Miss me?
Finally, after the usual quota of snafus, I am settling down in my new home in Columbia, Maryland. There are still a few unpacked cardboard boxes lurking around but the major headache of moving hearth and home is now behind me.
I hope you enjoyed your break from reading Updates about our favorite “good” cancer, because the next few weeks are going to be busy ones for you and me. The American Society of Clinical Oncology (ASCO) 2010 abstracts have been published online and there are a lot of interesting CLL papers presented. Here is the first one of the bunch that I will be reviewing for you.
FC versus FCR
It is official. There is no further justification for treating late stage CLL patients needing therapy with FC (fludarabine + cyclophosphamide), when FC+R is so much better. We are not talking about just response rates that researchers seem to find so fascinating. What impresses me is how long the remissions last (progression free survival or PFS) and how long patients live (overall survival OS) after completing therapy. Judging by both of these crucial metrics, patients do much better when treated with FC+R instead of just FC.
As you would expect, this important paper comes from M. D. Anderson, the center that has done the most work to establish FCR as the present day gold standard for treating CLL (both as front-line therapy as well as second line or salvage therapy). The full length ASCO abstract is given below for your convenience.
You should be aware this is not a double arm study done with patients randomly divided into the two protocols. Basically, the researchers compared their FCR clinical trial results with historical data available about how patients respond to FC. There can be inherent apples versus oranges problems associated with such comparisons. But it is the best we have, for now. The differences in response results are striking enough to wash over any minor discrepancies between the two groups.
The researchers point out that earlier studies have shown the advantage of FCR over FC in early stage and untreated patients. This study looks at late stage (Rai Stage III or IV) untreated patients. The two groups of patients are reasonably well matched, more or less. That makes the job of comparing the results a little bit easier.
Longer Lives, Longer Remissions
Please pay particular attention to the last four lines of the table at the end. The overall response rate was significantly higher with FCR (92% versus 79%). But even more telling, the percentage of patients getting the coveted “CR” (complete response) was more than double with FCR (66% versus 29%). That is a huge difference, and if you happen to be interested in statistical significance, the p value of 0.000 confirms it is indeed very, very significant.
But for patients and their families, what really matter is how long the hard won remission lasts, how long the patient lives after completing therapy. In the case of FCR, the median length of remission was 79 months, compared to 36 months for FC!! For a change, we have overall survival numbers too. Patients undergoing FCR therapy lived for median of 120 months (put in different words, half the patients lived more than 10 years). Compare that to the fact that the median overall survival was only 55 months for those undergoing FC therapy!! That is a whopping difference of 65 months or just under 5 ½ years!
Comparison of fludarabine (F) plus cyclophosphamide (C) versus FC plus rituximab (R) in previously untreated Rai stage III/IV chronic lymphocytic leukemia (CLL).
J Clin Oncol 28:7s, 2010 (suppl; abstr 6519)
Abstract No: 6519
Author(s): S. A. Parikh, W. G. Wierda, X. Badoux, S. M. O’Brien, A. Ferrajoli, S. Faderl, J. A. Burger, S. Lerner, H. Kantarjian, M. J. Keating; University of Texas M. D. Anderson Cancer Center, Houston, TX
Abstract:
Background: A phase III study showed that treatment with FCR was associated with significant improvement in progression-free survival (PFS) and overall survival (OS) compared to FC in previously untreated patients (pts) with CLL. This benefit was clearly demonstrated for pts with Binet stage A and B; but was less clear for pts with Binet C disease. We report a historic comparison of pts with Rai III/IV CLL treated with front-line FC versus FCR at our institution. Methods: FC consisted of F: 30 mg/m2 and C: 300 mg/m2 on D1-3 ± GM-CSF 275 mg/m2 daily, every 4 weeks for 6 courses. FCR consisted of F: 25 mg/m2 and C: 250 mg/m2 on D2-4; R: 375 mg/m2 on D1 (for the first course) and 500 mg/m2 for courses 2-6, every 4 weeks for 6 courses. Indications for treatment and response assessment were according to 1996 NCI-WG guidelines for both groups. Results: Of 93 pts treated with FC, 38 (41%) had Rai III/IV CLL; and of 300 pts treated with FCR, 102 (34%) had Rai III/IV CLL. Baseline characteristics, complete remission (CR), overall response rate (ORR), PFS and OS of Rai III/IV CLL pts are shown (Table). There was a higher incidence of grade 3/4 neutropenia and thrombocytopenia with FCR compared to FC; however there was no significant difference in infectious complications between the two treatments. Conclusions: In pts with previously untreated Rai III/IV CLL, FCR was associated with significantly improved response rates and survival compared to historic patients treated with FC.
Don’t Get Stuck With the Short End of the Pointy Stick!
You see what I mean by saying there can be no further justification for using FC as frontline therapy in late stage patients needing therapy. FCR is clearly better, and everything I know about these two protocols says there is no additional increase in toxicity by the addition of Rituxan to F+C.
So, why do some patients still get treated with FC, even after the jury is in with the verdict? I can think of two reasons. The first reason has to do with money. Rituxan costs significant money. FC is a whole lot cheaper than FCR. I don’t want to get into politics of health-care or who pays for stuff – we follow a strict policy of no political discussions on this website. But this much is obvious to all of us – money makes the world go round and costs do matter. Eventually, consumers pay for everything, one way or another, through our taxes and our insurance policies.
The second reason why FC may be recommended is even more heartbreaking. Crucial information like this takes time to percolate down to the level of the local oncologists. No researcher at M. D. Anderson or any of the other expert centers would dream of using FC as front-line therapy any longer, not when FCR is available. But what about the strip-mall oncologists (you know, the guy who hangs out his shingle next door to the hair salon) who does not bother to attend ASH / ASCO, does not take the time to read articles in professional journals, the guys who make no effort to keep up to speed with new developments? Back when he went to medical school, FC was the standard of therapy and as far as he is concerned, what was good enough 20 years ago is good enough for today’s patients (Not!)
Don’t get me wrong. There are plenty of hard working local oncologists who make every effort to keep up with things and I take my hat off to these good professionals. I am talking about the ones that do not make this effort. If you have no choice but to be treated by such an oncologist, your protection lies in keeping up the learning curve yourself, so that you can educate your physician. I think of this as CME (Continuing Medical Education) from the bottom up, patients bringing their physicians up the learning curve when it becomes necessary.
If you are a late stage CLL patient looking at your therapy options and your guy tells you the best option is FC, please tell him you would rather have FCR. Or the FC+O combination, where the new monoclonal antibody ofatumumab (also known as Arzerra, Humax-cd20) replaces Rituxan. While ofatumumab has far less track record than Rituxan and that is an issue worth remembering, there are some reasons for hoping that being a fully humanized antibody, ofatumumab may have fewer adverse effects and may have higher efficacy. As you probably know, Rituxan has snippets of mouse protein in it and some patients develop hypersensitivity to it. My husband PC was one of them. Back then we had to go to the UK to get access to ofatumumab. Now that the FDA has approved it, patients can get access to it in the comfort of their home towns.
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36 comments on "FC versus FC+R"
Thanks for this crystal clear summary, and welcome to Maryland.
Shelia
Gaithersburg, MD
Thanks Chaya – good to know, as someone who has been treated with FCR!
Here’s to your new home being everything you hoped it would be – and by the way, we’ve still got a load of those boxes still full in the garage 3 years after moving to Cornwall!
I am so glad you are back and also settled into a new setting. I was just looking today to see if I had missed anything. All of this is such excellent information for us out here in the cyberworld. Hope all is well
Chaya:
First of all “welcome back”! We missed you! glad your move “back east” went well and you are now getting settled and are publishing once again! Great article and very useful information/data – as always!
With the fcr- lite protocol that i was on 4 + years ago, the rituxan treatments were to continue for two years after the end of the fc treatments (which were for 6 months). Unfortunately, i had very bad reactions (including becoming neutropenic) after each of the first two “solo” rituxan treatments. after my oncologist consulted with Dr. Rai about my situation, the two of them, along with my wife and i made an informed decision to discontinue the rituxan treatments for the remainder of the 2 years. thank god, i am still in complete remission. the “only” effects of the treatment was that my immunoglobulin levels were (and continue to be) severely suppressed and I continue to receive ongoing IVIG treatments every 4 to 6 week.
Thus my questions:
1. Are you aware of any studies, or preliminary results, that indicate a better “survival rate” (the listed in this article) if the rituxan is continued for 2 years (on a quarterly basis) after the completion of the f & c?
2. Also, if, or when, i come out of remission, as i had a very bad reaction to the rituxan – are there (yet) any studies regarding the use of ofatumumab and/or the side effects?
Once again, thanks so much for your dedication to “our cause” and welcome back!
Thanks
Alan
Pittsburgh, PA
Afternoon, Chaya…
Welcome back to updates, and welcome to the great North East! I have a couple of friends who live near Phoenix and are thinking of moving back here as well..they miss the snow and the families they left behind to go out there. Get your snow shovel yet?
To your report…great news!
And, even though I had PCR and not FCR, it’s good to know that the “R” I had may mean something. Over two years now since I finished my treatment, and still going strong…was painting my plane this afternoon. With these results, I hope to stay healthy enough to able to fly it soon!
Some terms I am not familiar with in that table. I understand the reference to the four 11q del patients listing (I are one) but why is that mentioned separately where there is no specific mention of having included 17p or 13q patients? Or is that included somehow in one of the other words (diploid, complex, other). Also, was the +12 reference for “12 trisomy”? They add up to the 85 for the FCR, so I imagine they are all included their somehow.
Harley
I recently started a clinical trial treatment for CLL with PCO at Duke. P is the rough equivalent of F. C is the same chemotherapy drug. And O is a replacement for R, and I am told that it has more ways of killing bad cells than R. So far, the results have been impressive. After the first treatment, there were no bad white blood cells found in my blood – and I started treatment with 277 as the white blood cell count. I am now 5 and holding. After the second treatment, all symptoms associated with lymph nodes and spleen were gone -Doctor Lanasa recorded zero – and he indicated that his other clinical trial patients are seeing similar results in the blood and lymph nodes. I seriously doubt that anything new will occur as a result of the recently done third treatment of a six treatment series. Frankly, I am not sure why I even need six treatments if there is nothing to be found. Why not do a bone marrow biopsy now to see if I am CLL free? Oh, let me point out that each treatment is given on a single day and runs about 6 to 7 hours altogether when you add in the initial preparations – anti-nausea, benedryl and a steroid.
How about side effects. So far, the only thing that seems to give me a problem is the neulasta, a shot given 2 days after the chemotherapy to boost the immune system. I get very tired and then 12 hours later quite queasy. I take Ativan and an anti-nausea drug to knock down the queasiness. So far, I only had one treatment related side effect and that was the shakes during the first treatment which was immediately handled with warm blankets and a shot of morphine. The treatment is easy and I often sleep for periods of time. The entire post treatment set of side effects basically disappear in 5 to 7 days but I certainly could not play a couple of sets of tennis, a sport which I truly enjoy playing.
I am pleased to see Chaya’s summary as I think it not only accurately reflects the significance of FCR but shows that the approach I am taking with my clinical trial should yield similar or even better results. By the way, I am 68 and started the treatments on 1 April – yeah, I know, April Fools day.
Chaya,
Because it is so rare to get clarity on anything on CLL, it is especially sad that when the evidence mounts that we have a clear winner, it is not acted on consistently.
One other reason perhaps for not adding R- It needs to watch more closely in the chair by the infusion team with a higher risk of infusion reactions, annoying for both the patient and doctor, but usually just a bump on the road to remission.
Be well
Brian – pondering my next move with my CLL/ITP
cll:
My guess is that addition of Rituxan maintenance will lengthen duration of remission – but I do not remember seeing solid clinical data to that effect. Since you seem to respond poorly to Rituxan, have you asked your healthcare team about substituting ofatumumab (Arzerra, Humax-CD20) in its place? It should serve the same purpose.
As I said, the track record on ofatumumab is a lot shorter than Rituxan. And no drug is entirely free of adverse effects. But bearing in mind that both R and O are monoclonal antibodies targeting the same CD20 marker, and O is fully humanized monoclonal, it may be reasonable to extrapolate that addition of O might be worth considering.
Harley:
You are not unreasonable in extrapolating these results to PCR – it is very similar to FCR in my opinion. As for the FISH results, I too wish they had provided more detail. The reference to “+12” does indeed mean 12 trisomy. “Complex” and “Other” are catch-all categories for 13q and 17p deletions as well as those patients with more than one FISH abnormality.
warmac9999:
PCO is yet another kissing cousin of FCR, substituting P for F and O for R. Amazing how familiar the alphabet soup becomes after a while. As for completing all 6 cycles or stopping short, that is an excellent question we addressed in an earlier article “How much chemo is too much?”
Brian:
I hope your next move is not something that has to be undertaken right away. At the very least your first transplant seems to have given you a nice long remission.
I think this has been a settled issue among the major players for some time but there is still reasonable debate about how much Rituxan (money) should be used for the desired effect. I think moving to FCO will make this a moot point. Whether to use R or O as maintenance therapy is indeed a good question.
At 1st glance, I was impressed that the FCR group was OLDER than the FC group. This is very rare in CLL when someone has a point to prove. Then I saw the fly in the ointment, the WBC and ALC were almost 2-1 in favor of FCR! 101-61 and 92-51. Having seen so many people progress very slowly over the 100 mark makes me question a little bit. At such a huge center, it is hard to think these were the only 38 cases of FC that they had to make a retrospective study. I would have expected groups withing 10. They are really pushing these numbers with a p value of 0.05 when less than 0.05 would have invalidated the study. I will look later to see how they chose these patients but this is a disease of ALC, not the right place to stack the deck.
The link below is to the abstract of a 2008 paper about life after FCR prepared by some MD Anderson docs and others. The first sentence states:
“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.”
http://abstracts.hematologylibrary.org/cgi/content/abstract/112/11/2090?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=FCR&searchid=1&FIRSTINDEX=0&volume=112&issue=11&resourcetype=HWCIT&eaf
Dr. Hamlin told me that the CR’s referred to in this paper were CR’s under the old ’96 guidelines that are not nearly as accurate as we are getting today with 4 color flow and PCR. I finished FCR 3 years ago this month. When I saw my lymphoma specialist on May 5, he was thrilled with my condition. He has previously told me that he reasonably hopes I never need treatment again (I’m 68). He previously told me that I had gotten an MRD negative CR according to 4 or 6 color flow (He wasn’t sure which).
And I had had a HEAVY tumor burden: 70% marrow involvement and a massive spleen, down into my pelvis and about 6 inches to the right of my navel, with pan cytopenias.
I might add that I had a slightly reduced fludarabine dosage (80% of the recommended dosage, as I recall) and underwent only 4 cycles instead of the usual 6.
Needless to say, I am a big fan of FCR.
Chaya
Thanks for your response. Do you know if an ongoing maintenance treatments of ofatumumab (Arzerra, Humax-CD20) is now generally covered by most health insurances, including Medicare? when i was on rituxan it was “experimental” and not covered by insurance.
Thanks!
Alan
Good information about FCR vs. FC, but what about FR? That is what my doctor is recommending for me soon. I am 13q, mutated, zap70 negative, wbc 44,000, “tiny” lymph nodes, fatigued but not overly. My doctor thinks FCR is too extreme in many cases (even FCR “lite”) and thinks that FR “lite” is more reasonable for early stage CLL. I can’t find any information about FR by itself. Any suggestions?
Dianne
Good luck in your new home; hope you will be happy and thrive! That you are up and going again can only be good for the people you care about, and you do seem to have a big heart.
Be well, Mette
Demeredith, I have similar disease status, but wasn’t even considering treatment for a long time, since it took me 6 years to get to an ALC of 50,000. AS usual, don’t treat the numbers, but more the symptoms.
When were you diagnosed and what is your lymphacyte doubling rate?
Good question, is FR a good choice for smoldering cll?
Next year Rituxan loses its patent protection plus numerous superior anti-CD20 mabs will be hitting the market. Rituxan is expected to drop 80% in price. Keating has based his whole reputation on his FCR studies. The FRC patients in this study were screened and treated at MDA. Where were the FC patients screened and treated? These numbers are small and this is such an individualistic disease. The Binet & Rai staging is rather unfocused; I would like to see a breakdown of the genetic markers in each group. Also the amount of F was less in the FCR protocol. I think it is time to move beyond FC and FCR and I am not yet convinced FCR really extends OS. I predict we will look back some day and wonder why F or C were ever used. If one dies of an infection or secondary cancer long after treatment with F or C is that taken into account in the OS accounting? I am sorry to be such a pessimist.
Chaya, thank you! I hope you are enjoying your new home!
I am very excited to read your report! I am a FCR-Lite graduate and will have my last R maintenance next month. The future does indeed sound promising! I was hoping to be around long enough to see my youngest graduate high school and now it seems I have the chance to be around to see him graduate college! Like Alan in the above post, my immunoglobulin levels were affected. They are still trying to come back up but it has been a slow process. (It has been two years since my chemo ended.)
Thank you for bring us up to date information. You are such an amazing person!
Like a couple other commentors, I’m also interested in any studies comparing FR and FRC. When I was treated back in 2004 it was the consensus among the experts with whom I spoke that the “C” was not adding much (if anything) to make it worth the additional toxicity. Now, however, I understand that views have shifted such that most believe that FRC is the way to go. Has anyone seen any studies on point? By the way, Chaya, welcome to the area. I’m just down the road from you hear in DC.
Thank you, thank you!
Congratulations on accomplishing the move East–hope you will love your new home.
Cheers!
Thanks Chaya!
As CLL patients we are fortunate to live in a time when there are signs of hope that we might have more time than we thought. Meanwhile, it seems the rest of the world thinks they are going to live until they are 96.
As I researcher, I want to say that bad articles read like advertisements and good ones read like a good poem. This one was somewhere in between. With all respect for the leaders who wrote it, and admitting that the improved results with FCR are nothing to shake at, perhaps even offering many of us more years of life with our children and grandchildren, let’s get down to the brass tacks. Azzy notes the low ALC and WBC’s in the FCR group, which is a salient point. There are other biases– for one, the FCR patients were all treated at, yes, MD Anderson, which means many were healthy enough to fly there, perhaps wealthy enough to get a SCT down the road, and tended to have good health insurance and follow up care to fill up the time in between. FC is an older therapy, as I understand, so those who got it did not have the same arsenal of antivirals, DNA monitoring, and other technologies at their disposal. So beware the non-randomized retrospective studies– they are easy to do but difficult to interpret!
I still thank God for FCR and the hope it offers. I would much rather have the option of FCR in today’s world than FC only in yesterdays. We have all read about studies that were discontinued because of poor reactions and reports showing disappointing responses. People are really doing better with FCR. Before the recent reports (esp the German study comparing FR to FCR), my doctor actually said “There is nothing I can give you that will necessarily extend your life.” She changed her position last month (even though she doesn’t offer FCR!) So we will come from Canada, we will march from the chemo-phobic heme-oncs and will descend on those who offer us hope with the triple whammy!
Wow, that is such good news. What a difference a letter makes! As someone who’s only had the FC,does anyone know how long FCR gives as a second throw treatment?
Glad you’re settled Chaya
Molly
ramarx:
You make good points about the difficulties in comparing non-randomized studies. Double arm studies where patients are randomized into two groups are the gold standard of clinical research. Comparing against “historical” norms as this study does leaves room for poorly matched groups and apples versus oranges comparisons. Researcher bias is an unavoidable problem as well, whether or not they are aware of their own bias. Beauty is in the eyes of the beholder.
Unfortunately, it is becoming ever more difficult to do large scale double arm studies. First, they are very expensive. Second, it is hard to recruit for them. Tell me, how many of you would volunteer for a clinical trial if you were told that half of you are going to be randomly assigned to get FC, not FCR? Some researchers argue there is also an ethical problem in assigning patients to a less effective protocol when it is reasonably understood that they can do better on the experimental arm.
Yes, I share your concerns about M. D. Anderson gilding the lily, to some degree. FCR is their “invention”, many of the researchers there built their careers on it. But recent studies elsewhere – such as the excellent German study you refer to – confirm the direction of these results. We reviewed the well conducted and rigorous German study in an earlier article titled “Do patients live longer after FCR?” This was a true double arm randomized study based on more than 800 patients. It left no question that patients treated with FCR did far better than those treated with FC.
I was not an early fan of FCR. But the results coming in from various centers (not just M. D. Anderson) have left little room for doubt any more. For the vast majority of patients, FCR is a better choice than FC. But as always, the devil is in the details. Whether FCR is the right choice for YOU depends on your specific situation.
Hurray to M.D. Anderson and its FCR breakthrough in establishing the golden standard for CLL treatment. Also, shame on local oncologists who failed to give CLL patients the option of treatment at M.D. Anderson, either because they lacked the knowledge of CLL research or were simply satisfied with local standards. Hope that more oncologists will now get aboard with FCR treatment and really save their patients. Most of the lucky CLL patients rely on CLL Topics and or their own web search to get the information they need to make such life saving treatment decisions.
I live in Houston, had RFC in 2005-2006, and I’m still in remission with no side effects or lingering problems. Another CLLer in Houston had RFC in 2001 and, last I heard, she’s still in remission… Most impressive (about 9 years of CLL-free life for her, so far)…
However, I believe RFC’s effectiveness is still tied to prognostic indicators, i.e. it will work quite well with the “vanilla” indicators such as 13q14, mutated, CD38-, CD20+, etc.
We know of patients from the ACOR list who had the non-vanilla indicators and RFC was of limited value to them (i.e. the CLL came back in less than a couple of years)…
We still need to understand what works best for different set of prognostic indicators…
FCR worked for me; what is really annoying is that despite the NICE ruling that FCR is available first line on the NHS and second line if you did not get it first line(yes, this is the UK) some health authorities here are not giving it!
So if you are coming up for treatment ask WHY if you are not getting a monoclonal antibody.
I am aware that patients with co-morbidites are not suitable for FCR; can you get a monoclonal with your chlorambucil? Is there a suitable trial?
If you don’t ask you might not get.
Thank you Chaya,
for this very informative studyresults
But as often in life and statistics, there are no rules without exceptions:
2007/2008 I have had a FCO Therapie within a study.
At the end I had a CR and for a short time a very good life.
End of 2009 I got a 17p Deletion with a very agressive development.
Since then I had contact to some patients with similar bad situation and one Doctor said: The agressiver a therapie the higher the risk of an agressiv genmutation.
Maxi,
Sorry to hear about the turn of events. I am praying for you. You make an excellent point. Each person is an individual. I have noticed a trend in the statistics from extremely respected oncologists (CALGB etc) to treat the people with bad prognosis factors but wait too long to treat the people with good factors (mutated Ig, little cd38,zap70 etc.). Paradoxically, unmutated people survive about 5 years after using the heavy artilery, but mutated people only survive about 3. Did they really wait too long, or were these mutated people in their 80s or more when they finally needed treatment? Of course age adjusted data would help, but which big guy will decide to investigate (and report) whether they have been making bad treatment choices for the last 10 yearS? No one else has access to this data that I am aware of. Another obstacle of the Hipaa laws.
We do need better factors because none of these tell what will happen after stage 2 or who might be at risk to develop gene mutations after treatment. I am sure Ramarx is correct that the wealthy with the option to trot the globe for treatments and obtain the latest drugs with SCT outlive the people who have no health insurance or a battle to get standard care from a local oncologist, but I also know the exception to that rule. There was a very rich man, relatively young. His 1st IgH was over 2, so he was mutated and forced into watch and wait. The next time he came back barely under the wire and used this unmutated call for a SCT. He succumed to TRM in a year and a half.
Thanks for this. I’ll send a copy to our Premier. My email has changed; how do I send you my new one?
Patrick
Maxi:
It is important to remember that statistics talks about large group of people and may not always translate into exactly how an individual may or may not respond. And CLL comes in so many flavors. That is why we must wait for large scale studies to get a good fix on the lay of the land.
I fully agree that FCR is a very potent combination. It is also true that the chances of Richter’s transformation and/or clonal evolution to a more dangerous version of CLL increase during chemotherapy. Please note, the chances increase, but that does not mean everyone who has chemotherapy will automatically have clonal evolution or Richter’s transformation. And clonal evolution can also happen in patient who have yet to be treated.
However, i would like to make one clarification in the logic here. In this article we are not comparing FCR versus a benign, non-mutagenic, non-immune suppressive and non-chemo therapy option. We are comparing FC versus FCR. FC is every bit as likely to cause clonal evolution to a more dangerous form of CLL as FCR
I don’t want people to lose sight of the good news here: addition of Rituxan to FC is associated with significantly improved responses, longer remissions and longer overall survival – all of that without adding significantly to the toxicity associated with FC.
In other words, if the patient’s CLL is at the stage where it requires treatment with potent chemotherapy, and FC is an option for that patient, why not add R to the combo to make it work better? I talk about risks and rewards a great deal on this website. This is how I see it: addition of R to FC significantly increases the rewards without an equivalent increase in the risks. Whatever risks are inherent to FC are already baked into the FCR cake.
Of course, if the patient can make do with lower impact therapy options with matching lower level of toxicity, that is a different ball game.
Thank you for a very informative update I will be passing a copy on to my oncologist whe next I see her
JM
Chaya
It has been along time since I got on the site. Hope everyone is doing well. I had a slight fever two months ago and my HGB went to the floor 4.8 after W&W for 6 years. Of course I never thought it was the CLL thought I was having a heart attack couldn’t catch my breath. Should have studied more! I was told that about 15% of CLL patients develop this hemo-logic (?) anemia. My WBC went from 50 to 278. They kind of stuck me in a hospital in a hurry and I got a few units of blood then we went FCR.
After two sessions so far no side effects and I am at 26K and 14.0 The stuff is great so far.
Each day is a gift.
This is my first posting. My husband, age 50 was d/x with CLL in July of last year. The only negative prognostic indicator he had at the time was IgVH unmutated. Now we are not quite a year into this, and his WBC has doubled (now over 200,000) and his platelets are at 88,000. While he feels well, the above have caused the doctor to now want to pull the trigger on treatment.
A study through Ohio state university would allow him to have either FR or FCR based on randomization. If the bone marrow sample reveals other unfavorable prognostic indicators, he will also have lenalidomide at the end of the 6 months of treatment.
My question/concern is about the FR vs the FCR given his current status. Where is the info about the german study (or any others) that compare these two regimes? Obviously, if FCR is the way he needs to go, we would rather preclude the study and allow him to get everything he needs at this point. However, our doctor seems to feel that the cytoxan may not be totally necessary and may lead to other issues down the road.
We’re scheduled to start on June 21–any info would be helpful! Thanks!!
budgie:
This is a tough call to make and I do not by any means pretend to know what is the optimum therapy for your husband, in terms of FR versus FCR.
That said, cyclophosphamide adds significant fire power to the therapy regimen, unfortunately with a matching increase in toxicity. FCR was pioneered at M. D. Anderson and you will not find an expert there who would recommend anything but, certainly not FR. Ohio State group did the pivotal FR work – mostly from an attempt to see if equally impressive remissions can be obtained without the additional toxicity of “C” in FCR. Since there have been no one-on-one comparisons of these two protocols in a well conducted double arm clinical trial, it is hard to make comparisons.
From what I have seen thus far, and bear in mind the comparisons are not head-to-head and therefore some amount of variability and bias is to be expected, FCR is more potent and more likely to give good remissions in high risk patients. There seems to be some specific advantage of using the “C” along with FR in patients with the 11q (ATM) deletion by FISH.
You did not say what your husband’s FISH status was, just that he was unmutated. But judging from the rapid increase in his WBC and the dropping platelet counts, he seems to have a rather more aggressive form of CLL than you would wish. This is only my two cents as a layperson observer, but if I were in his shoes I would want to get FCR – just to make sure the remission is as deep as possible and holds for a while.
One last thought. If he opts for FCR, it is interesting to note that high doses of cyclophosphamide are tough on the bladder. It really helps if the patient is well hydrated (more glasses of water than he would normally drink!) before, during and after cyclophosphamide infusion and – this is important – the bladder is emptied very frequently so that the drug by-products do not linger there for very long and instead get flushed down the john.
I checked the report from last year, and Larry did not have the 11q deletion or the p53 deletion. It did show a 13q deletion, but the report said that is detectable in about 50% of patients with CLL and usually leads towards a more favorable outcome. It also said no evidence of trisomy 12. The intitial bone marrow did show 70-80% infiltration with leukemia cells. No mention was made at all of 17p, so I assume he does not have that deletion.
Ironically, I had to have cytoxan 12 years ago when I went through breast cancer treatment at age 40. It did indeed irritate my bladder!
The bone marrow will be repeated next week, and from there the chemo decisons will be made. It is the Ohio State study that he is considering. I just didn’t know if there were any other studies/info about FR vs FCR because I did see others here on the forum refer to the FR treatment only. I will keep you posted!
Oh–and I have been giving him around 6 of the Life Extension green tea capsules (2-3X a day) since the initital dx. It hasn’t helped bring the WBC or the nodes down, but he really doesn’t ‘feel’ bad and has had no secondary illnesses at all. Also no night sweats, bruising, weight loss, shortness of breath, etc. etc. If we didn’t know he had this, we couldn’t tell just from looking at him.
I visited Dr. Byrd on a couple of occasions. At my age, 68, he was against the “C” because in his mind biological age correlates with treatment outcomes. I do think that a clinical trial would be better than a straightforward FCR – and Duke has an open PCO trial right now (and all of the patients are experiencing similar and substantive reductions in their white blood count. I was 277 before I started and ended up at 5.2 after the first treatment. Did have some red blood cell impact but now, after 4 treatments, my platelets are at 110 vice 92 prior to treatment.)
By the way, Dr. Byrd did indicate that he would have a trial of some type in the fall, but that is probably too long a wait for you.
Chaya,
NIH mention to me the possibility of FO/FCO treatment. I am having
difficulty finding info on FO., other than:
“Ofatumumab is only FDA approved for use in patients refractory to fludarabine and Campath.”
I have not yet had any treatment.
Any additional thoughts or change from May ’10? Thanks.
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