CSN Login
Members Online: 7

anyone have dense dose chemo and how did it work?

maggie_wilson's picture
maggie_wilson
Posts: 616
Joined: Nov 2009

i've been hearing about dense dose chemo, and am wondering if anyone on this site has had it. if so, what was your experience? did it work better than the usual protocol? i may have missed others posting about this, so sorry if this is redundant.

sisterhood,
maggie

lindaprocopio's picture
lindaprocopio
Posts: 2022
Joined: Oct 2008

I know in dense dose chemo that the taxol is typically given weekly, with other drugs mixed in every 3 weeks for most women. I did do 17 infusions of weekly taxol when I initially recurred, but the dose was at 1/3 strength so that it added up to the same amount of drug as if I'd gotten it once every 3 weeks. So my experience isn't exactly what you are asking about. (I think my weekly chemo was considered 'fractionated', not 'dense dose'.) But I will say that the weekly chemo is easier to take that the big punch of chemo spread out further. The only side effects I had on weekly taxol were baldness and fatigue.

There are several women posting here that were diagnosed in the last year that are on the dense dose carbo/taxol regime. There are also a couple women on the Overian Cancer Discussion Board that are currently getting dense dose, and several who had it. It's an EFFECTIVE chemo; I do see a lot of women getting back to remission on it. I hope you get some better responses to your post than mine.

How is the megace/tamoxifen doing? Has the megace stimulated your appetite? I understand that is one of its side effects, not too bad a side effect IMHO. (((Maggie)))

maggie_wilson's picture
maggie_wilson
Posts: 616
Joined: Nov 2009

i think what you had was different than dense dose, though i wouldn't mind having a fractionated dose weekly than one huge one every three weeks. i have no idea yet what chemo i will be on, frequency and duration until i see the doctor the end of the first week in march (she had to change the time.) in the meantime, i don't think the megace/tamoxifen is doing anything. in fact, i've been steadily losing weight these last few months because of the strict anti-cancer diet i've been on. i've been eating alot, and have a good appetite, but nothing i'm eating is anything that can put on weight. as soon as i know what chemo i'll be on, etc., i'm making an appointment with this great nutritionist who looks at latest labs, cbc panel, chemo i'll be on, etc., and customizes a diet specifically for you. the doctors don't want me losing anymore weight before chemo, nor do i, so i started adding a little dairy, a little meat, what the hell? obviously my great diet didn't stop a recurrence.....

i'll look on the ovarian cancer site as well and see what i can learn about dense dose. i looked it up, and the best that can be said about it is that it made a 2% difference in stopping progression of disease. not exactly a great percentage. this whole dense dose thing is based on this one study, and there have been questions about it, especially by barbara brenner, head of breast cancer action, who i think highly of. so, i don't know. it does make intuitive sense to have a steady stream of chemo rather than bursts of it every few weeks, methinks.

i hope you're doing well on your avastin protocol, and you'll be posting good news to us soon! are you getting ready for your trip to the dominican republic with your son? that sounds wonderful, and i know you'll have a great time together.

i always, always appreciate hearing from you linda, whatever you have to say is always of interest to me.

take care, dear heart.

hugs and sisterhood,

maggie

evertheoptimist
Posts: 140
Joined: Jan 2011

actually, what Linda had the DOSE DENSE PROTOCOL.

The administration of carbo is the same: same dosage as standard every three weeks.

Taxol is given every week, but at a lower dosage. Linda, if you inquire again, you are likely to find out that you were given each more than 1/3 of the regular 3 week dosage.

The regular dosage (once every 3 week) is 180 per body unit (I forget how they compute it). On dose dense, you get 80 each week: so all together in the 3 week period, you are getting more (180 vs. 240).

The idea behind dose dense is to keep the taxol in the body constantly throughout 18 week period, rather than peak and valley of 3 week administration. Dose dense turned out to be a major breakthrough, and they believe it's this constant level that really worked to eliminate the cancer tumors. (in simple words: give the tumor NO break). That's why dose dense works as well as the IP chemo, and a good send for those women who couldn't use IP chemo (like me).

maggie_wilson's picture
maggie_wilson
Posts: 616
Joined: Nov 2009

thanx for your very interesting and informative post. i'm certainly going to discuss it with my doctor, though i'll be having an entirely different chemo combination--yet to be determined. it does make intuitive sense not to give the tumors a rest, however. sounds like you had dose dense chemo or know women who have.

sisterhood,
maggie

evertheoptimist
Posts: 140
Joined: Jan 2011

maggie,

I am on the dose dense regimen. One thing about this protocol. There is NO break. A weekly chemo is a rather intense schedule. There is no margin of error.

If you end up on a schedule like this, you need to stay on top of the Neutrophilis count. Unlike the standard 3 week schedule, if your count is too low they don't delay the chemo, they skip it (unless it's the beginning of the 3 week cycle when they give you taxol and carbo together). When you skip like this, it undoes some of the benefits of this regimen. On the dose dense schedule, it's even more important not to delay or miss the infusion due to the low blood count.

I watch my absolute neutrophilis count (ANC) like a hawk. I get the blood work done on Wed, get the results on Thursday first thing in the morning. If the count is too low, I get an immediate Neupogen shot that same morning, and get the number up enough not to miss the infusion on Friday.

I read enough women talking about missing the infusion because their doctors did not stay on top of the ANC, and they did not advocate for themselves aggressively enough on this important issue. When I was going on a business trip and my ANC was on the borderline, I insisted that they give me the shots so that there is no chance I will miss my infusion when I got back from the trip.

Good luck.

maggie_wilson's picture
maggie_wilson
Posts: 616
Joined: Nov 2009

thank you again for your post. i'm definitely bringing it to my doctor. i'm not sure which chemos they can/will do the dose dense protocol for, so don't know if the assay i had that showed several effective chemo combinations would qualify. nonetheless, it's extremely interesting, and i appreciate you taking the time to report what you are doing.

best of luck to you, as well.

sisterhood, maggie

maggie_wilson's picture
maggie_wilson
Posts: 616
Joined: Nov 2009

i meant to cite where i'd read about the 2% survival rate: it was on Cancer Decisions, december 5th 2010, Cam and Cancer in Israel.

sisterhood,
maggie

evertheoptimist
Posts: 140
Joined: Jan 2011

maggie,

where did you read that the difference between the dose dense and standard was only 2%? I actually read the study, and what I saw was very impressive. In the observation span of 3 years, the mean PFS of the dose dense group was 28 months vs. 17 of the standard group. The statistical significance was through the roof (I am a statistician). I bet, the difference would be even greater if the observation period was longer (beyond 3 years). This is why this study was considered a major breakthrough.

There was also an indication that it worked even better for women with sub optical debulking (like me). So, I was the perfect candidate for this regimen.

lindaprocopio's picture
lindaprocopio
Posts: 2022
Joined: Oct 2008

Ovarian Cancer—New Thinking on Old Regimens
2011 Feb 23, Nelson Teng
Nelson Teng, MD, PhD, is Director of Gynecologic Oncology and Associate Professor of Obstetrics and Gynecology at Stanford University School of Medicine. Dr. Teng is also Program Director for the Stanford/UCSF Gynecologic Oncology Fellowship Program in Stanford, California. For more information, view his profile.

The basis for using intraperitoneal chemotherapy comes from several randomized studies including the now old Gynecologic Oncology Group (GOG) study by Armstrong et al, published in the New England Journal of Medicine in 2006; however, there is a renewed interest in this topic, which has now become an important subject.1

In spite of all of the advances that biologics and newer drugs, the so-called triplet combinations, have made beyond the old standard doublet of carboplatin and paclitaxel as first line therapy, for the most part, either the result is not entirely confirmatory with survival data yet or the drug has shown minimal effect in other solid tumors. Case in point is the findings from the ICON7 trial2 and OCEANS trial which are very encouraging, but we don’t have the final results. It is not clear whether any of the studies of these new regimens will have the same kind of impact on survival of those that I would consider the most important studies published in ovarian cancer in the past decade.

One of those studies is the one I mentioned, which looked at intraperitoneal therapy, and the other one was published by the Japanese Gynecologic Oncology Group (GOG), and looked at dose-dense (not dose intense, e.g. with marrow transplant or stem cell support) chemotherapy in advanced ovarian cancer.3 We can compare these two studies.

In the first study, which is well-known, intraperitoneal vs intravenous cisplatin and paclitaxel were compared. Intraperitoneal therapy showed a tremendously impressive extension of not only the progression-free interval, but also overall survival. The median progression-free survival was increased from 18.3 months to 23.8 months (P = .05) and the median survival difference was 49 months vs 65 months (P = .03), a difference of almost 14 months, which is a whopper in any kind of drug study.

Had this study been not on just a procedure, a technique of intraperitoneal devices, but on a drug of some kind, showing this degree of improvement in survival, it would have been an instantaneous hit and the drug probably would be used even without waiting for completion of an additional confirmatory study. There have been at least three randomized trials that have demonstrated superiority of intraperitoneal over intravenous delivery of platinum-based chemotherapy in patients with optimally debulked advanced ovarian cancer, but intraperitoneal therapy hasn’t really caught on.

There has always been a question in my mind as to why this should be the case. Then, about a year ago, the Japanese GOG reported results from what I consider to be a very well-designed phase III trial showing the benefit of dose-dense, once weekly paclitaxel. When compared with the patients assigned to the conventional regimen of paclitaxel and carboplatin, those on the dose-dense paclitaxel plus carboplatin regimen showed improvement of both the progression-free interval and overall survival. Progression-free survival was 28.0 months and 17.2 months, respectively (hazard ratio [HR] 0.71; 95% CI 0.58–0.88; P = 0.0015). The 3-year overall survival rate was 72.1% vs 65.1% (HR, 0.75; CI, 0.57–0.98; P = 0.03).

A very interesting correlation can be made concerning the possible mechanism of intraperitoneal therapy and also the weekly dosing investigated by the Japanese study. If we consider the reasons that intraperitoneal therapy works, it becomes obvious that it is not simply just the fact that the drug is delivered directly into the abdominal cavity, where most of the ovarian cancers reside. The major mechanism may, perhaps, be a depot, slow release effect by which the intraperitoneal drug, paclitaxel or cisplatin, actually circulates into the blood systemically over time. We know that paclitaxel, when given intraperitoneally, has a very, very long half-life, hence a “dose-dense” effect.

The dosing in the Armstrong study is actually similar to the dose-dense chemotherapy in the Japanese study that was given weekly. Armstrong and colleagues gave 80 mg of paclitaxel per week for 3 weeks. Carboplatin was given at the standard dose, AUC of 6. If we add up the three treatments of paclitaxel, the total dose was 240 mg, which is higher than what we typically use as a pulsed dose of 175 mg. So, by distributing the dose over time, we may have achieved a similar mechanistic effect to that of the intraperitoneal depot effect.

Of course, one of the issues here is that hematologic toxicity is frequently dose-limiting. Hematologic toxicity, particularly thrombocytopenia, is carboplatin-related. Somehow, with intraperitoneal delivery or dose-dense therapy, we can actually reduce the incidence of this toxicity.

Another issue is higher hematologic toxicity with intravenous chemotherapy than with intraperitoneal chemotherapy. The real question is whether we are able to use these two studies to advance the field by looking at a different regimen, as well as a more convenient way of administering therapy instead of intraperitoneally, by actually using intravenous therapy.

Currently, GOG is conducting a trial, GOG 252, in which they compare the different intraperitoneal dose-dense regimens and, then, just to do the fashionable thing, will add bevacizumab to all of the regimens, which will be followed by bevacizumab maintenance therapy. It does not directly compare intraperitoneal and intravenous delivery; nevertheless, we may get a useful result. In short, there is a significant contribution to be made by really looking at the therapy that we already have on hand. For example, in pediatric acute lymphoblastic leukemia, significant improvement in survival was achieved in the past several decades without the introduction of any new drugs.

There are several things to consider in these two studies. One common criticism of both studies is the high dropout rate. Of interest, both studies have very similar dropout rates. In fact, in the intraperitoneal study, only 42% of patients received all six cycles of chemotherapy and in the experimental arm of the Japanese study, 48% received all six cycles. However, if all the patients had completed the six-cycle treatment in either of these two studies, the result would have been even more dramatic. The high noncompletion rate was caused, mainly, by severe hematologic and neurologic toxicity, pain, and fatigue.

Another criticism is that the Japanese population might be different from others, so there may be ethnic or racial differences. For example, there is a difference in histologic distribution of tumors, with higher incidence of clear cell carcinoma in the Asian population; clear cell carcinoma carries a poorer prognosis. However, when the Japanese analyzed only the serous papillary tumors, they still observed an improvement in survival. In fact, in their study, using the dose-dense schedule did not show an obvious impact on outcomes in patients with clear cell carcinoma.

There are other differences in the inclusion criteria, such as the inclusion of stage II disease in the dose-dense trial, whereas, only stage III patients were studied in the intraperitoneal trial. There might also be variation in the surgical debulking techniques used. The GOG 252 trial probably will be one of the studies in which these questions can be answered.

There are other intriguing mechanisms involved. For example, paclitaxel, given at a low dose may have, in itself, an anti-angiogenesis effect, which may be synergistic with the chemotherapy regimen, especially when paclitaxel is given in a dose-dense manner. One wonders if this would explain why in the phase III GOG 218 trial, which looked at bevacizumab in women with advanced ovarian cancer, an improvement in progression-free survival was only observed in patients who received continued bevacizumab maintenance therapy. Women treated with carboplatin and paclitaxel, with or without bevacizumab, showed no difference in progression-free survival.4 The anti-angiogenesis effect may already be maximized by paclitaxel, such that the addition of bevacizumab to chemotherapy showed no significant improvement.

By better dosing, which could be a lower dose of both carboplatin and paclitaxel, the hematologic and other toxicities can be reduced. The kinetics may be more similar to that of the traditional low dose, continuous metronomic chemotherapy. Although the verdict is still out on whether these traditional therapies should be pushed aside in favor of biologics, consideration must be given to the side effects of the newer agents, especially longer term and also a serious issue relative to cost.

These two seemingly very different types of regimen may share a common mechanistic fundamental. The result of one study actually affirmed the other. There were two different methodologies, evaluated in very different patient populations, yet showing comparable superior survival curves. Further investigation of the old drugs with innovative dosing and scheduling, and also delivery, may be in order.

References

1. Armstrong DK,, Bundy B, Wenzel L, et al. Intraperitoneal Cisplatin and Paclitaxel in Ovarian Cancer. N Engl J Med.2006;354:34-43.

2. ICON7. A phase III randomised Gynaecologic Cancer InterGroup trial of concurrent bevacizumab and chemotherapy followed by maintenance bevacizumab, versus chemotherapy alone in women with newly diagnosed epithelial ovarian (EOC), primary peritoneal (PPC) or fallopian tube cancer (FTC). Paper presented at: 35th European Society for Medical Oncology (ESMO) Congress; October 8-12, 2010; Milan, Italy. Perren T, UK, Presenter. Abstract LBA4.

3. Katsumata N , Yasuda M ,Takahashi F, et al. Dose-dense paclitaxel once a week in combination with carboplatin every 3 weeks for advanced ovarian cancer: a phase 3, open-label, randomised controlled trial. The Lancet. October 2009 374(9698):1331-8.

4. Burger RA, Brady MF, Bookman MA, et al. Safety and subgroup efficacy analyses in GOG218, a phase III trial of bevacizumab (BEV) in the primary treatment of advanced epithelial ovarian cancer (EOC), primary peritoneal cancer (PPC) or fallopian tube cancer (FTC): a Gynecologic Oncology Group study. Paper presented at: 35th European Society for Medical Oncology (ESMO) Congress; October 8-12, 2010; Milan, Italy. Proffered Paper 978.4.

maggie_wilson's picture
maggie_wilson
Posts: 616
Joined: Nov 2009

i'm printing your post and bringing it to my doctor, as well as evertheoptomist's post. both are extremely intriguing and hopeful. i'm so glad you are on this, linda, and bring us the latest information. so much food for thought. it certainly makes sense that innovative ways of delivering chemo as well as new drugs, have the most promise. sounds like we're going to have to be, as always, strong advocates for ourselves. then there's the question of insurance, and which procedures they will cover, and which they will not. it's always a question with insurance. nonetheless, i feel much more armed with information as i anticipate my next doctor's appointment.

thank you again, linda. what a gem you are. hope you're still feeling good, and will have good news to report. in the meantime, i'm so glad you're tolerating your regimen so well. i feel armed, as i said, but also inundated with new information, which brings me ultimately back to the crap shoot theory of treatment. one never knows how one will tolerate even the best chemo or procedures available.

in the meantime,

hoping for the best for you, as always. and lots of hugs.

sisterhood,
maggie

evertheoptimist
Posts: 140
Joined: Jan 2011

linda

thanks for posting this article. Very much appreciated. This is very consistent with what I researched, that is, dose dense is a god send for women like me for whom IP was not an option (I had suboptimal debulking) and evened playing field, sort of.....

All these findings are making me "realistically" optimisitc and escape from the curse of published statistics. On the paper, my diagnosis (UPSC 4B) would have an awful prognosis, but the data that went into that statistics do not reflect the breakthroughs options and treatment modalities that are just being deployed.

I am very lucky that I have an gyn oncologist (also my surgeon) who was on top of the latest development. He also put me on Avastin (again, supposedly more effective for suboptimally debulked patients vs. optimally debulked ones).

california_artist's picture
california_artist
Posts: 860
Joined: Jan 2009

In the book Anti Cancer... he has pictures of what happens to cancer progression in what he refers to as metromic chemo vs. conventional chemo. It has always made sense to me that just as an antibiotic needs to maintain a certain level in the body to keep the disease from becomiing resistant, that cancer should also have a steady delivery of drugs or some other remedy, to combat it.

Mary Ann has said that she is inspired by your posts and reasoning, would love if you would email or call me to throw some ideas around.

Thanks for your level of sharing,

Claudia

claudiaallen27@yahoo.com please mention UPSC in the subject line. I delete most posts.

906 863-1732 I'm on central standard time.

February 27 will be three years since I was found to have cancer. UPSC. No chemo or radiation. Just an assesment of what causes cancer, what helps cancer to survie or what cancer needs to live, and then a very careful program designed to not do those things and to do what I can to further slow the progression. I'm hangin in there. Although in the beginning when everyone was getting therapy and I was doing things like eating grapes first thing in the morning, maintaining an alkaline diet,eating ginger and drinking green tea, using the turmeric, black pepper and olive oil concoction, I had some severe twinges of wondering if I was doing the right thing or not.

I don't know anything of your story. But if Mary Ann thinks you're swell, you're okay by me.
Look into Dr. Boik if you haven't already. He is all about natural therapies and statistics. He was at Stanford, not sure where he is now. But if you find him replys to emails post haste.

evertheoptimist
Posts: 140
Joined: Jan 2011

I don't know your diagnosis or whether you had a surgery or not, so I can't comment on your treatment options.

I read all the books you mentioned and more. As for me, I would never consider not doing the conventional therapy (chemo). My condition was acute and it required a major intervention. I also firmly believe in integrative oncology to maximize the odds of good prognosis going forward.

The combination of conventional medicine and integrative medicine will give me the best odds I can have.

However, I believe the single most important thing I have that will let me emerge on the extreme far right side of the statistical curve is my mind - the discipline to do everything within my power, the will to survive, and the rationally grounded positive outlook on life. The other day, I was skyping with my son in college, and I was talking about how cancer took away certain things but how many precious gifts it sent in my way, and he said "mom, you are making me feel cheated for not having a cancer of my own". I believe even a life's crisis can be salvaged for the beauty it brings, and you need to look at unconventional places to find this beauty.

california_artist's picture
california_artist
Posts: 860
Joined: Jan 2009

The book that mentions metronomic therapy for chemo is Foods That Fight Cancer. It's lovely and inspiring.

I am in total agreement that a positive, can do anything, just get out of my way attitude can do wonders for a positive outcome.

Subscribe with RSS
About Cancer Society

The content on this site is for informational purposes only. It is not a substitute for professional medical advice. Do not use this information to diagnose or treat a health problem or disease without consulting with a qualified healthcare provider. Please consult your healthcare provider with any questions or concerns you may have regarding your condition. Use of this online service is subject to the disclaimer and the terms and conditions.

Copyright 2000-2014 © Cancer Survivors Network