FCR therapy comes of age
FCR combination (fludarabine, cyclophosphamide and Rituxan) clinical trials were just getting talked about back in the summer of 2001 when my husband PC was diagnosed. Eight years later, this combination (with a few dosage and protocol tweaks along the way) has become the de-facto gold standard therapy for CLL. One of these days I will review the results of the benchmark clinical trial conducted in Germany. While there are differences in the response statistics between this trial and the results reported earlier by M. D. Anderson, there is no question FCR is a very potent combination that has added significantly to our therapy options.
Anyone out there hoping FCR therapy will actually CURE their CLL, once and for all? Here is a quote from the team that spearheaded the development of FCR regimen at M. D. Anderson:
“The FCR regimen is the most active treatment program in CLL, with 72% of frontline patients achieving a complete remission (CR) lasting a median of 7 years. However, most patients are not cured and will eventually relapse with CLL.”
OK, most patients will eventually relapse. We get it. It is a matter of when, not if. By now enough time has passed since the first batches of patient volunteers have graduated from FCR clinical trials and we can ask the question: what is life like for patients after their hard-won FCR remission ends?
Life after FCR
I have attached at the end of this review an important abstract from ASH 2008 conference that tries to answer this particular question. This is straight from the horse’s mouth as it were, the authors listed are the very folks that pioneered the FCR combination. I urge you to read the abstract for yourself. My two cent comments are below – cheap at the price if I say so myself.
One can argue about the exact response statistics of patients going through FCR as front-line therapy (we discussed some of the reasons why response statistics can vary pretty dramatically in an earlier ‘Updates’ article titled “FCR versus PCR”). But that is not the point of this review. This article focuses on the fate of patients who have already relapsed after their FCR therapy.
This study looks at 97 patients who have completed “salvage treatment” after their FCR remissions relapsed. (I wonder if oncologists know how much that phrase “salvage treatment” sticks in the craw of patients and their spouses).
Who had the best shot with Salvage after FCR relapse?
Turns out this is a no-brainer. While the “median” FCR relapsed patient lived 32 months after completion of salvage therapy, patients who were lucky enough to have good prognostics and therefore responded well to FCR also responded well to salvage therapy after their FCR relapse. Here is how it shakes out:
- Median survival after salvage for the whole group was 32 months.
- Patients who got a CR and a remission that lasted at least 18 months after their FCR therapy did better with salvage therapy too, patients with this ‘good’ profile lived on average for 47 months.
- For the unfortunate patients who did poorly with FCR (only partial response and remission lasting less than 18 months) salvage therapy did not work any miracles either. The median survival was only 13 months.
- M. D. Anderson is a big believer in the prognostic value of beta-2-microglobulin (B2M). Median survival after salvage has not yet been reached for folks with good B2M. Patients with B2m higher than 3.0 did not do well on FCR or subsequent salvage therapy (median survival of 17 months after salvage).
- Also as you would expect, folks with the good IgVH mutated variety of CLL did better with the FCR front-line therapy and also subsequent salvage therapy when the first remission ended.
Moral of the story, if you are lucky enough to have relatively easy going CLL to begin with, if your disease was still relatively early stage when you decided to pull the plug and initiate therapy (good platelet counts, for example), you are more likely to do well on FCR, get a long remission from it, and when you relapse, you are also likely to get good response to salvage therapy and have several year survival horizon to contemplate. Unfortunately, the small numbers of patients whose FISH abnormalities were documented is small, and conclusions drawn on the basis of small groups of patients are notoriously undependable.
A nagging thought at the back of my mind: there has been some discussion that the chemo-naive patients recruited for the early M. D. Anderson FCR trials were not exactly the worst case scenario patients. There have been comments about cherry-picking, leading to better response statistics at MDA than documented in similar studies done elsewhere. Does this mean the salvage therapy response statistics we are discussing here are also similarly over optimistic? Heaven forbid. These statistics are grim enough as they are!
What kind of salvage therapy is best?
If you are like me, you will want to think through a couple of chess moves ahead of time in this deadly serious cancer ‘game’. Assuming you relapse after front-line FCR therapy, hopefully not any time soon, what are your best options for second string salvage therapy?
The patients in this study got a whole slew of different salvage therapies, depending on the judgment of their local practitioners. Out of the 97 patients followed in this study
- 30 patients tried a second attempt at FCR. 17% (5 patients) of these got another CR (my guess is that these folks were among the lucky ones who did well on the first go-around of FCR and tried their luck with a second shot at what worked well before). Not an overwhelming vindication of a second bite at the apple, if you ask me.
- 25 optimistic folks tried single agent Rituxan, and as you would expect, very few of them- only 4% (a single patient) got a CR. Rituxan does not have the oomph needed to treat CLL patients after they have relapsed from high impact chemoimmunotherapy combinations such as FCR. It is in this context that we are placing our hopes on early approval of Humax-CD20.
- 16 patients tried a combination of Campath + Rituxan. This double monoclonal therapy did a bit better, 31% (5 patients) got CR. This makes sense, Campath targets a different marker (CD52) than Rituxan, one that is heavily expressed by all CLL cells.
- Working on the more-is-better approach, 9 patients tried CFAR (Campath + FCR). An impressive 56% of these guys got a CR following this high impact approach.
While the number of patients who tried CFAR as salvage therapy is small (only 9 patients), I am pretty sure the response statistics will prove to be robust, give or take a few percent points. CFAR gave, by far, the highest CR response rates following FCR relapse. But before we celebrate and sign up for CFAR as a slam-dunk choice after FCR relapse, here is the kicker:
“patients who opted for CFAR as opposed to another go at FCR did not get longer remission or live longer following their chosen salvage therapy (30 month remission, 40 month overall survival)”
Perhaps we will glean some statistically significant differences between CFAR and FCR as salvage therapy when we have larger number of patients to compare, and the higher response stats for CFAR will be reflected in longer remissions and longer life. For now, the jury is still out on this question.
Any silver lining for the “salvage” folks?
The above statistics are grim reading for patients who have opted for FCR and now coming out of remission. Based on this credible study, half the patients did not live beyond 3 years after salvage. “None of the regimens showed a significant survival benefit.” is the down-beat assessment of the authors. Can you think of any better reason for looking for options other than the dog’s breakfast of chemo/immunotherapy combinations tried by the patients we have discussed thus far?
The abstract does hold forth a glimmer of hope. 27 out of the 97 patients went the route of getting a mini allo stem cell transplant. Here is a telling quote from the authors:
“Patients receiving Stem Cell Transplant had a significantly superior Overall Survival than those who did not undergo SCT”.
Only 14 out of the full cohort of 97 patients survived more than 4 years. Of these, a large majority (11 out of 14 – a whopping 79%) had chosen the transplant route. In fact, the median survival has not yet been reached in patients who chose to get a stem cell transplant, compared to a mere 30 month overall survival for those that did not.
Editorial
Forgive me for putting this picture in blunt terms. Here is a potential scenario:
You have had FCR. You had a nice remission. Like all good things, it has come to an end. Now you need to do decide what to do next. You want to live more than 4 years? Your odds of doing so are 79% if you go for a transplant, and only 21% if you choose some other salvage therapy – statistically speaking.
Aha. There is that sneaky little phrase, statistically speaking. Any one of us can have outcomes that are not predicted by statistics. They can be much better than predicted or much worse depending on your individual case. The horse that is given the poorest odds of winning the race can still win, make you rich beyond your dreams. Or the nag can come dead last. But given the choice of betting on only one of the horses in the race, with your life on the line, do you think you should bet on the horse with the best statistics, the one most likely to win the race?
I will be the first to admit, stem cell transplants are tough love. Luck plays a significant part, starting with finding a suitable source of stem cells (adult sibling, matched unrelated adult donor, matched cord blood – these are your three choices).
Even mini-allo transplants are not all that “kind & gentle”. Older patients with health problems other than the CLL carry additional risks. The procedure costs an arm & leg, not to mention other bits of you – unless you have good insurance coverage. Not to be glossed over, it requires strong family support – patients will need 24/7 devoted care from a dedicated caregiver for several weeks. “Harvey’s Journal” highlights some of the issues, including the heartbreak of devastating failure even with the best of efforts and planning.
Should you opt for a stem cell transplant after FCR remission comes to an end? Perhaps you will get lucky with the far less risky CFAR, or even a repeat FCR combo? Only you can make that decision.
No one in their right mind would consider a transplant if there were better ways of staying alive. The fact that you are even thinking about this option says you have the proverbial cocked gun pointing at your head. The prudent thing to do would be to learn as much about it as you can ahead of time, get your ducks in a row. Our flagship website www.clltopics.net carries several detailed articles on what to expect. This is your body, your life. I can try to provide a CLL “Owner’s Manual” of sorts, but only you can make decisions that are right for you.
And oh yes, I heard recently from “Richard” of our Catch-22 article fame. He and his wife are enjoying a second honeymoon. With his very aggressive CLL profile I doubt he would have had this chance but for the mini-allo MUD transplant he had early in 2008. For every “Harvey” that did not make it, there are “Richard“s out there that did. What you read into these case histories depends on your personality, your specific situation, your resources.
Life after Fludarabine, Cyclophosphamide, & Rituximab (FCR) – the Clinical Outcome of Patients with Chronic Lymphocytic Leukemia Who Receive Salvage Treatment after Frontline FCR
Sunday, December 7, 2008, 6:00 PM-8:00 PM
Constantine S. Tam1, William G. Wierda, M.D., Ph.D2, Susan O’Brien3, Susan Lerner3*, Issa F Khouri4*, Hagop M. Kantarjian3*and Michael J Keating, M.D.3*
1Haematology, St Vincent’s Hospital, Fitzroy, Australia
2Leukemia, UT M. D. Anderson Cancer Center, Houston, TX
3Leukemia, UT MD Anderson Cancer Center, Houston, TX
4Stem Cell Transplantation and Cellular Therapy, UT MD Anderson Cancer Center, Houston, TXThe FCR regimen is the most active treatment program in CLL, with 72% of frontline patients achieving a complete remission (CR) lasting a median of 7 years. However, most patients are not cured and will eventually relapse with CLL. In order to evaluate how these patients should be subsequently managed, we analyzed our institutional experience with 300 patients treated with frontline FCR (Blood 112:975). After a median follow-up of 6 years, 116 patients (39%) had failed FCR therapy with 13 primary refractory disease and 103 relapses from partial remission (PR), nodular PR (nPR) or CR. Compared with patients in ongoing remission, relapsed / refractory patients had more adverse baseline characteristics including a greater proportion with performance status ≥1 (71% vs 53% p=0.002), elevated β2m (54% vs 36% p=0.002), white cell count ≥150 x 10^9/L (25% vs 12% p=0.003), unmutated IgVH (81% vs 44% p<0.001) and ZAP-70 positivity (78% vs 49% p<0.001). The aim of the current analysis was to determine the duration of survival (OS) following second-line therapy in 97 patients who had completed salvage treatment. The median follow-up was 32 (range 3 – 69) months, and the median OS (mOS) was 32 months. Characteristics associated with favorable OS were: (1) previous best response to FCR of nPR/CR lasting ≥18 months (mOS 47 months, vs 13 months for primary refractory disease, PR or nPR/CR lasting <18 months p=0.002); (2) β2m < 3.0 mg/L (mOS not reached, vs 17 months p=0.0003) and (3) platelets ≥ 100×10^9/L (mOS 47 months, vs 15 months p=0.004). Poor risk cytogenetic abnormalities were common at FCR failure: among 38 assessable patients, 7 (18%) had 17p- and 18 (47%) had 11q- by conventional karyotyping and/or FISH. Although patients with 17p- or 11q- had an inferior survival, this survival disadvantage was confined entirely to those who also had an elevated β2m ≥3.0 mg/L. Surprisingly, patients relapsing after durable FCR remissions (≥5 years) and patients with slowly progressive relapse (time to salvage ≥12 months after FCR failure) had similar OS as their more adverse counterparts (p=0.76 and 0.86 respectively). A prognostic model comprising β2m and platelet count effectively divided patients into low, intermediate and high risk categories with mOS of >45, 32 and 13 months respectively (p<0.0001). Patients received treatment chosen at the discretion of individual treating physicians and the CR rate of second-line therapy were: FCR (n=30), 17%; rituximab (n=25), 4%; alemtuzumab ± rituximab (n=16), 31%; FCR & alemtuzumab (CFAR, n=9), 56%; lymphoma-type chemotherapy (n=5), 0%; other treatment (n=12), 0%. The CR rate for CFAR was significantly higher than that of FCR (p=0.03), although the median remission duration (30 vs 20 months) and OS (44 vs 32 months) were similar (p=0.87 and 0.51 respectively). None of the regimens showed a significant survival benefit. Allogeneic stem cell transplantation (SCT) was performed in 27 (28%) patients at a median of 15 months after first salvage. Patients receiving SCT had a significantly superior OS than those who did not undergo SCT (not reached vs 30 months, p=0.03). Of the 14 patients surviving for more than four years, 11 (79%) had undergone a SCT. Patients who fail FCR therapy had high risk disease features including elevated β2m, unmutated IgVH and ZAP-70 positivity, and most had adverse cytogenetic findings at relapse. Results of salvage therapy in this group were poor with a median survival of less than three years. The majority of long-term survivors had received allogeneic stem cell transplantation.
26 comments on "Life after FCR"
I wonder how many of these patients would still choose FCR had they known then about these unhappy post-FCR prognoses.
We are often forced to decide between the devil and the deep blue sea.
Compared to the toxicity versus remissions obtained with older chemotherapy drug regimens, FCR has proven to yield substantially better (longer, fewer adverse effects) remissions. I guess we have to be grateful for small mercies.
The recent German study comparing FCR combination against older combination of FC is very illustrative of the value of adding Rituxan to the mix. FCR proved to be better than FC on just about every count. So much so that I understand the European Union has finally seen fit to approve R in combination with chemotherapy as an approved drug for the treatment of CLL.
How do we go about CURING CLL, not just driving it into a remission that is destined to fail, sooner or later?
Allo transplants are the only curative option at this time. We need an active immune system (the new graft), a cellular therapy to do a house-to-house search for each and every terrorist cancer cell in the body, and keep doing it for as long as it takes to make sure the cancer does not have a chance to regroup and raise its ugly head once more.
But stem cell transplants are hardly an easy therapy option. Replacing one’s home grown immune system with a foreign one is an extreme choice, a bit like asking a neighboring country to invade with its killer-troops because we have a home grown terrorist problem that we cannot handle our self. How do we get rid of the foreign troops once the problem is fixed? OR do we have to live with the invaders for the rest of our life?
Here is the scenario that several experts suggested will eventually be developed to CURE CLL without the drastic step of replacing the whole immune system.
Step one: a robust chemo-immunotherapy combination (FCR is a good start on that front) to reduce the tumor load to as low level as possible, a pcr negative remission.
Step two, an active cellular therapy that can do the house-to-house search and destroy mission to mop up any remaining traces of cancer. The trick is to achieve cellular therapy that eventually fades away, leaving behind your original immune system (no risk of long term GVHD that is almost inevitable with a foreign immune system permanently in place).
Step three, repeat as necessary to get the job done!
We are just seeing the opening salvos on this approach, as in the haplo NK cell study we described on our website a few months back. This involves massive FCR type pre-conditioning to get deep tumor load reduction, followed by haplo (only partly) matched NK cell infusion to carry out the cellular hunt for remaining stragglers. The haplo NK cells fade away after a couple of weeks, hopefully after finishing the job. The good news is that with a little practice researchers can hope to learn how to repeat the process until an actual CURE is established. The other good news is that almost everyone has suitable haplo donors available, if they have kids.
If this approach makes sense to you, consider participating in the haplo NK cell study being conducted at the University of Minnesota. Write to me if you want help in contacting the researcher conducting this trial. This trial represents cutting edge combination of chemo-immunotherapy with cellular therapy backstop – possibly the best combination I can think of.
I’m getting ready for Round 4 of FCR – Bulky nodes forced treatment. Nodes have disappeared, very few side effects, but the efficacy as yet undetermined. Testing after Round 4 should determine if there are rounds 5 & 6.
I’m happy with my choice. I’ve got cancer for crying out loud. I’ve seen, first hand, the side effects treatment for rectal (neuropathy, incontinence), ovarian cancer (death) and brain cancer (death). We didn’t exactly draw the short straw here. I’ll take my 7 year remission and few side effects… I win. Who knows how SCT will have progressed in 7 years, not to mention drugs in the pipeline. I’m considering the Bexxar trial when I’m done. Maybe we can turn 7 years into 10… or more! Let’s play the hand we’re dealt as best we can. We’re fortunate to have the options available we do.
That said… thank God for this site and the folks involved (especially you Chaya). I wouldn’t have understood the ramifications of my treatment choice without your guidance and support. I’ve gone in with my eyes wide open and I’ll accept whatever fate befalls me. Thanks to all of you, I understand what I’m doing and why.
Chaya,
As you noted, the Abstract begins with:
“The FCR regimen is the most active treatment program in CLL, with 72% of frontline patients achieving a complete remission (CR) lasting a median of 7 years. However, most patients are not cured and will eventually relapse with CLL.”
This leave me with two questions, if you know the answers:
1. What kind of CR are they referring to? Are these patients MRD negative? (I am 20 mos out from FCR with what I think is a four or six-color flow MRD negative CR–and doing very well.)
2. I see the “most patients are not cured” comment and can’t help but wonder if the MD Anderson folks are still claiming cures with FCR? (For what it’s worth, I had a transplant specialist at Shands in Gainesville, FL tell me point blank last April that they get cll cures with transplants.)
TPO4444, Burke
You guys are my kind of patients: smart, pragmatic, willing to look the situation straight on and make the best decisions open to you. In addition to cytogenetics, I am convinced personality traits are equally important in defining prognosis.
Burke, my sense of it is that no one is cured by FCR; it is truly a matter of when and not if. But that said, to echo TPO4444, if the “when” is 7 or 10 or more years of trouble free remission, what is not to like? How long does a remission have to last before it is a cure, before patient dies of something else and therefore lived out his natural life? Let us not discount the value of FCR – it is powerful chemoimmunotherapy regimen.
Most of you have seen the standard survival curves in articles. The curve starts at time zero with 100% of the patients alive. As time progresses and patients die, the curve starts its sad journey downwards. The million dollar question is this: does the curve ever flatten out or does it continue its depressing downward trend until the percentage of surviving patients gets to zero – just a matter of when and not if?
No chemotherapy regimen (including FCR) has been able to demonstrate a flattening of the curve. In other words, none of these chemo combos have demonstrated a point where no more patients are dying, the ones still living in remission after the therapy in question continue to do so, indefinitely. This flattening of the survival curve is the Holy Grail; it is the first indication that at least some of the participants have actually been cured. Even autologous stem cell transplants (where the patient’s own stem cells are collected for later transplant) do not show this all-important flattening of the survival curves.
The ONLY therapy option open to CLL patients at this point in time that actually has this flattening of the survival curve, demonstrating a point where patients stop dying, is an allogeneic stem cell transplant. That is why I call the “The only CURE”. You can look up an article with that title on the CLL Topics website.
So, why don’t people jump into a transplant right away, as soon as they are diagnosed? Because a good 30% (or more) of the patients will die quickly soon after transplant, due to TRM (treatment related mortality). And going through a transplant is not for the faint of heart. Until and unless mortality statistics improve and we get a better handle on GVHD complications, transplant decisions continue to be very tough ones. Do you want to take 30% chance of dying right away, within months, for a 70% shot of getting the CLL monkey off your back? That is not an easy choice. Without going the transplant route, patients will live for several years (the average life expectancy for CLL patients is around 8 years). A bird in hand versus two in the bush sort of choice.
By the way, most reputable transplant centers will NOT accept newly diagnosed patients. Most require that patients have tried other approaches first. Not only is this prudence, it also reflects good science. We discuss many of the issues in the “Catch 22” article on the CLL Topics website.
Chaya,
I am about to start a regimen of PCR with Lenalidomide after that (phase II clinical trial).
I’ve read your January 2006 FCR vs. PCR article and recognize that it was difficult to come to accurate conclusions at that time.
I’m wondering if there is any updated information comparing the two?
Thanks
Unofrtunately, the article we discussed in the recent Updates review is the one and only comparison between FCR and PCR, head-to-head.
I have heard from several researchers that this was a poorly conducted trial, that actual response statistics for both FCR and PCR are better than this, even in community practice. I tend to agree with that assessment.
The conclusion that this perhaps flawed study underlined that is harder to dismiss is that PCR is no kinder and gentler than FCR. For the same bang, it seems to me the price tag of toxicity and adverse effects are roughly the same. Bummer.
In your case, you are looking at PCR + lenalidomide (Revlimid). That is a whole new kettle of fish, no one can say ahead of time how this would pan out. My guess is that they are looking for a CFAR type response (CFAR = FCR + Campath). Front-ending with PCR would bring about very substanatial reduction in tumor load, and that would greatly reduce risk of “tumor flare” reaction with Revlimid.
It is an interesting clinical trial and I would like to know more about it. I will be pleased to review the protocol for our members if anyone out there partcipating in the trial is willing to send me the trial protocol. I understand a similar FCR + Revlimid trial is getting underway. Some day it will be instructive to see how these two paralell approaches pan out.
Chaya,tpo4444
We are getting ready to start FCR at a local hospital. The Dr. said today worried about cells dying too fast and may cause kidney damage. Is the FCR worth it? So they will hospitalize for the first treament. Do you function while on this stuff? I want him to get used to drinking alot of water. will this help. We are not finding too much out like could you still work? are you wiped out for weeks at a time? Dr. seems to act like a walk in the park. I have read this site often. chaya, you have done more for cll people then you every will know. Steve
FCR is not a walk in the park. Some patients have an easier time of it than others. I have heard of patients who continued working through the entire process, while others needed to take time off. It seems to depend on the individual patient. Prudence requires that you should be prepared for either contingency.
As for the issues related to potentail kidney damage due to cancer cells getting killed too quickly, this is called “Tumor Lysis Syndrome” and we published a full length article on the subject a few days ago on this site.
Another thing to remember, please make sure your doctor is aware of the need for prophylactic medications to protect the patient from a variety of opportunistic infections while undergoing FCR therapy.
I had a problem with Tumor Lysis Syndrome during my FCR. Five days after I finished my first cycle, I was called by my doc and told to go to the ER because a blood test I had taken that morning showed that my kidneys were about to shut down. I spent two days there getting flushed out with “Bi-Carb,” I believe they said it was. Immediately following my second cycle, they admitted me also, and I spent another couple of days there.
I consoled myself by telling myself that the TLS at least meant that I was killing a lot of cancer cells, although the nurses emphatically told me that there is nothing good about TLS.
Whatever.
I’m in CR (MRD negative) after only 4 cycles. And my fludarabine dose had been slightly reduced because of my age. And I had had bulky disease, 70% marrow involvement and a spleen the size of a partially inflated basketball.
The stuff didn’t kill me, and it did kill an awful lot of cancer cells. I can live with that.
Kudos to the nurses, I most sincerely agree with them; THERE IS NOTHING GOOD ABOUT TUMOR LYSIS SYNDROME.
Burke, you were lucky you had a doctor’s office that was on the ball, recognized the emergency nature of the lab test results and responded appropriately. Tumor Lysis can make patients dependent on dialysis for the rest of their lives, it can and does kill patients – very quickly.
Next time around, do kill CLL cells but without all the drama of tumor lysis, OK?
I’ve been trying to find more information on the results of FCR lite. What I’m reading indicates that this is as effective as FCR but with much lower side effects.
I’d appreciate your research on this. You do a much better job translating to lay person speak!!!
Thanks
Dr. Kenneth FOON of FCR-Lite fame has moved from University of Pittsburg Medical Center to head the department at the Nevada Cancer Center. I am fortunate to count him in my list of good friends and collegues. The latest results on FCR-Lite have been published in a very recent Journal of Clinical Oncology article – and I am part way through reviewing it for our members, one more item on my to-do list
I hope most of you have not realized I have been away from my desk at Sedona, AZ. I have been on the road, visiting my mom in India. Amazing what one can do from across the world these days. I will be back home in little over a week and have much better internet access.
oopppsss I didn’t see this until after I wrote to you on the other topic. I thought when I talked to you last that you were going to be home on the 4th…oh well obviously we can NOT tell that you are away from your desk! Technology is truly a great blessing at times. I am looking forward to hearing what you think regarding FCR-Lite. It seems that we may have to step up our plans for starting treatment for my husband. So I am stepping up my research. Have lots of questions for you when you get back.
April
My husband, Tom, was part of the FCR3 trial at MDACC. I believe at first there were 326 patient’s enrolled. Down to 300 when Tom started in April, 2004. Tom had all prognostic tests done before FCR. Normal karyotype, CD38-, unmutated using VH3.21 gene, Zap70+ at 40%. He was one of the patient’s who continued working through treatment. He travels the country by plane every week to do TV commercials. MDAnderson was pretty blunt about the fact that he should not be flying during FCR because of the risk of infection. But, for Tom, this was not an option because he needed to keep working. He had the normal side effects with FCR–nausea, platelets below 100, feeling off for the first week after treatment and then climbing back to feeling pretty darn good just in time for another round of infusions. After the 5th month, he was working in Houston–(thank goodness), spiked a temp of 102 and was put in the hospital at MDACC with FUO and no way to stop his crashing WBC and neuts. I was told by Dr. Keating that Tom had a 50/50 chance of making it through. 3 days later, he was back on the road. That was the only time he missed work during the protocol. Tom finished FCR in November of 2004 with an nPR–MRD positive and nodules in the marrow. In the following year, Tom became CD38+ in the 20% area.
December 2007 began Tom’s relapse. Swelling lymph nodes and numerous infections of the upper respiratory system. February he started Rituximab as a band-aid effect until the FDA approved Revlimid for trial at MDACC. Every month, he had to have numerous infusions of Rituximab to keep his CLL in check. One month off and he would skyrocket back to being pretty sick. During this time, not only did Tom keep working but we also had a wonderful family trip to Barcelona. Tom was on antibiotics and had the name of a great CLL Dr. in Barcelona–just in case. Tom began the Revlimid/Rituximab trial for relapsed, active CLL patient’s at MDACC in December 2008. New FISH showed that Tom picked up the TP53 deletion in March of 2008 and in December of 2008, he also showed deletion of both D13S319 Loci. Also, Tom showed CD38+ at 45% now. At dx. he was only CD38 at 3%…quite a change. 2 months into Revlimid and Tom had the sunburn rash and the treament stopped for 2 weeks. He is slowly increasing Revlimid at this time.
The main question I see here is, “Is FCR worth it?” That all depends on how you view life and living. Tom will always be a trial rat because we know that is how the cure will be found. If he isn’t one of the lucky one’s to be cured, he will be happy in the fact that his willingness to be a rat just might save patient’s in the future. Tom is one of those personalities that just cannot sit around the house and not work. For him, a transplant represents an end of the way he wants to live his life. We would do FCR all over again if faced with the same situation and time frame. It gave Tom a fantastic remission and joy of living for almost 3 years. He’d rather have that then years of just hanging on in hopes of getting good health back one day. Did the FCR cause his clonal evolution? Perhaps. But with CLL the best thing to learn is that you CAN NOT cry over spilled milk. We are lucky. We have gotten to live the life that dreams are made of. I believe that without FCR, we would not have had one of our best memories….Barcelona with our son’s.
I am rather hard set in my opinion about chemotherapy and the joy of getting some really great years to enjoy life. I have had too many friend’s watch and wait too long and in the end, not only was their life one of being bedridden, but they ended up losing this battle because their CLL had ramped up. And this happened without any involvement of FCR.
We can only do what we think is best at the time. No one can do better then that.
Jenny Lou
Jenny,
Thanks so much for sharing. This is exactly the kind of stories I was hoping to see on this site. With enough of them patterns will emerge and we will have our own little clinical trial and treatment reviews going. It helps so much for those of us out here trying to get unbiased treatment choices. Thanks and God be with you and your family.
April
Hello,
Chaya I have been so helped by these articles. And all of you for sharing I give a hearty thank you.
I am to start FCR next Wed. Feb. 25, 2009. I have had CLL now since 2004 Oct. I was in a clinical trial at Mayo using EGCG and was extremely encouraged by some results until I had stomach problems from too much EGCG and had to discontinue.
I have no real symptoms other than anemia and low platelets. My local doc said that he wanted to use just Rituximab but my Mayo Doc suggested the FCR.
You have given me much to think about.
Kind regards,
Mark
Mark, please keep us posted on how you are doing. We are also about to embark on this path. God bless you, chaya and the many others who are so dedicated to helping CLL understanding. Steve
Chaya, your postings are amazing and so informative.
My husband Doug is about to undergo his 3rd round of FCR – he was originally diagnosed in January 1996 and commenced Cyclophosphamide & Rituxan treatment in 2003. This was followed up with maintenance Rituxan on and off for a couple of years and for the past twelve months has been having IVIg infusions monthly. With now undergoing FCR, is this considered salvage treatment? – I am concerned that if he doesn’t get a long remission from this that the outlook is not good.
Gwen:
“Salvage treatment” is just one more label. How Doug responds to FCR is determined by a lot of stuff that is unique to each patient. He has already beaten the odds, at 13+ years post CLL diagnosis – the median overall survival for CLL patients is 7-8 years. My advice to you is simply this: enjoy each day, help your husband stay as healthy as he can on all other things that are within your control, and never, ever, waste time second guessing your decisions. You guys have done great thus far!
Thank you Chaya – the only other thing that he really has trouble with are melanomas which he is constantly having to have removed. He has kept relatively well except for the odd hiccup with a unexplained virus a couple of years ago, a splenic infarction – fortunately they didn’t have to remove his spleen as he recovered ok, and an attack of deep vein thrombosis. When he was first diagnosed Doug was 53 his then Oncologist (who has since retired) said if he got to 70 he would have had a fair go – he was 67 last August, and we find it hard not to look at the calendar when he has had more frequent trips to hospital in the last two years than he has had since diagnosis. We try to remain positive. Again, thank you for your comments, it is good to know that he is not one of the average survivors…..
Hi Chaya,
In one of your comments you mentioned:
consider participating in the haplo NK cell study being conducted at the University of Minnesota. Write to me if you want help in contacting the researcher conducting this trial. This trial represents cutting edge combination of chemo-immunotherapy with cellular therapy backstop – possibly the best combination I can think of.
If this study is still going, I’d like to investigate. If you could provide a contact, I’d greatly appreciate it.
Thanks
Pllouwagie:
I am sorry to report that the results of this study were not as good as I and the researchers hoped. The precious haplo NK cells infused into the patient did not survive long enough to do the necessary amount of graft-versus-leukemia. I am told they are trying different techniques to try and get around the problem.
History of medical research is full of ideas that sound exciting, that don’t work out at first blush, but sometimes repeating the experiment with new twists learned from prior failures makes all the difference. It is a slow and often times frustrating process.
I am late in commenting on this topic but my Father who is now 74 was treated with FCR 5 cycles ending January 2009. He has started showing signs of relapse.
The Oncologist informed that one should also remember that the patient is older than when he was treated first and the age factor is very important.
He suggested Chlorambucil or Revlimid rather than FCR. Though he did well with first round of FCR, the age factor has to be taken into account.
Any comments on the same?
hitenge:
If you browse through my second workshop slides and comments published on this site (“Everything you wanted to know about FCR”), age is clearly cited as one of the possible contra-indications for FCR therapy. Your father’s oncologist is right to consider that,
Chaya – I was diagnosed 11/2011 at age 49 and have been reading as much as possible from that point forward. Thank-you for all of your efforts on this site btw – but I am struck by the fact that the studies (or summaries I read) don’t seem to stratify for age. Is the life expectancy different for younger diagnosed patients? My indicators are good – mutated, 13q deletion, borderline positive Zap-70, etc. Theoretically I am one of the lucky ones. At age 50, however, I wonder what that means. Since this was traditionally thought of as an “old man’s disease”, I am always hopeful that the statistics are skewed due to typical age-related factors. Am I being too Pollyanna? Is it realistic to hope for an indolent disease that allows for the development of medications that some day will make this a manageable “condition”?
The timelines from the above (somewhat dated) article – while probably encouraging for someone at the stage of treatment – are not very encouraging for a 50-year old with asymptomatic disease.
thanks,
Dave
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