Experimental therapies are therapies which have not been thoroughly tested yet, and consequently approved by the FDA in the U.S. and other similar bodies in other countries. Experimental therapies can be obtained in the following ways:
1) by entering a clinical trial sponsored by a cancer research center, or by a private company
2) by finding an oncologist willing to administer agents used in an ongoing clinical trial according to the directions of research originators, provided that the agents used have been approved or can be obtained via "compassionate use"
3) by identifying an agent tested and used abroad but not yet available in your country, and then finding an oncologist willing to obtain it and administer it
4) by finding an oncology practice which is doing its own clinical research, and has developed an innovative protocol
CLINICAL TRIALS
Clinical trials come in three varieties. Phase I tests dosage amounts and toxicity,
and is usually open only to patients with advanced disease. Phase II tests
effectiveness, and phase III compares the new treatment with older established
treatments. Unfortunately, there is no one place to get comprehensive information
on clinical trials. The place to begin is by calling 1-800-4CANCER; they list all
trials sponsored by NCI. Then contact the LRFA or CFL for the insider scoop. The
CancerGuide has several helpful pages on trials:
www.cancerguide.org/clinical_trials.html
www.cancerguide.org/internet_trials.html
www.cancerguide.org/trials_glossary.html
Information on foreign trials is even more difficult to obtain. Hiring a medical
researcher is probably the best way to go. How to do this:
www.cancerguide.org/search_service.html
TRIAL EMULATION & FOREIGN TREATMENTS
If you cannot or will not enter a trial, or if you have identified a promising foreign treatment, you can discuss this with your oncologist and find out if he or she will be willing to investigate, obtain, and administer it. Many cancer patients have done so. One such successful story is described in Beverly Zacharian’s book Activist Cancer Patient. It is a good idea to gather some information first which you can then offer to your doctor for study and further discussion.
INNOVATIVE CLINICAL PRACTICE
Clinicians that also do their own research are rare in the U.S. but more common in Europe. Nevertheless, innovative oncologists can be found; Dr Block in Evanston, IL is one such specialist. Such clinics care about gathering good data, and publish their results. Sometimes they run small clinical trials. And some alternative clinics have begun to do their own research as well.
Participating in a trial can be risky -- the treatment may look good so far but be shown later to be no more, or even less, effective than what is currently available. On the other hand, most current treatments for lymphoma leave much to be desired, and it can well make a lot of sense to try something new. If you do try something new, please tell others about your experience -- the side effects, the efficacy, and anything else you care to share. You can post it online, or communicate it to the LRFA or CFL.
Emulating a successful foreign treatment that has already undergone rigorous trials in Europe, Japan, or elsewhere, is less risky, and can make a major difference. U.S. oncologists in particular are slow in adopting successful foreign practices, partly because the FDA requires retesting for approval in the U.S., and partly because -- forgive my bluntness -- Americans think they are the world, and whatever worth having is already available here. :-)
Sometimes, agents available abroad are not available in the U.S. AIDS activists won a special dispensation for AIDS patients, so that they could order unusual substances from abroad. Perhaps with the recent FDA reforms, the same policy now applies to us as well. In any case, your oncologist can find out the status of an agent and its availability.
One way to identify potential agents you may be interested in is to check the archives of the nhl-low list. Ben Haines, the list owner, has been compiling two files. One is called "promising protocols," and lists all known protocols for low-grade lymphoma (largely overlapping with agents suitable to the higher grades). The other list is "antiangiogenesis therapies" which lists all the various anti-angiogenesis agents that are currently in early trials or under development. Ben updates these files monthly. (You may also want to check out another regularly posted file called "cancer breakthroughs.")
What follows is an account of the experience of one person with follicular lymphoma who recently enrolled in the IDEC yttrium-labeled monoclonal antibodies trial. Written and copyrighted by Paul Klein, 1998.
Rituxan/Yttrium Trial
Date: 98-07-23
To all who are considering the Rituxan/Yttrium protocol:-
Now that I have completed the full course of the labeled ("hot") Rituxan/Yttrium Clinical Trial, Phase III, let me give you a rundown of the sequence of events in this trial.
My oncologist who heads up lymphoma treatment at Shands Hospital, Gainesville, Florida has been PI (Principal Investigator) for a number of trials in the past. He had headed up the Fludarabine/Interferon trials, among others. He started extolling the virtues of Rituxan about a year ago, talking to my wife and me about it as an option, should I find myself once again in the option-selecting mode. At that time, I had just completed my CVP regimen and was in the w&w (wait&watch) mode. Actually, it was the w&w&w&w&w&w&w (wait&watch&worry&wish&wonder&want&wrestle) mode. When Rituxan+Yttrium came on scene, we talked about that as an option for me. He thought I would be the ideal candidate for that protocol. (Being the "ideal candidate" for some form of cancer treatment was never a childhood fantasy of mine but whattaheck, you take what you get.)
Here's what followed: 5/19/98 Took my routine ultrasound which showed that my largest node which on 1/19/98 had been an unexciting but comfortable 1.9cm in size had now increased three-fold in just 4 months to 5.7cm. That made me think unhappy thoughts: (1) it was located on the vena cava where it threatened the functioning of my kidney, (2) that was a lot of growth in just 4 months; could it indicate transformation to a more aggressive form of NHL? (3) would such transformation exclude me from promising protocols as Rituxan and Bexxar?
5/22/98 Met with my oncodoc where we discussed my options. Incidentally, whenever I visit with my doctor, I come armed with many of the more promising, relevant reports that I have copied from this list. We discuss them. I very often e-mail him items that I find here that I feel would affect my treatment or any other that he might be involved in for other patients. Thanks to this board and the generous contribution of many on it, I had a lot of info about the experience that others have had with Rituxan. So my visits to my doc have become discussions rather than merely examination-and-diagnosis. Incidentally, my wife is also an active participant in these discussions.
My doc had become PI for the randomized Rituxan Trial, Phase III at Shands. We talked about that at great length. Enrollees would be chosen, like the toss of a coin (but by computer, of course), for either the "cold" or unlabeled arm (Rituxan for 4 weekly infusions) or for the "hot" or labeled arm (Rituxan + Yttrium, a radioisotope, over a 2-week period). Each participant's protocol would not become known until two days before treatment was scheduled to begin.
6/22/98 Echocardiogram. This is not required as part of the Rituxan protocol. But since I had had a heart attack (silent) some 9 years ago and had had triple bypass surgery 7 months ago, it was considered necessary. (Rituxan can cause arrhythmias and angina pains in those who had experienced these in the past.)
7/1/98 Office visit with my doctor. Everything looked good. Purely as routine, we decided to look at the results of the echocardiogram. The Ejection Fraction is an important bottom-line measurement of the heart's efficiency. Normal is about 70%. Mine, since my MI, had always run in the 35%-55% range. We summoned up the echo report on the computer and all 4 of us were nearly knocked off our feet. The EF registered 15-20%! Not good; pretty close to heart failure, in fact. None of us could believe the results. My doc scheduled me for a MUGA (Multi-Gathering something or other) which is an objective test for heart efficiency whereas the echo is highly subjective and prone to errors. The MUGA came back with my usual EF of 35%. So we had passed that hurdle -- but not until I had aged about 6 years. (Note: the echo and the MUGA are not required for every entrant. I was just lucky, I guess.)
7/6/98 Had a full-body CT scan, required for the protocol. I'm not terribly keen on radiation exposure, having had far more than my share during my lifetime, before, during, and since my time in the service. So I tried to get them to accept ultrasound instead but I struck out on that endeavor. I was also to get a lymph node biopsy immediately following the CT but a scheduling muckup made that impossible.
7/8/98 Now for the requisite lymph node biopsy and another bit of luck for me. Since my largest node was that 5.7cm mother near my kidney, that was the one of choice. Of course, it also happened to be in one of the most inaccessible parts of my body. But that didn't seem to bother any of the docs; they all seemed very sanguine about the whole thing, especially since it was *my* body that was going to be assaulted -- not *theirs*. They then did a CT-guided needle biopsy, using a needle that was, I would estimate, at least 8 yards long and about a foot in diameter. While in the post-biopsy Recovery Room, I had the required EKG and a blood test.
7/9/98 Bone marrow biopsy. Also required. Inasmuch as I had never undergone one of these I was just a bit apprehensive about it. (If you can call inability to sleep, frequent attacks of stuttering, and walking into walls "a bit apprehensive".) I had heard pretty negative things about it and it just sounds frightening to me. Anyhow, it was nothing much. The Bone Marrow Biopsyer made it almost pleasant. She has a great singing voice and she sang to me during the whole procedure. It hurt (the biopsy, not the singing) for just a few seconds and the whole thing was over very quickly. The two puncture points were sore for a few days; in fact they still are almost 2 weeks later.
7/10/98 (Friday) Got the results of both biopsies -- and it was all good news! The node biopsy showed my original diagnosis: Small cell, follicular NHL, low-grade, no large cells visible. No transformation. The bone marrow showed minimal involvement (<1%). The CT scan showed enlarged tumors in my left axillary (I used to know that simply as "armpit" in those happy pre-DX days) and in my abdomen area. That was good, too. My largest node (the 5.7cm baby), as shown on the ultrasound, showed 2.1x3.7 on the CT. But that was a slice through the tumor that showed height and width, whereas the US showed the craniocaudal (lengthwise, and why couldn't they have called it that in the first place?) view. Good to bear that in mind. Randomization was done and showed that I was to start on the "hot", labeled arm (Rituxan+Yttrium) on Tuesday, 7/14/98.
7/14/98 Wifey and I got to the hospital at 6:45AM. Had the usual blood tests, was given 2 Tylenols and then infusion was started. Along with the infusion, a goodly squirt of Benadryl was injected into the IV so I started talking gibberish very soon thereafter and slept through much of the process. (We had brought along video and audio tapes to help the time pass but we never got to use any of those.) The infusion took about 3 hours. I was then wheel-chaired down to the Nuclear Medicine Department where I was given a syringeful of Indium (takes 3-5 minutes). This is a tracer isotope, emitting gamma rays, that can be followed and analyzed for determining the distribution of the cells that would later be targeted by the Yttrium which emits killer beta rays.
I then underwent an imaging scan that takes a full-body picture, showing where the Indium has congregated. It determines whether it would be safe to give the patient the Yttrium as the second half of the protocol. I had to either stick around for 4-6 hours to take a second imaging study or go home and come back for it. I did the latter, feeling well enough to make the trip back alone. These imaging studies (dosimetry) require that the patient remain absolutely rigid for 30-40 minutes. Otherwise, it's no problem. There is no additional radiation emitted by the scanner. It's all there inside your body, merrily emitting away. The Indium has a half-life of 68 hours. It is recommended that you keep your distance from your spouse, not sleeping (or anything) in the same bed, for 6 days. However, even at the end of 6 days, the danger from the rays is reduced to only 25% of its original. Pretty much the same admonitions for the Yttrium which was to follow.
7/15, 7/17, 7/20/98 Follow-up blood tests and imaging. Ordinarily, one would know at some point in this time frame whether or not s/he was a "go" and that it was safe to get the Yttrium infusion. Not me. With the second infusion scheduled for 7/21, I still didn't know on the evening before whether or not I would be dropped from the study. It seems that there were some problems involving my spleen (I hadn't even known I owned one of those!) and with my bone marrow. In both these cases, the Indium tracing had shown abnormally high concentrations. I finally found out after 6PM of the night before the scheduled date that all was well and that I was a "go". I asked the oncodoc's assistant MD, who phoned me, what the problem was regarding the spleen and the bone marrow. He gave me an answer that didn't completely satisfy me. So the next morning, we got to the hospital early and I cornered the head of Nuclear Medicine. Inasmuch as I was the first one to go through this trial here, they are learning as they go. (More about this below.) It seems that in the case of the bone marrow, the software used had misplaced a decimal point which gave a reading that was 10,000 times higher than it should have been. In the case of the spleen, a phone call to IDEC revealed that there is a normal, high initial concentration of Indium in that area which later decreases to normal limits. This was confirmed by my last scan on Monday, the day before the schedule Yttrium infusion. In addition, they reviewed my CT and US scans which showed that my spleen was of normal size, in apparent good working order, and eager to get going on this trial. So, all was a "go" -- but a cliff-hanger from start to finish.
7/21/98 The Big Day! Graduation Day! Got to the hospital at 9AM. Got the second and final infusion of Rituxan plus the usual Tylenol plus the usual Benadryl plus the usual gibberish plus the usual beddy-bye. Once again, this took about 3 hours. Then down to Nuclear Medicine again, this time for The Biggie: the squirt of Yttrium. This takes about 3 minutes. Then blood tests 30 minutes later and 1 ½ hours later. And that was it.
7/22/98 There were minimal, if any, side effects to the whole procedure. I experienced insomnia -- but I am a card-carrying Insomniac. I did feel tired for a few hours -- but nothing monumental, certainly nothing at all that compared with my previous 3 courses of CVP. Aside from that, nothing noteworthy. No hair loss, no emotional swings, no nothin'.
Now, I wait for the results. The CT on 8/19 should tell us about that. I am scheduled for further blood tests (I believe I had about 20 during the past 8 days) weekly for the next 12 weeks and CT's in one month and then every 3 months for the next 2 years, etc. I don't mind one bit if they follow me up for the next 5 years -- or 10 -- or 15 -- or 30. I know what the Rituxan+Yttrium is supposed to do. My oncodoc knows what it is supposed to do. My wife knows what it is supposed to do. The nurses all know what it is supposed to do. *You* know what it is supposed to do. I just hope that the Rituxan+Yttrium knows what *it* is supposed to do!
A few observations: 1. If you enter a clinical trial, try not to be the first one in it at your center. There is a learning curve that must be reckoned with * on everyone's part. For many of the personnel, they are sailing into uncharted waters. I wish I had been No.5 in this one instead of riding point.
2. During the course of this protocol, I had:
4 infusions, including 2 isotopes.
2 biopsies (1 nodal, 1 bone marrow)
5 image scans (dosimetry)
About 20 blood tests. I just about ran out of usable veins.
3. Every step of the way, everything was checked by IDEC, some 3,000 miles away. There were frequent conversations between the staff here and the folks in San Diego, making certain that everything done conformed to their criteria. Duplicate blood samples were sent off from Gainesville to San Diego as were all reports, scans, etc. So, they had a very tight rein on all that happened. Nothing really happened without their approval. That gives one a nice feeling of comfort and security.
IDEC Rituxan/Yttrium Clinical Trial follow-up
Date: 98-08-28
Back, about a month ago, I reported on the Rituxan/Yttrium Clinical Trial that I had entered. Several subscribers wrote to me, asking what results, if any, had been achieved. I apologize to them for not having responded sooner but I was waiting for my one-month scans. These were done the last few days and the results came in yesterday. What I have for you is . . .
A MESSAGE OF HOPE for all of us!
The news at this point seems very, very good. Not just for me but for every one of us. This clinical trial wasn't just about me; it was about all of us. Clinical trials provide info for everyone who is similarly afflicted so please regard this one as just that -- as YOUR trial as well as mine.
My oncodoc reports a reduction of 87% in my nodular mass (just about as much portfolio reduction as I'm experiencing in this current stock market decline). Some of the nodes are no longer distinguishable on my CT scan. Others have had very substantial mass reductions. They are all at, or very close to, 10mm in size (the maximum size that would be considered normal under IDEC's standard of measurement). Please note that there are those who regard the 10mm-20mm area as a grey area where a node can still be normal, made up at least partially of scar tissue. By that more generous standard, I would have been classified as a CR (Complete Response), well within the normal range. (I am a very strong advocate of more generous standards and larger normal ranges. Very good for one's morale.)
I had 3 palpable nodes: 1 at my right parotid (jawbone to you), 2 in my left axillary (armpit). These are now completely gone. My largest one, at my left kidney, near the vena cava (that's one of the two pipes that carries blood back to the heart) was previously 18mmx40mm. That one is now 0mmx0mm. Of all 8 nodes that were measured, one is now 12mmx12mm, another is now 11mmx11mm, just an inchy-pinchy above the 10mm cutoff; the rest are all at 10mm or less. So the bottom line is: as close as one can get to a CR without actually being classified as such.
More good news: (1) This protocol works quite differently from conventional chemo. While the latter is fast-acting, showing substantial results in just a week or two, radioisotopes are long acting, achieving most of their results in the first month post-tx but continuing beyond that. My oncodoc's guess is that my 2-month scan will show even further improvement. (2) Inasmuch as my pre-tx bone marrow biopsy showed only 2% involvement, an MCR (Molecular Complete Response) is not beyond the realm of possibility. I'm not sure I can handle that much good news alone; I'll need your support if that comes about. (Note: there is currently no hard evidence of what exactly an MCR means in terms of survival but it certainly is nice to have: like an Oscar, a SuperBowl ring, or an Income Tax refund.)
All this was accomplished without any dire side effects: no nausea, no internal upsets, no hair loss, no nothing. Just a feeling of exhaustion that was of rather short duration. The only unusual thing I noticed was this tree trunk that grew out of my forehead and the irresistible urge to shop at K-Mart. (I'm kidding; I'M KIDDING!)
Some sobering facts: These results will, of course, have to be verified by IDEC's own radiologists but my doc feels that they will, at least, be classified as a very strong PR. How durable a remission this will be is, of course, uncertain. It could be short; it could be long. So I regularly pray to The Supreme God of Lymphoma and place burnt offerings (an overtoasted bagel) on my altar (our kitchen pass-through bar). It's all in his lap now. May he look favorably upon all of us.
Incidentally, you may recall that I had a running debate with my oncodocs about the inordinate amount of radiation I was asked to absorb during this trial and for the follow-ups. (Follow-up is to continue for the next 4 years if remission continues. I've given permission for them to follow me up for the next 30 years. That would put me at close to 110 but whattaheck, anything for Science.) There was nothing I could do about the mandatory CTs, isotopes, and such but I did have great misgivings -- which I misgave in abundance -- about the follow-up CTs every month for the first 3 months and then quarterly thereafter. Here's how we resolved that: CTs and MRIs are both acceptable by IDEC for followup. So I had a CT and an MRI at the same time, to establish a correlated baseline for the MRI. Thus MRIs will henceforth be acceptable for follow-up. All the nodes apparently showed up on the MRI so it should be every bit as effective as the CT. The new MRI currently in use also required no contrast material, either as IV or ingested, was quite quick, and not as hard on the ear drums as previously.
So, please if you find this news to be good, think of it as good news for YOU. We're now seeing new, break-through protocols coming online; MABs are just one of them; there are so many others currently being tested and soon to be available. We read about them all here, on this list. Out there, somewhere, is "The One". I think of the current ones -- like IDEC and such -- as the means to stick around until "That Big One" comes along. All we have to do is hang in there for that happy day. Let's all do it!
If you have any questions about the trial, please contact me via e-mail. I'll be happy to oblige.
I wish you the best of good health.
Expect to win!
Paul Klein © 1998
Written by Vera Bradova © 1998
Updated 9-10-1998
Get your own Free Home Page