I thought that since this will be my last post as the Ovarian Cancer guide, I'd briefly reflect on the past year and give some encouragement about the future. As we enter 2009, there is much hope for new screening tools, biologicals are coming of age and it won't be long before they overtake toxic chemotherapy. Into the intermediate future, we are looking at genetic therapy, both pre-birth and influencing epi-genetics via medical and dietary interventions. There is reason to be VERY optimistic.

We have covered a lot of this during the past year, and I had hoped to continue along the same vein of presenting today's sometimes harsh treatment reality choices, look towards the better and brighter future and fill in with complementary and alternative approaches that seem to have some promise, proven or not. But that is not meant to be.

Our forum has grown from zero to very active in a very few short months, and I hope you have found a good "home" for healthy discussion regarding experiences, good and bad. I tried to pop in and say hello often, and if I have not caught everyone, a warm welcome to a safe discussion zone for the moment. I think the site may serve you well for that, although I have no idea who will be recruited to answer the medical questions. About is usually pretty good about seeking out good folks, so I hope for the best.

Overall, it has been an honor serving your information needs, hearing from you individually and recommending what I would consider as options. You are true survivors and for the newbies on the block, listen and you shall find iron wills and very strong support from those that have been there, done that.....right here in this forum.

I bid you farewell. In case you need to find me, I can't really put in an email address here for conflict of interest reasons, but if you Google me, I am not hard to find. I anticipate a much bigger presence on the web and hope to see you around. Live long and keep your eye on the prize.

Kind Regards,
Dr.Steve

We've gone round and round on the relative major inaccuracies of CA-125 blood tests to detect ovarian cancer. There are a number of research avenues that are being investigated to improve early detection, and this is one of them.

Researchers at the University of South Florida have just reported their results on a protein, called Bcl-2, which can be picked up by a urine test. Bcl-2 is something called an "anti-apoptotic" protein, which can be found in many cancers, but they investigated it by testing healthy women, women with benign non-cancerous gynecologic conditions, and in women with early or advanced ovarian cancer. In many cases, they compared the result with a CA-125 blood test level.

Women who had been diagnosed with ovarian cancer, regardless of stage, had a significantly elevated level of Bcl-2 in the urine compared to women who had either no disease or benign conditions. Furthermore, the levels roughly correlated with CA-125 elevation. Is this THE answer? Probably not....or at least not the only answer. However, it is a step in the right direction towards effective screening.

Although this is early laboratory research, it caught my interest. We know that one of the most useful drugs for ovarian cancer treatment has been cisplatin. The way the tumor responds to this drug will often define the prognosis.

Initially, most patients do respond to this chemotherapy for their ovarian cancer. Eventually the majority of the ovarian cancers become resistant to the cisplatin. This lab study could give some hope. If the power of cisplatin can be improved by this method, it would have a major impact in the fight against ovarian cancer.

The drug I'm alluding to is called Arsenite (arsenic trioxide). It begins by working to attack the ovarian cancer cells but also works by using multiple biological processes to enhance the effectiveness of cisplatin to inhibit DNA repair. There have been some in-vitro studies (in the lab) that show Arsenite can enhance the activity of cisplatin in other cell types as well.

If some of you recognized the word "arsenic" in this compound, yes it is the same thing as the drug we have all just considered a poison in the past. However, Arsenite has been used to treat some types of leukemias for some time now, which shows it can be used safely. Granted this seems odd, but not the first time a "poison" has been used towards a good cause. Watch for upcoming clinical research in this area.

Researchers at the University of Hawaii have been tracking the incidence of papillary serous Primary Peritoneal cancer. We have known about this “uncommon” malignancy for about 5 decades, and now it may be on the rise.

In the USA, this is generally a disease of older white women, usually not seen under the age of 40. However, it is also diagnosed in other ethnic groups. The majority (68%) is diagnosed at an advanced stage.

This research group tracked the incidence of primary peritoneal cancer in the US from 1995-2004. Unfortunately, they found that there is a dramatic increase with the greatest rise (>13% per year) among non-Hispanic and white women. Reasons are unknown at this time, and some of this may be due to how ovarian cancer was classified in this set of databases.

So what does this mean? Well, hopefully some of it is related to the last reason, which is essentially how things are recorded rather than real increases. However, it may also be a disturbing trend, adding to our already poor sensitivity for ovarian cancer screening. Over the next few years, the blood tests that are being developed for ovarian cancer screening will help find this disease. On the other hand, primary peritoneal cancer usually means that many areas of the peritoneum have gone bad. Because of this, an “early diagnosis” is uncommon.

Just released information from Dr. Michael F. Leitzmann of the National Cancer Institute strongly ties obesity to development of ovarian cancer. This study looked at 94,525 U.S. women aged 50 to 71 years over a period of seven years. 303 ovarian cancer cases were found during this time. Among women who had never taken hormones after menopause, obesity was associated with an almost 80 percent higher risk of ovarian cancer.

What this means is that obesity may increase the risk of ovarian cancer through hormonal effects. Body fat cells produce estrogen, so the more you have, the more estrogen gets produced. Even though this type of estrogen is weaker than that produced by ovaries, it can apparently still cause adverse events....like ovarian cancer.

So, this might be an excellent time to re-double efforts on the weight loss program that your New Year's resolutions included.

The PET scan for ovarian cancer, in my opinion, is a misunderstood test. Because of it's expense and "lack of data" and lack of approval leads payers to deny coverage often. Why is that? It's just a test. It will not lead to someone living longer by itself, just like CT or MRI scans and CA125 or other tumor markers. But if you take that position, may as well not pay for anything. Any test or procedure in the care of ovarian cancer, or any medical condition, can be misapplied.

With regard to the role of PET scanning in ovarian carcinoma, it appears to be particularly useful for the diagnosis of recurrence when CA125 levels are rising and conventional imaging is inconclusive or negative. Is this always helpful additional information? No! If the plan is not going to change much, for example chemo vs. no chemo, then finding the details of where the cancer might be located is not too helpful. That may only shift the date of chemo by weeks or months, without helping you live any longer. On the other hand, if the location of disease and number of areas involved will help make the decision of surgery vs. no surgery, then it can be crucial. There is no point in operating with suboptimal information only to find out during surgery that the surgical plan was a bad idea (e.g. "cancer all over the place and not removable"). The point is that deciding whether or not to perform a test, including the PET, is a multifactorial rather than a knee-jerk decision. In the right decision-making "hands", proper selection of testing can make the difference between avoiding unnecessary surgery (or not) and sometimes the difference between life and death.

From a purely technical standpoint the data is growing and the role of fluoro-D-deoxyglucose (FDG)-PET along with CT for the detection of recurrent ovarian cancer appears very promising. This a test which melds detection of abnormal anatomy and physiology very well. The devil is in the decision details as to when to use what and, more importantly, what difference it can make. If denied, go over these details with your trusted physician.

Perusing the latest from several sources.... I thought I'd post a list of biotech meds in development at various stages of clinical trials as of December 2008. Some are specific to ovarian cancer, others are being tested in several areas, and some include Fallopian tube and primary peritoneal cancers which are certainly treated in a very similar way. After the listing are phone numbers you can call for more info, where available.

AMG386 from Amgen is a recombinant fusion protein in Phase II (805)447-1000

Avastin from Genetech is a monoclonal Ab in Phase III (650)225-1000

DCVax-L from Northwest Bio is a dendritic cell vaccine in Phase I/II (240)497-9024

EGEN-001 from Expression Genetics is an interleukin in Phase I (256)512-0077

Herceptin from Genentech is a monclonal antibody in Phase II (650)225-1000

IL-21 from Zymogenetics is an interleukin in Phase I/II (206)442-6600

IMT-1012 from Immunotrope is an immunotherapeutic vaccine in Phase I (215)253-4180

Advexin from Introgen Therapeutics is in the gene therapy arena Phase I (512)708-9310

Neuvenge from Dendreon is a dendritic cell vaccine in Phase I (206) 256-4545

OmniTarg from Genentech is a monoclonal antibody going to Phase III (650) 225-1000

OvaRex from ViRexx is a monoclonal antibody in Phase III (780) 433-4411

Ovax from AVAX is a vaccine in Phase I/II (215) 241-9760

Tucotuzumab celmoleukin from EMD Lexigen is a fusion protein in Phase II (978) 294-1100

volociximab from PDL BioPharma is a monoclonal antibody in Phase II (510) 574-1400

There are others and I will post on those from time to time as they come across my research desk.

An article buried on the 29th page of the December AARP Bulletin caught my eye today. The topic is Kathy Adams, a 49 year old breast cancer survivor who it trying to serve our country in the US Foreign Service. She has passed the written and oral examinations, but then there is the breast cancer thing. She had undergone mastectomy and is apparently free of disease. However, due to inability to accommodate followup needs, according to the article, she is being denied this position which she otherwise apparently qualifies for.

Now, I may be missing something, or the story may be incomplete, but this is not the only story I have seen like this. There are a lot of intentional and unintentional discriminatory stories surrounding cancer survivors. The litigation is ongoing, and without getting on a soapbox, I thought this was an opportunity for an objective statement regarding your rights as a survivor.

If you feel that you have been dealt with unfairly in trying to obtain a job, or were let go, because you have cancer as a "disability", you should investigate the internal appeals process for that opportunity. If it is too late for that, you are free to contact the US Equal Opportunity Commission and see what your rights are. You can find them at www.eeoc.gov

A recent e-publication from New York, from Dr.Nezhat and company, sparked my interest for a commentary. Dr.Nezhat and colleagues, who are known for minimally invasive surgery, have restated what may be the obvious in this day and age.

The group reviewed 36 patients over a 12 year period (1995-2007), noting that it was feasible to perform the usual staging procedures laparoscopically in early cancers, including lymph node sampling, peritoneal biopsies and removal of part of the omentum. The complication rate was moderate, but not life threatening and, the most important factor, 7 of the 36 were upstaged. This means disease was found outside of the ovary and lifesaving treatment added, although three have suffered a recurrence as of the publication date.

The conclusion of the study is that laparoscopic surgery in this situation is effective and does not compromise survival, as long as it is performed by an experienced gynecologic oncologist who is expert in minimally invasive surgery. Although seemingly small, this is one of the larger studies which have long-term follow-up.

I would comment that, although some randomized studies are still underway, we have enough cumulative experience to say that minimally invasive surgery should be considered as today's standard.....or at least offered as an option in many, if not all, cases. Of course there would be dissenting opinions. However, most of those would be from those who do not perform laparoscopy in their oncologic practice.

My personal use of laparoscopy in these situations dates back to the 80's, much of which went unpublished, and many of my colleagues also have reams of unpublished experience. Laparoscopy is simply an instrument, a tool, and in the right hands is quite effective. The upside is what we all know.....MUCH faster recovery. The downside? Not much, although each patient's situation is different. Regardless, it is something to discuss with your physician in the event you are suspected to have early ovarian cancer.

As usual, comments welcomed and encouraged....

It has been known for a while that research and treatment of breast cancer has advanced at least partly because the disease is sub-classified by a number of factors from histology to hormonal and molecular marker status. Is this the case in ovarian cancer?

While ovarian cancer is broadly sub-classified, mostly on histologic basis (i.e. what it looks like under the microscope), treatment for everything but low malignant potential tumors (LMP or borderline) has been largely stuck in the Taxol/Platinum paradigm. So, most women who develop ovarian cancer will be offered these two drugs at first, assuming they do not enroll in a clinical trial. This may be suboptimal because there is increasing reason to believe that ovarian cancer is a group of diseases, not just one.

As an example, one publication hot off the presses from Canada suggests that subclassification of ovarian cancer can be better used to guide treatment and determine prognosis BMC Cancer. 2008; 8: 17. Specifically, they are talking not only about histology (i.e. serous or clear cell etc.) but also about molecular events such as the mechanisms behind BRCA1 and 2 alterations as well as p53 and other pathways. This is a developing theme in research circles, since it is becoming clear that cancer is even more complex than initially thought with literally thousands if not millions of molecular pathways intertwined. However, it is not readily appreciated by clinicians and clinical researchers that we have to sub-classify ovarian cancer patients better and enroll far more in well-designed clinical trials to find "the answer"....which will undoubtedly be a complex solution as it is.

As it stands, even when patients are enrolled in chemotherapy clinical trials, most trials will accept a fairly broad range of ovarian cancer types, which means the results of the trial may not be as pure as they could be. Especially as we move towards molecular therapy, this will have to change.