcumin with bioperine. One must be careful not to overdo this compound. Too much apparently isn't good for you. The other thing is to dissolve the yellow, highly-stainable curcumin into warm or hot coconut milk. The high fat content of the coconut milk definitely does dissolve this spice. I also add a little bit of alcohol to help dissolve the product, usually amaretto. The latter adds a nice flavor to the concoction. Margaret swears by the C3 complex that comes from Sabinsa corporation. A number of companies use that product to make their offerings that are available retail.
The EGCG I usually use is Teavigo. This is available from a variety of suppliers; I purchase mine from The Vitamin Shoppe, which has a reasonable price for the product, and sometimes offers free shipping for a certain dollar amount of purchased product. I add another EGCG extract with a different formulation just to cover all my bases.
Both are supposedly best taken on an empty stomach. I will tell you that the EGCG is very rough on my stomach, so I do eat something perhaps fifteen minutes after swallowing the pills. It will make me throw up if I wait any longer.
My 'guru' on curcumin is Margaret, who posts on her own Multiple Myeloma blog. She's an older hand at the curcumin business, and has really benefited by using the spice. Her blog, 'Margaret's Corner', is one of the blogs listed on the right side of this blog post. She is a wealth of information on curcumin, including a section on how to get rid of curcumin stains, which I will attest gives anything you touch after you've pulled apart the capsules a very bright, vivid yellow, which will not wash out.
I was taking to wearing an old, ratty robe while making the curcumin mess. My wife gave this robe a pretty pink color after washing the formally white terry cloth with some red shirts. Now this pink robe has several splotches of screamingly yellow curcumin stains on it, that defy all attempts to remove them.
I suppose my entire digestive tract from top to bottom is now fluorescent yellow in color. I wonder if that would show up on an MRI?
The track record of NICE when it comes to cancer drugs is poor. UK residents just don't have the panoply of therapies available in other countries, including the United States.
Everyone is in favor of cost-effectiveness, right? Well, if you are, remember that CLL patients are a very small lobbying group, and drugs such as Rituxan and Campath are very expensive.
If you are concerned about the treatments you will be getting in the future, pay very close attention to the details. It's one thing to say you are going to cut health care costs; it's another when the savings comes from denying care to you.
I'm reserving judgment until more is known about the president's plan. I will be seeing if health care will be changed for the worse.
(In my opinion, the best thing would be to increase spending and make a serious move to start curing cancers. Imagine how much more money cancer patients would be saving the health care system, and paying into the entire economy, if they could be free from the illness and pain of cancer!)
Sunday, May 10, 2009
He was visiting the renowned cancer facility in order to undergo treatments for his own cancer, chronic lymphocytic leukemia (CLL). Although originally believing the cancer-killing properties of radio waves would be limited to solid tumors, Mr. Kanzius couldn't help but wonder if it could help cure his own cancer. Unfortunately, he passed away in February, 2009, as preliminary testing of his invention was underway. He always knew that it was a long-shot, but he reserved hope that he might benefit from the machine he created.
Meanwhile, research on the Kanzius invention continues. Doctors at MD Anderson, who were initially intrigued by the possibilities of marrying radio waves and nanoparticles, have made progress. The latest news released on May 8, 2009, demonstrates that the Kanzius machine can indeed kill CLL cells.
Reported by David Bruce and published on GoErie.com, the external radiofrequency generator can kill CLL cells while not significantly damaging normal cells, an important finding.
This finding was ascertained in December, 2008, using the cancerous cells of 19 CLL patients. However, the results are only a tantalizing hint at the possibilities of the machine. Dr. Steven Curly of MD Anderson, who has been spearheading the research effort, said that the CLL killing was probably due to the heating of the cells, which are tagged with gold nanoparticles, attached to a monoclonal antibody that attaches to CLL cells.
So, another step forward. According to the article, the percentage of CLL cells killed was not enumerated, so I can't tell how effective the treatment was, nor can I tell from the article how long the duration of the RF field exposure was, what antibody was used (I'm assuming a rituximab-like MoAB), or any other parameter that would be vital to know.
I've read elsewhere that theis RF generator can heat cells up to 600 degrees or so, plenty warm to kill them. Of course, non-CLL B lymphocytes express the CD20 marker, so it would seem that the machine could potentially kill every cell that carried sufficient gold nanoparticles.
Ideally, this would work as a 'super-rituximab' that, as long as a cell expressed the CD20 marker in sufficient quantities, it could be killed by the machine.
For the full news article, go to http://www.goerie.com/apps/pbcs.dll/article?AID=/20090508/NEWS02/305089932/-1/NEWS02
For more information about the Kanzius Cancer Machine, go to http://www.kanziuscancerresearch.com/
Friday, May 1, 2009
Believing that reducing cholesterol in my diet and reducing it further by adding a bit of fiber to my diet probably won't hurt me, I embarked about a month ago on a fiber-added diet. I must report that the results of my little experiment is inconclusive at best.
One of the 'problems' is that, at the present time, my WBC is quite low, below even the normal range due to my recent bad experience with FCR (fludarabine, cyclophosphamide, and rituximab) for my CLL. So I can't report a huge drop in the WBC numbers. I can look at the ratio of neutrophils to lymphocytes (the two largest components of the white blood count). It has bounced around, but still shows too many lymphocytes. The ratio has not changed for the better.
So, I am not bouyed by these results. I will continue to add a teaspoon a day to my diet, because I probably don't get enough fiber as it is, and adding a bit won't hurt. Didn't seem to help, don't think will hurt.
I'm thinking on embarking on a different CLL journey in the near future; alternating EGCG with curcumin. A recent paper shows that the combination seems to work better than either does alone.
Wednesday, April 29, 2009
Tuesday, April 28, 2009, 2:34pm EDT
Following patient death, Cephalon warns of using Treanda with allopurinol
Philadelphia Business Journal - by John George Staff Writer
Cephalon is updating the prescribing information for its cancer treatment drug Treanda to include a warning about the use of the drug with allopurinol, according to documents filed with the Securities and Exchange Commission on Tuesday.
According to the filing, the Frazer, Pa., biopharmaceutical company identified two cases of Stevens Johnson syndrome in patients treated with Treanda and allopurinol — one of which was fatal.
Allopurinol is used to decrease levels of uric acid in certain cancer patients.
Stevens Johnson syndrome is a rare, and potentially deadly, skin disease.
Treanda was approved last year by the Food and Drug Administration as a treatment for chronic lymphocytic leukemia and non-Hodgkin's lymphoma.
“Although the relationship between Treanda and Stevens Johnson Syndrome cannot be determined, there may be an increased risk of severe skin toxicity when Treanda and allopurinol are administered concomitantly,” Cephalon (NASDAQ: CEPH) stated in its filing, adding that allopurinal is known to cause the syndrome.
The updated prescribing information is expected to be implemented in early May, the company said.
Tuesday, April 28, 2009
As a barometer, Google News has bumped the story from the headlines, from the sidebar, to related stories below the fold, so to speak.
I think everyone is mystified, but thankful, that the flu so far is very, very mild, except in the country in which it started.
Sunday, April 26, 2009
Over 100 people are now dead in Mexico, the apparent epicenter of the flu. No one has reportedly died in the United States, and many of the victims appear to be in their teenage years. The disease has been characterized as 'mild' in the US, with all victims apparently on the mend, or at least not getting seriously ill. Whether that continues remains to be seen. It is possible that the Mexican flu has gotten a foothold in that country, and authorities have been slow to respond, while in the US with its superb medical system, doctors have been treating appropriately, and early. The general better health of Americans may also play a part, in my opinion. The disease has seemingly been appearing (so far) only in people who have recently returned from Mexico. These people are wealthy enough to travel, and probably in good health, since sick people generally don't wish to travel.
Chronically ill people in the United States need to be hypervigilant. This means avoiding crowds, staying away from coughing and/or sneezing people, and washing their hands frequently. I personally would suggest considering not going to work tomorrow and in the next few days or weeks, especially if the Mexican flu has been detected in your city. I also suggest avoiding or limiting contact with children or teenagers in school, since that is a perfect environment in which to foster the spread of this serious disease.
I still work, and live in Sacramento California where a possible case was just discovered in a student who recently came back from a trip to Mexico. His school has been closed as a precaution. I may still go into work, since I have an office with a door that can close. I purchased a wall-mounted germ sterilizer, which I hope will help kill any viruses that sneak in under the door. If the flu seems to be spreading in Sacramento, then I will stay home. I also will discuss with my supervisor my need for precaution, and explore the possibility of working from home, something my employer has refused vehemently to date. I do have plenty of sick leave and vacation, which I will not hesitate to use.
As the old television program advised, "People, let's be safe out there".
Saturday, April 25, 2009
As I write this, Mexican Flu cases have appeared in California, Texas, Kansas, and New York. So far, no deaths linked to the flu have been reported. It will likely not be long before we learn of the first death of an American to the Mexican Flu.
For CLL patients, and others with serious, life-threatening conditions, this comes as frightening news. The Mexican Flu is eerily similar to the Spanish Flu pandemic of 1918, killing healthy young adults (20-40) rather than the usual children and elderly populations.
The specter of bioterrorism has already been raised, but it doesn't take a terrorist attack to bring the potential of such a calamity to our world, already battered by a severe economic downturn. You'd think someone had it in for us. Maybe they do.
The misery of the Great Depression was worsened by a long drought resulting in the Dust Bowl. We now have a potential pandemic in the midst of another serious money panic. Do these things go together.
The President of Mexico has now exercised emergency powers. This comes as Mexico failed to respond with the first inklings that something out of the ordinary was going on. Only when the First World (The US and Canada) were able to analyze the genetics of the victims in Mexico did everyone realize there was a flu that seems to meet all of the requirements of a pandemic: human-to-human transmission, humans can become infected with it, and the populace has no immunity to it. In my opinion, these conditions have already been met.
I will be interested to see what happens to the stock markets of the world on Monday. If the news continues to get worse, a nascent recovery will die a quick and early death.
The government claims they are ready to stem a pandemic quickly. We'll see how this pans out.
Meanwhile, keep doing what you should have been doing all along; wash your hands frequently, avoid crowds, avoid sick people, cover your nose and mouth while sneezing or coughing.
Sunday, April 19, 2009
Here's a news blurb on the subject if you want to read a bit more on it. The technique may protect healthy cells more than kill cancerous ones.
The article quotes a researcher at the University of California, San Diego who cautions that not enough is known in the human population to predict if this technique would be effective. There are some cancers, he notes, that some cancers have already altered metabolic functions in normal tissue already, and fasting might not add anything to the current treatment regime.
Interesting to note, though. I wonder if any CLL researchers have an opinion on this now, or if they will take refuge in the all-purpose answer, "it's too soon to know yet."
Tuesday, April 14, 2009
I have somewhat of a complicated return, so I've in my third week of working to get this monster done. It's nip and tuck whether I can finish on time.
On the other hand, I've never failed to get at least the federal return in on time. I hope I stay healthy enough for one more day...
Sunday, April 12, 2009
Me? I'm so addicted to food that when I fast, all I think about is food. I could fast one day. Two days? I've had to do it before a colonoscopy that I had late in the day one time. All I could think about was food.
I think it would be worth a try!
I'm through with FCR, so this advice comes a bit late for me.
When it's your life, this might be something to at least run by your onc doc.
Tuesday, April 7, 2009
Once my heart stops beating, the CLL cells are going to soon be feeling the pinch. Nutrients are going to stop coming along, the blood flow bringing oxygen and taking away carbon dioxide simply won't be there. The protective vitamins such as vitamin C the cancer cells use to fend off death are going to be used up, and no longer serving a purpose. The CLL cells begin to die.
Obviously, this is a drastic (but 100% effective) CLL cure. Can we use this impractical information to our advantage? I think so.
We can perhaps slow the growth of the CLL clone by denying them the stuff of life. With our limited knowledge (we don't know, for example, what drives the CLL cells to merrily proliferate until it kills us, and it), we can't cure CLL by 'gentle means', but perhaps we can slow its growth.
And since CLL is an indolent (slow growing) cancer, with a potential lifespan of more than a few years, slowing the growth may mean months or even years more of good quality of life. This means, perhaps, more of us will be around when truly effective treatments are finally available.
I'm going to discuss one of those vital constituents as I see them, that the CLL cells require to madly and indiscriminately split and split and split. That's cholesterol.
Several papers have been published that point out that the standard cholesterol tests are not a valid indication of the cardiovascular health of the CLL patient (http://tinyurl.com/dha4hc). It seems that both high-density lipoprotein, HDL (the 'good' cholesterol) and low-density lipoprotein (LDL, the 'bad' cholesterol) is decreased in the CLL patient as the disease progresses.
Consider this paper in PubMed: http://tinyurl.com/dmegog. It asserts that cholesterol levels are reduced in progressive blood cancers including CLL, and that cholesterol levels rise when there is a response to chemotherpeutic intervention.
It's tempting, then, to conclude that the rapidly proliferating CLL cells 'sop up' large amounts of cholesterol to support their indiscriminate breeding. It may follow, then, that limiting the amount of cholesterol available for these cells to grow might slow the proliferation down.
I'm not aware of any studies that have tested this idea in CLL, but the idea has been floating around for some time. It's been known for years that high cholesterol is a risk factor in the development of cancers, but as far as lowering the levels as a means of slowing cancer's growth, much less is known.
There is one interesting paper, though, that concludes that the use of one type of statin drug (which is designed to reduce cholesterol levels), simvastatin, seemed to cause a slowing of the growth of the clone (http://tinyurl.com/cbzaac). Ironically, it was noted in the paper that some 40% of this very small sample of patients, went on to require treatment the following year. It is unclear from the abstract whether these four patients were the same ones who had noticable effects on their CLL clones. The apparent conclusion these researchers reached was that the use of statins may actually increase the need for treatment. The very small sample size makes reaching that conclusion difficult.
It seems reasonable to consider moderating the amount of cholesterol coming through the diet. The body is perfectly capable of manufacturing enough of the substance to meet the needs of the brain and body without necessarily consuming it.
This means going on a low cholesterol diet, exactly the same as one would adopt if one was concerned about heart disease. Low saturated fats, avoiding all sources of cholesterol in the diet, lean proteins, use of good fats in lieu of 'bad' fats, and so on. There are plenty of these diets and advice elsewhere on the web.
Another way of lowering cholesterol is to eat a higher-fiber diet. This includes both soluble and insoluble fiber. By increasing the bulk of the stool, the amount of bile acids excreated is increased. And since we know that these substances contain cholesterol, this effort can decrease cholesterol further.
We can't go too far, because a certain amount of cholesterol is necessary in the body, so I'd talk it over with your doc, and track your over-all cholesterol level.
Maybe it would have a slight, but real, effect.
Saturday, April 4, 2009
I don't have results. Dr. Kipps has held off with any thoughts of other treatment until we get the results. I would have thought I would have heard about the results by now; perhaps he just doesn't want to give bad news?
I've had somewhat of a hard time dealing with my failure on FCR. My blood numbers are OK, a little low, but OK. However, the percentage of the white blood count that are lymphocytes are going up, and the percentage that are neutrophils are going down, obviously a poor sign.
He mentioned getting a Neulasta shot on Wednesday, but I forgot about it and the physician's assistant also apparently forgot about it. I have a call into Sheila Hoff, but have not heard back from her. I would I guess (now) get the shot in Sacramento, since it would be ludicrous to fly back down there for a shot.
I wish I had remembered, not that they shouldn't have arranged it themselves. Failure all around.
Sunday, March 22, 2009
We have our dog in the vet, recovering from a splenectomy (yes dogs get them as well).
There was a beautiful, young, chocolate-colored dog in another pen. He was restless when I first walked by him, but despite being on anti-seizure medicine, he was getting more and more restless. As I was visiting my dog, and could more clearly see him, I noticed he was basically having full, constant, convulsions. His eyes were staring straight ahead, and his limbs where flailing around as if his whole body was in relentless, terrible motion. It was one of the most horrific things I've had to witness.
I overheard the vet techs talking that they had given the maximum dose of the anti-convulsive drug that they could. He was getting worse and worse, they said. The dog could not swallow even a drop of water.
I asked the vet tech standing nearby what had happened. She said that the dog had eaten snail bait.
I've since found out that snail bait contains metaldehyde, a toxin that is poisonous to animals, wildlife, and children(!). It is flavored with molassas to be attractive to snails. You can imagine what a young puppy would do when there was tasty 'meals' spread around the back yard.
Why this product is permitted to be sold is beyond me. Obviously, the poor dog's owners cared about their animal, because they took him to the emergency vet. Yet they apparently didn't read the small warning label on the back that warned against putting the product where dogs and small children could find and eat it (yes, children have died from eating this crap).
There are other snail control products available that don't contain metaldehyde. And there are of course other control methods that don't subject animals to a slow, painful death.
Seeing that poor animal suffer such a heart-breaking event was enough to be seared in my mind as long as I live. If others could see that dog, I wouldn't believe that metaldehyde wouldn't be banned immediately for at least residential use.
PLEASE PLEASE PLEASE don't use this product where pets, wild animals, and even children could encounter it. This is not a painless death. It is torturing an animal to death.
Thursday, March 19, 2009
I still have low platelets, low WBC, am neutropenic, but as of the results of the last blood test I've seen shows, the hemaglobin has come back and is now in the 12.5 range, which is a lot better than the 7.9 range I was in last fall.
I see Dr. Kipps later this month. I'll have a BMB and get his usual thorough exam. I know I have not had a molecular remission, nor a complete remission, since I still have enlarged nodes. We will see what kind of partial remission I'm in.
One unfortunate note is that we are dealing with a sick dog. He has been diagnosed with hemangiosarcoma, which is a cancer of the blood vessel cells. He has a massive spleen that could rupture with fatal results at any time. We've been offered surgery with the hope he may live another few months, but since he is 16, has an undetermined secondary mass in his stomach, we probably won't put our old guy through that.
Spring has come early again to Sacramento, with the fruit trees blossoming with all vigor.
Saturday, March 7, 2009
Niacinamide is a form of vitamin B3, and is generally found to be safe even in relatively high doses. Caution is called for, though. It's a good idea to check with the doc regarding the use of this or any other supplement. Also, the increase in counts is temporary (darn!). It may help us be safer from infections, though.
I hope there are more studies in this area. Neutropenia is a serious problem that (obviously) can kill.
The doses cited in the paper work out to between 750-1500 mg for a 165 pound man. The RDA is only 16 mg, so this qualifies as more medicine than supplementation. Also, niacin, the other common form of vitamin B3, has been linked to the growth of new blood vessels in the tumor. Tumors can't grow past a certain point without vascular support. This is true even in CLL, since lymph nodes need new blood vessels to grow, and increase microvascularization in the marrow has been linke to CLL progression.
Vitamin B3 Fuels Neutrophil Production 2/23/2009
As the first line of defense against invading microbes, neutrophils
are the “foot soldiers” of the innate immune system. Upon release
from the bone marrow, neutrophils circulate in the blood for only a
few hours before homing to peripheral tissues where they survive at
most for 2 or 3 days. To keep up with the heavy demand for these
short-lived cells, a normal healthy adult produces approximately 10 to the 11th power
neutrophils each day and up to 10 times that number in the setting of
Cancer patients undergoing chemotherapy often experience disruptions
in neutrophil homeostasis, which places them at increased risk for
infection. The ability to boost neutrophil production with
recombinant granulocyte colony stimulating factor (G-CSF) has
revolutionized care for patients with chemotherapy-induced febrile (fever)
neutropenia. However, the molecular mechanism by which G-CSF induces
myeloid differentiation remains poorly understood.
A team of researchers at Hannover Medical School in Germany recently
reported a major breakthrough in neutrophil development that may have
important clinical implications. Upon binding to its receptor on the
surface of myeloid progenitor cells, G-CSF turns on an enzyme that
converts intracellular vitamin B3 (nicotinamide) into an activate
metabolite (nicotinamide monocleotide). The researchers found that
this is the rate-limiting step in a signal transduction pathway that
Addition of vitamin B3 or its precursor induced granulocyte
differentiation of cultured hematopoietic stem cells. Administration
of high doses (10-20mg/kg/day) of vitamin B3 to six healthy
individuals resulted in significant increases in neutrophil count over
a 7 day period and a return to physiological cell counts when vitamin
B3 was withdrawn.
These findings identify a new role for vitamin B3 in granulopoiesis
and beg for clinical trials to evaluate the use of vitamin B3 either
alone or in combination with G-CSF for the treatment of neutropenia.
Skokowa J, Lan D, Thakur BK, et al. NAMPT is essential for the
G-CSF-induced myeloid differentiation via a NAD+-sirtuin-1-dependent
pathway. Nat Med. 2009;15(2):151-158.
Thursday, February 26, 2009
She said she would schedule an MRI to check the abdomen. However, I know the nodes never were significantly reduced by the FCR, though I did have a response even there. Just not enough.
My response in the blood/marrow was good, I guess, though I have been mired in neutropenia land for almost two months.
Knock on wood and prayers...I have not been sick with an infection, though every tiny cut gets infected and it takes forever to resolve them. I have been dealing with gastric problems for years, and that has not improved either.
I also with have a bone marrow biopsy next month with Kipps. I will see how terrible my marrow is.
After a nice eight-year really non-eventful life with intermediate risk CLL, my cancer has not been kind to me at all.
On the positive side, the number of trials for CLL continues to increase, and there are a number of theories out there that sound really promising. I just don't know if I'll be around to get to try any of them...