Ovarian Cancer: Something Old, Something New

 


I do hope that you and yours had a very happy holiday.  I want to wish you health, happiness and success for the New Year.


 


I apologize to those who wonder where I may have been the past several weeks.  I took some much needed time off from work, with every intention of continuing to post the blog occasionally during the interval.  As situations dictated, I had to really take some time off for various reasons, so the computer remained closed for the duration.  But, we are back, and hopefully that won’t happen again—at least not until next December!


 


Now, back to the blog:



 


 


There is an article and editorial released for publication this afternoon in the New England Journal of Medicine about the use of intraperitoneal chemotherapy (giving chemotherapy drugs directly into the abdomen through a small tube, or catheter) in the treatment of advanced ovarian cancer.  They are accompanied by a press release from the National Cancer Institute, and I suspect this will get a fair amount of media coverage.


 


The article interests me for a couple of reasons:


 


First, the therapy isn’t really new.  Second, the news release suggests that this is now the standard of care, despite many of the problems with the treatment that have still not been addressed.


 


Those issues do not, however, cloud the fact that the study is significant and that the survivals are considerably better than what has been seen before in the treatment of women with this stage of disease.


 


Let’s examine for a moment why the issue is so important.


 


Ovarian cancer is not rare, but it is not common.  In 2005, the American Cancer Society estimates that 22,220 women will be diagnosed with ovarian cancer, while 16,210 women will die from the disease. In fact, over the period from 1975 through 2002 (the latest year for which statistics are available), the rate of ovarian cancer has actually been decreasing about 0.5% each year (that means for every 100,000 women, there were about 14% fewer cases of ovarian cancer in 2002 than would have been expected compared to the rate of the disease that occurred in 1975).


 


The reason ovarian cancer is of so much concern is that it is the fourth most common cause of cancer death in women (6% of cancer deaths), and strikes many of those women well before their 65th birthdays.  It is also a silent disease: symptoms leading to diagnosis are almost always associated with advanced ovarian cancer.  Unfortunately, there are no reliable screening tests that can be recommended for women who are at average risk of the disease.  The net result is that very few women are diagnosed with ovarian cancer when it remains confined to the ovary and has the greatest opportunity to be cured by surgery.


 


When ovarian cancer spreads, it usually stays within the abdomen and doesn’t spread widely like so many other cancers.  As a result, doctors for many decades have focused their treatment efforts on how to attack this cancer in the abdomen.


 


Years ago, there were some attempts at treating the whole abdomen with radiation therapy, but lack of success and significant side effects resulted in the abandonment of this approach (doctors used both what we call external beam radiation therapy and injections of radioactive isotopes into the abdomen during that era.  The result was not much success and a lot a scarring in the abdomen which in turn led to blockages of the bowel among other side effects).


 


As we developed cancer drugs which seemed to have some greater benefit in treating ovarian cancer beyond the initial oral drugs we used in the 1960s and 1970s, some experts thought that it would be better to give the drugs directly into the abdomen instead of intravenously through a needle.


 


Simultaneous with this, doctors began to aggressively remove the cancer that developed in the abdomen through an operation called “debulking.”  The goal of these surgeries was to surgically remove as much cancer as possible and leave behind the smallest amount of cancer, in the event it could not be completely resected.


 


With the new chemotherapy and the more aggressive surgeries, doctors were hopeful that we could effectively treat this cancer.  There was even a routine recommendation for many of these patients that they have second-look surgeries to check on the response of the treatment.


 


All of this occurred many years ago.  There was improvement in the treatment of women with ovarian cancer, but not as much as had been hoped for.  The idea of giving chemotherapy directly into the abdomen (called intraperitoneal chemotherapy) more or less fell by the wayside.  We never did develop chemotherapy drugs that were able to cure ovarian cancer.


 


The current study resurrects the intraperitoneal treatment, combines it with more standard intravenous chemotherapy, and compares it to a treatment that uses only chemoterhapy drugs given intravenously.


 


The researchers report that there were significant improvements in two measures of treatment success where the combined intraperitoneal/intravenous approach was compared to the standard IV treatment: the time it takes from when the therapy starts until the disease starts to progress, and overall survival from the cancer.


 


For the first measure, for the women who had the combined therapy, the median time to progression was 23.8 months from the time they started the treatment compared to the women on the standard IV drugs who took a median of 18.3 months (“median” means one half of the women progressed before the time noted, while the other half took longer).  The difference in the medians is about 5 ½ months.


 


The improvement in the second measure of the study, survival from the start of treatment, was even more dramatic.  These numbers were 65.6 and 49.7 months, respectively, for the median survival.  This difference is about 16 months.


 


That’s the good news.  The bad news is that the treatment with the medicines injected into the abdomen did not come without a significant personal cost.  The women who received the combined treatment had a much worse quality of life while they were receiving the treatment.  Fortunately, this got much better over the next year and by that time both groups had about the same quality of life.


 


This probably was due to some of the severe side effects of the combined treatment.  Those women had severe abdominal pain, fatigue, and other side effects.  Only about 4 out of the 10 women who were supposed to receive the treatment into the abdomen were able to complete their entire course.  Almost half of the women received 3 or fewer of the planned abdominal treatments.


 


Despite the fact that completion of the treatment was so difficult, the results were still significant.  What this means to me is that if we are able to find ways to deal with some of the side effects of the treatment, and help women get through the entire treatment course, the results may be even more dramatic than those reported.  (Perhaps an explanation would be helpful.  See * below if interested.)


 


So what does this mean? 


 


First, even old, discarded treatment approaches may have some value when reexamined in the light of current knowledge (see the previous blog entry on vitamin C as an example of how new thinking can revive interest in something that has been previously tried and thought not to be effective).  Second, we still have much work to do to make this treatment even more effective, such as finding better ways to overcome the significant side effects of the treatment, and improve the catheters we need to inject the drug into the abdomen.  Third, we need to overcome biases among many physicians that intraperitoneal chemotherapy doesn’t work.  This study suggests that it does, and we have to train more doctors to give the treatment.  Finally, we need to continue the clinical trials to figure out the right drugs to use in this approach to get the maximum benefit.


 


I agree with the doctor who wrote the editorial in the same edition of the Journal that we are going to have to figure out how to get this treatment to the women who need it.  We need to train the doctors to do it, and we need to figure out ways to give this in community hospitals and cancer centers. We need to have extremely supportive and knowledgeable nurses, especially since the pain and fatigue of this treatment are so substantial.  And for women who don’t have access to this treatment in their home towns, we need to find ways to get them to centers that do have the capability to treat them.


 


But, with all the interest and possible excitement that this research may generate, we must not lose sight of the fact that we need to find better tools to discover ovarian cancer at its earliest stage, when there is a much better chance for a real cure.  That would represent the best progress against this very insidious and deadly disease.


 


 


 


 


* When we report clinical trials, we usually do so on what is called an “intent to treat” basis.  That means that once assigned to a treatment group, even if you don’t complete the treatment, you are still counted as part of that group.  This hopefully gives us a better understanding of what the true impact of the treatment is, as opposed to counting only those who complete an entire course of treatment which could make the treatment look better than it really is.  In this particular study, the practical implication is that even though only about half of the women got the full course of treatment, the results for those women were so much better than the standard treatment that it made the results better for the entire “combined treatment” group—even those who didn’t complete the whole course of therapy.  I suspect that if all of the women were able to complete the treatment, there would have been even greater success for the combined treatment group.


 

7 thoughts on “Ovarian Cancer: Something Old, Something New

  1. In reply to the Gynaecological Oncology Group study that had been reported in the January 5th edition of The New England Journal of Medicine, it could be an indication of the “Right Therapy” but the “Wrong Drugs.”

    The hallmark of cancer is heterogeneity. Not just many types of cancer, but many subtypes of cancer within a given type. The biologies are very different and the response to given drugs is very different.

    The hallmark of cancer treatment is heterogeneity. There are currently over 100 FDA approved cancer drugs, with hundreds more in the pipeline. All of these drugs tend to be partially effective, and even then, in only a minority of cases, and often for only a short duration of time.

    The single most neglected area of cancer research has been the development of methods and technologies to be “matchmakers” between individual cancer with individual cancer treatment.

    The single most neglected area of cancer treatment has been the unwillingness to utilize the matchmaker technologies which have already been developed and available. These technologies involve studies of cancer cell responses to drug exposure in cell culture systems, “outside” of the patient’s body, before they are put “into” the patient’s body.

    With only 42% of the women being able to finished the rather arduous trial, perhaps abdominal chemo is the right therapy, but they were using the wrong drugs? Test the tumor first!

  2. The concept of testing cancer cells in culture, much along the lines of what we do for infectious diseases, has been studied for a number of years. I haven’t looked into the process recently, but my sense is that it hasn’t caught on in the oncology community, perhaps for many of the same reasons that intraperitoneal chemotherapy fell out of favor only to be “resurrected” by the NEJM article.

    One of the clear goals for the future is to match patients and drugs, along the lines of the recent advances in the area of targeted therapies for lung cancer. There are, as you may be aware, many other efforts to be certain that the right patients are treated for the right reasons with the right drugs. There is much yet to be learned, but it is clearly a goal of much research that is currently ongoing.

  3. Reimbursements Sway Oncologists’ Drug Choices

    A joint Michigan/Harvard study confirms medical oncologists choose cancer chemotherapy based on how much money the chemotherapy earns the medical oncologist.

    Just published in the journal Health Affairs is a joint Harvard/Michigan study entitled “Does reimbursement influence chemotherapy treatment for cancer patients?” In a study of 9,357 patients, the authors documented a clear association between reimbursement to the oncologists for the chemotherapy of breast, lung, and colorectal cancer and the regimens which the oncologists selected for the patients. In other words, oncologists tended to base their treatment decisions on which regimen provided the greatest financial remuneration to the oncologist (Jacobson, M.,O’Malley, A.J., Earle, C.C., et al. Health Affairs 25(2):437-443, 2006).

    This study adds to the ‘smoking gun’ study of Dr. Neil Love on the subject. The results of his survey show that for first line chemotherapy of metastatic breast cancer, 84-88% of the academic center-based oncologists prescribed an oral dose drug (capecitabine), while only 13% prescribed infusion drugs, and none of them prescribed the expensive, highly remunerative drug docetaxel.

    In contrast, among the community-based oncologists, only 18% prescribed the oral dose drug (capecitabine), while 75% prescribed infusion drugs, and 29% prescribed the expensive, highly remunerative drug docetaxel. The existence of this profit motive in drug selection has been one of the major factors working against the individualization of cancer chemotherapy based on testing the cancer biology.

    Once a decision to give chemo is taken, physicians receiving more-generous Medicare reimbursements used more-costly treatment regimens.

    Two scientific “evidence-based” studies with a dose of reality (pun intended).

  4. Hi!! Been looking for Ovarian-cancer-treatment for a week, 10hours a day,I was treated for prostate-cancer in 1999,radiation-seeds-hormone & radiation treatment ! My understanding is that Hormone-treatment,- “blocks” cancer-cells from developing ! If so,- the comb. of Chemo & hormones,- can that be effective after Stage 3 surgery , with the lymphnodes removed as well ???My ex. had it last thursday !!After 3 years of bleeding,where as Ultra-sound was never used,such not detected earlier !!
    Sincerely

    Svein Kobbeltvedt

  5. Check out the pictures of beautiful, bald women from the book, “TURNING HEADS: Portraits of Grace, Inspiration, And Possibilities” at:

    http://tinyurl.com/l9enb

    TURNING HEADS contains pictures of women who have lost their hair due to chemotherapy. It features some of the best fashion and news photographers in the world — including four Pulitzer Prize winners.

    Many women diagnosed with cancer fear losing their hair more than losing their lives. This fear can prevent them from getting proper treatment.

    Filmaker and cancer survivor Jackson Hunsicker spent five years assembling these inspiring images. “The women in these pictures are out in the world, doing things, getting on with their lives while they recover,” says Hunsicker. “They teach us all a much needed lesson that bald is a look you can live with.”

  6. An ovarian cancer stage depends on how far the tumor or disease has spread from the pelvic area, if it has at all. If it hasn’t, chances are good the ovaries can be removed and a woman will be fine.

  7. I was diagnosed with stage IIIc ovarian cancer 1/07. I had optimal debulking by an oncologic surgeon 1/22, started chemo 6 weeks later. I had IV and IP taxol and IP cisplatin. The treatment was pretty awful but I was able to take all treatments at 3 week intervals. I did not have to take any breaks in the treatment and I finished in 4 1/2 months. My question is regarding the study. I am best case scenario. I cannot find any information about the rate/timing of recurrence or survival among those who received treatment just as the study proposed. Were there any? I’d like some better info for figuring my chances. Is anybody gathering information now about the success of this treatment now that it is being used fairly widely? The drugs I waw given for side effects were effective for me. Surely lots more women are now able to complete the treatment, even if not precisely on schedule. Does anyone know who I could contact?

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