www.patientpower.info sccapatientpower.org SCCA052108/0606/AS/jf © 2008 Seattle Cancer Care Alliance All Rights Reserved 1 The Latest in Gynecological Cancers Webcast May 21, 2008 Banjamin Greer, M.D. Please remember the opinions expressed on Patient Power are not necessarily the views of Seattle Cancer Care Alliance, its medical staff or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you. Introduction Andrew Schorr: Hello and welcome once again to Patient Power, sponsored by the Seattle Cancer Care Alliance. I'm Andrew Schorr. One of the areas that has been daunting, if you will, in some parts of it is gynecologic cancers. Ovarian cancer has been such a devastating diagnosis for women because it's usually discovered late and often leads to a high mortality rate. There are other gynecologic cancers too, cervical cancer and endometrial cancer. We're going to talk about that today with the director of the gynecologic oncology program at the Seattle Cancer Care Alliance and get an update for women and families touched by any of these conditions and also talk about what can we do nowadays about prevention and where are we with research and doing better in the treatment of these illnesses. With me is Benjamin Greer. Dr. Greer is the director of the gynecologic oncology program at the Seattle Cancer Care Alliance. He's also a professor in the department of obstetrics and gynecology at the University of Washington. Dr. Greer, welcome back to Patient Power. Dr. Greer: Andrew, thanks for having me back. It's nice to chat with you again. Andrew Schorr: Dr. Greer, so let's start first of all with the deadliest of all of these cancers, ovarian cancer. Women worry about this and often someone has a friend and they're angry it's discovered late, and the fear has been there's not much that can be done. So first of all, why is ovarian cancer typically discovered late? What's been the problem there? And do we have any clues that might help us discover it earlier when there's more you can do? Discovering Cancer Early Dr. Greer: Well, the main reason that ovarian cancer is diagnosed late is we don't have any tests that can easily predict the pre-onset phase of ovarian cancer. Consequently, the majority of patients have spread from the ovary in the abdomen or possibly to www.patientpower.info sccapatientpower.org SCCA052108/0606/AS/jf © 2008 Seattle Cancer Care Alliance All Rights Reserved 2 have fluid on their lungs with malignant cells so they are stage III or stage IV cancer when diagnosed. Andrew Schorr: Where are we with what we can do in that situation? And maybe along the way help us understand, what are the diagnostics you do these days to just understand how far the cancer has advanced? Dr. Greer: A couple of things. We Hutchinson center have an ovarian spore project that has been ongoing for over a decade looking at ways to try and diagnose ovarian cancer through screening means using blood tests as a marker. Unfortunately to date we have not been successful in identifying an appropriate test. The other piece of information that is being developed is a symptom index that has been led by the division of gyn oncology. Basically this is an attempt to look at a woman's symptoms that usually are abdominal complaints based on bloating and change in GI, gastrointestinal function that can predict whether or not an individual may be at risk for ovarian cancer. Basically women who have chronic gastrointestinal complaints probably aren't at risk, but someone that has more recent onset of complaints may be someone with ovarian cancer and need to be evaluated. Andrew Schorr: So when we talked about it being discovered often at stage III or stage IV, what do you do at that time? Is that a surgical approach or surgical and chemotherapy? What are you doing now at the SCCA? Dr. Greer: Usually when someone is diagnosed that they have either a palpable pelvic mass or they've had a CT scan that demonstrates that there is either a pelvic mass with ascites, which is fluid in the abdomen, and evidence of involvement of the omentum, which is the fatty pad in the abdomen that we have, and this is an indication for a surgical approach. The main first step in ovarian cancer is what we call tumor reductive surgery where one tries to remove the uterus tubes, ovaries and as much of the tumor that is resectable ideally to resect the disease down to individual aggregates that are one centimeter or less. A centimeter is a little less than a half an inch in diameter. Chemotherapy is then the next step, which usually is a combination of a drug called Taxol and a drug called carboplatin, which are given every three weeks for six cycles to evaluate at the end of that time the status of their disease. The majority of women will respond to surgery plus chemotherapy. Unfortunately there are still a fairly high recurrence rate even after initial remission of their disease. www.patientpower.info sccapatientpower.org SCCA052108/0606/AS/jf © 2008 Seattle Cancer Care Alliance All Rights Reserved 3 Andrew Schorr: So where are we with trying new things? We've heard about these antiangiogenesis drugs trying to stop the blood supply to the tumor cells. Where are we with that and some drugs maybe that are either totally in research now or drugs that have been approved for other cancers? Dr. Greer: The antiangiogenesis drug called Avastin was in a gynecologic oncology trial in patients that had failed other regimens with a good response rate. That was published last year. The ongoing gynecologic oncology trial is a trial that has Taxol and carboplatin as one arm; Taxol, carboplatin plus Avastin for six cycles; and then there is a third arm that's Taxol, carboplatin and Avastin for six cycles; and then the Avastin is given on as a maintenance drug. So this is really testing two different premises. One is that Avastin may improve the outcome over just Taxol and carboplatin and then testing the idea does maintenance therapy have benefit in this group of patients. This is an ongoing study. It's a randomized controlled trial. Andrew Schorr: You have at the Seattle Cancer Care Alliance of course many clinical trials that are under way including in gynecologic cancers. Where are you with other kinds of drugs that are in development maybe following the same idea of antiangiogenesis? Drugs Developments for Gynecological Cancers Dr. Greer: There is a large number of antiangiogenesis drugs that are in development, and we have several of those that have been evaluated at the Seattle Cancer Care Alliance. Some of these studies are in patients that have failed other regimens, other drug regimens, and sometimes it's the second or third failed regimen that these patients are tried on. Obviously any of these studies, patients have to have certain eligibility criteria to participate in these studies, and it requires that they be evaluated and then potentially consented and treated. The other drugs that have shown activity in ovarian cancer are topotecan, Doxil, which is a liposomal Adriamycin product, and then Gemzar or gemcitabine. These have recently been tested in a variety of combinations with Taxol and carboplatin as first line agents, and preliminary results of that gynecologic oncology trial doesn't demonstrate any advantage of these agents over Taxol and carboplatin alone. They are important in terms of women who fail or relapse after being initially treated with Taxol and carboplatin. They have different toxicity profiles depending on the patient, and their medical condition selection is kind of individualized for the given patient. Andrew Schorr: Well, I'm noticing as I look on the SCCA website, which is terrific, where you can look by cancer type and what trials may be available, your name as principal investigator is there with numerous ones. So if someone comes to you at the Seattle Cancer Care Alliance and, let's say, they're diagnosed with ovarian cancer, www.patientpower.info sccapatientpower.org SCCA052108/0606/AS/jf © 2008 Seattle Cancer Care Alliance All Rights Reserved 4 it's discovered late, how you do you and that woman look at, say, what are the standard therapies you have and is there a clinical trial that maybe we should put on the table for discussion of whether this might be an opportunity for you? How do you have that discussion? What guidance would you give us? Dr. Greer: Well, I think first I just want to point out the philosophical issue that I have with patients. Most patients that get diagnosed with ovarian cancer, either they or their friends and family go to the internet and get very discouraged about potential outcome. And I always tell patients that the only person that really counts is what happens to that individual, and that you don't know who is going to win until you play, and the object is to try and get the best response and the best outcome for the patient. We try to as we see patients evaluate them for the possibility of a clinical trial, and if they are eligible for a clinical trial is to offer the trial to the patient and sit down and thoroughly go over all the details of what it entails to be part of a clinical trial, and if they accept obviously we then carry forward with the trial. There is oftentimes reasons why patients cannot participate in trials. One of the examples would be some woman who may have had a breast cancer two years ago. Because of the rules of the trial they wouldn't be eligible to participate in a clinical trial, and those individuals would be treated with standard combinations of drug depending on the site of disease. Andrew Schorr: As we look overall with ovarian cancer then, how do you feel about things? For instance we're starting to hear about trying to identify genes that may be at risk. My producer was mentioning to me there has been talk about the loss of the GPC3 gene and maybe there was a connection to ovarian cancer. We're learning who may be at risk so that people can have surveillance and hopefully we don't get to the situation where it's discovered late. Dr. Greer: The genetic literature is quickly exploding in terms of new information that could be applied to patients that potentially are at risk. With the completion of the genome project it's provided the alphabet, if you will, that can look at different genes and then what are at risk. In ovarian cancer probably the BRCA1 and 2 story is the best story that's available, and the patients that have those genes are at risk for ovarian cancer as well as breast cancer. Andrew Schorr: Well, follow-up then, you see women who are diagnosed with ovarian cancer. Are they typically worked up genetically to see might there be a reason for testing for BRCA1 and 2 and if so then have a consultation with their family? Dr. Greer: When we see patients we try to investigate their cancer history within the family and if they are looked to potentially be at risk for a BRCA1 or 2 mutation is that we www.patientpower.info sccapatientpower.org SCCA052108/0606/AS/jf © 2008 Seattle Cancer Care Alliance All Rights Reserved 5 refer them to the high-risk breast and ovarian cancer clinic at the SCCA. That clinic has genetic counselors that do prescreening and take an extensive family pedigree, and then the patient is seen and then counseled about genetic testing. The major kind of things that we look for are other first-degree relatives that have ovarian cancer and then also women who are of Jewish heritage also are at risk, especially the Ashkenazi Jewish population. The patient that is at risk is to have the individual who has the disease be evaluated for the genetic abnormality, and if they're negative then that would mean that their offspring would not be at risk. If they are positive then there's the possibility that children or grandchildren of that individual may be at risk. One has to also remember that the BRCA1 gene can be transmitted genetically through a male child of the patient, and so this needs to be kept in mind when looking at this genetic risk. Andrew Schorr: Wow. Lots to talk about. So is there anything we can do besides ultimately genetic evaluation to prevent ovarian cancer? Dr. Greer: We have people that have genetic abnormalities that we offer prophylactic removal of both the ovary and fallopian tube. We identified as have other centers that some ovarian cancers may actually begin in the fallopian tube, and in our experience we have discovered early fallopian tube cancers during prophylactic surgery. There are other things. Women who have been on oral contraceptives has a protective effect of developing ovarian cancer. In addition women that have more I don't know how to describe it you know, have multiple children are at less risk for ovarian cancer. The concept behind ovarian cancer revolves around ovulation potentially as an inciting factor in the ovarian cancer process. Most of the time we often talk about the avian model where if you take a hen and let them ovulate for their lifetime and then at year seven sacrifice the hen and do an autopsy that 60 percent of those will have an ovarian cancer-like process going on. Andrew Schorr: So in other words, fewer periods as you'd have when you're pregnant would be better then, it sounds like. Dr. Greer: That's correct. Andrew Schorr: Wow. Well, a lot more to learn from that. Well, I wish you well with the progress in ovarian cancer with its high mortality rate, although I hear you say clearly that every woman needs to understand her situation as a unique one and that's the discussion they have with specialists like you as they seek treatment. Let's talk about a couple of other gynecologic cancers in the time that's left. Now, in cervical cancer we have made progress, haven't we? www.patientpower.info sccapatientpower.org SCCA052108/0606/AS/jf © 2008 Seattle Cancer Care Alliance All Rights Reserved 6 Dr. Greer: Cervical cancer, the number of cervix cancers per year is below 10,000 annually at this time. This is predominantly due to cytologic screening with the pap smear or cervical cytology using a liquid-based cytology method which is probably the most common. So we have and that pre-invasive cancer lesions are identified and can be treated and therefore reduce the risk of the patient. One of the major advances in treating advanced cervical cancer is the addition of chemotherapy during the radiation. There was an NCI alert several years ago citing five different randomized controlled trials demonstrating survival advantage by combining chemotherapy and radiation together. Ordinarily the radiation is given daily Monday through Friday and one of the days the patient receives chemotherapy, which is usually cisplatin as a single agent at a fairly low dose, and this has improved the outcome in cervical cancer patients. HPV Vaccine and Gynecological Cancers Andrew Schorr: Now, what about the vaccine, the HPV vaccine? Where does that come in in helping our daughters and young women? Dr. Greer: The vaccine I think is a great advance. The one that is currently on the market is what we call a quadrant valent vaccine, which is against HPV virus number six, 11, 16 and 18. 16 and 18 are the ones that are associated with cervical cancer risk. Six and 11 can cause other noncancers, GYN complaints, which obviously the vaccine can't do that. And the recommendations are for women between 12 and 26 to potentially be vaccinated. This, as much as I think it's going to be a great advance, it's going to be probably 15, 20 years or more before we see the total impact of the vaccine because women who are already at risk would not be candidates for the vaccine. The other is that we are recommending, at least until we learn more, not to change screening practices in women that get the vaccine because only about 70 percent of cervical cancers are going to be prevented by the vaccine so that there still is a risk of developing cervical cancer that's probably due to some other HPV viral environment that we don't have vaccines for at this time. Andrew Schorr: For where the vaccine is effective though, if a woman has already had sexual relations, been exposed to HPV, which I understand is in so many of us, then would the vaccine work? Or would you have to receive the vaccine before any exposure? Dr. Greer: The ideal patient is someone who has not been infected by HPV viruses. There's ongoing evaluations of women who may have had an HPV infection and to see what the protection of the vaccines will be, but those are ongoing studies. The other www.patientpower.info sccapatientpower.org SCCA052108/0606/AS/jf © 2008 Seattle Cancer Care Alliance All Rights Reserved 7 studies that are ongoing is since we think that most HPV infections are sexually transmitted there is ongoing HPV vaccine studies in males trying to see if that part of the cohort can be the incidence be reduced. Andrew Schorr: Okay. Well, still a lot to learn. One other gynecologic cancer I wanted to talk about was endometrial, which I understand out of the 78,000 annual gynecologic cancers that are diagnosed in the US endometrial is the most common. Where are we now in improving our therapy there? Improving Therapies for Endometrial Cancer Dr. Greer: Endometrial cancer is usually in an older population, and usually you have bleeding as a sign of potential cancer and can be evaluated by having an endometrial biopsy, which can be done as an office procedure. And if the diagnosis of endometrial cancer is established then we recommend primary surgery, which would include the removal of the uterus, tubes, ovaries, doing what we call a peritoneal cytology, which is obtaining fluid from the abdominal cavity and doing like a pap smear on it. In addition is to do a lymph node dissection of the pelvis and periaortic area to determine if the cancer has spread to the lymph nodes. After all this information is gathered I look at this as an assessment of the various risk factors, and depending on the risk factors the patient may not require any additional treatment. Fortunately, 85 percent of patients who have endometrial cancer fall into what I call a low-risk group and just require surveillance with pap smears and pelvic exams. The other 15 percent require additional treatment and sometimes it's local radiation to the vaginal apex or radiation and/or chemotherapy for management of disease that is beyond the confines of the uterus. There has been some changing philosophies including more chemotherapy regimens along with radiation or even just chemotherapy as the only adjuvant treatment. Andrew Schorr: Dr. Greer, I know we're talking about different sites, endometrial, cervical, ovarian and then maybe different sub types as we learn more about the biology of each woman's cancer, but in your field of gynecologic oncology how are we doing? I mean, there are some areas of cancer we feel, whoa, things are changing dramatically and others where it's been slower. How do you feel about how we're doing and what hope we can offer women today and the importance understanding their own individual situation? Dr. Greer: In terms of the field of oncology I think gyn oncology is doing very well. More than 70 percent of the patients that have gynecologic cancers can be cured. And we spoke earlier about ovarian cancer and it not being as well controlled because of its advanced stage when diagnosed, but I think overall women with gynecologic cancers have a good outcome in terms of the outlook for their diseases. www.patientpower.info sccapatientpower.org SCCA052108/0606/AS/jf © 2008 Seattle Cancer Care Alliance All Rights Reserved 8 Andrew Schorr: And as far as research, since you're at a research institution as you look at what's going on in the labs, are you encouraged? Do you see a lot of promise there? Dr. Greer: We've touched on the genetic aspect of some of these diseases, and I think as the field is moving rapidly I think genetic evaluations may become a part of the screening process. We just are completing in the Gynecologic Oncology Group a study looking at molecular profiling of endometrial cancer, which is trying to look at biochemical changes in the cancer cells themselves to try to evaluate outcome and see if we can do predictions of outcome based on this information. This study has not been completed, but I think it will provide us with valuable information. Molecular evaluation in breast cancer outcomes has been significant in terms of treating breast cancer, and I think it will be similar in endometrial cancer when we complete this study. Andrew Schorr: There's some neat work going on in your institution. I know we just did a program with Dr. Evan Yu about cancer biomarkers, and as you're saying like in ovarian you don't have the perfect one yet, but, boy, it would be great if that could be developed. And then also the molecular, understanding you're talking about as now in breast cancer understanding which woman will be a candidate for which treatments, chemotherapies, etc., and where it's likely to respond. That would be so helpful, too. Well, Dr. Benjamin Greer, director of gynecologic oncology at the Seattle Cancer Care Alliance, and professor in the department of obstetrics and gynecology at the University of Washington, thank you so much for being with us and helping us understand an update. And also it always underscores for me when I talk to you, sir, of how important it is and I would really mention this in this case for women if you're diagnosed with one of these illnesses I really would recommend a consultation with a sub specialist such as Dr. Greer and what they offer at the Seattle Cancer Care Alliance. It really can give you the best knowledge of what may apply to your specific situation today and also is there research going on that might be helpful to you as well. Dr. Greer, thanks for being with us. Dr. Greer: Andrew, thanks. It's been a pleasure. www.patientpower.info sccapatientpower.org SCCA052108/0606/AS/jf © 2008 Seattle Cancer Care Alliance All Rights Reserved 9 Andrew Schorr: And I will just mention that our next program will be with Dr. Mike Mulligan, who has been on Patient Power as well before, just like Dr. Greer. And we'll be discussing minimally invasive video assisted thoracic surgery or VAT surgery for people afflicted with lung cancer. Thank you so much for joining us. As always, knowledge can be the best medicine of all. For the Seattle Cancer Care Alliance, I'm Andrew Schorr. Please remember the opinions expressed on Patient Power are not necessarily the views of Seattle Cancer Care Alliance, its medical staff or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you. . and therefore reduce the risk of the patient. One of the major advances in treating advanced cervical cancer is the addition of chemotherapy during the. what about the vaccine, the HPV vaccine? Where does that come in in helping our daughters and young women? Dr. Greer: The vaccine I think is a great