First, realize that this whole process may not be right for you. If that is the case, feel free to discard this whole discussion. Or maybe, you might be comfortable with only part of the process. Whatever works for you is right for you.
Secondly, I want to emphasize that I make mistakes and the choices I make are/were right for me and no one else. Right or wrong, this is how I went through the process. My reasoning may be based on false understanding of ovarian cancer in general or based on a false understanding of my specific situation. But, at some point, I had to go with what I believed to be the best option for me at a specific point in time. The next time I go through this process, my answers may be entirely different.
From here on, these examples of questions are applicable to only myself and to no one else. These are just examples. You must answer each question in your own way for the answers to be valid for you.
1. What is your personal treatment goal? To my mind, there are four treatment goals:
Prior to making my final decision about a specific treatment, I thought about the following things on a personal level:
b. Reduction in size of cancer
c. Reduction of symptoms
d. Stabilization (no growth or minimal growth) of the amount of the cancer.
2. How did I answer Questions which I asked my physicians? (See next section just below)
3. How would this treatment affect our life??? Specifically, I thought about financial requirements, our jobs, geographic location of trial versus the need/costs for travel and the disconnection from family and support systems, the treatment method versus quality of life, etc.
4. Have I included my family and care-givers in this decision? However, the final decision was mine and mine alone. After all, I am the one who will have to deal with the side effects of treatment and the cancer.
Note: Thanks to my physician E.K. for this organized version of questions.
1. How much toxicity (nasty side effects) am I willing to accept for how much potential benefit? Do I believe that nasty side effects are required for the treatment to be effective? Some people do, you know... How might the side effects of this treatment affect the quality of my life? Can I still work? Go on vacations? etc. Are the side effects permanent? Is there anything that can be done to lessen or prevent the side effects?
2. Is the potential for risk worth the potential for benefit? Is the risk of death or serious disability very high but the potential for benefit about the same as any other treatment? Can it impair any sensory organ, such as sight? Can it increase existing chemo side effects, such as increased hearing loss or neuropathy (numbness or tingling)? Can it damage any major organ?
3. Do I have any pre-existing health conditions which might eliminate some choices? Examples might be high blood pressure, heart conditions, liver conditions, kidney conditions, low blood counts, etc.
4. How fast is the cancer growing versus how fast does the therapy work? Chemotherapy drugs have the potential to work more rapidly when compared to something like an immunotherpy (vaccine or an anti-angiogenic agent which were discussed in the November 2001 issue of Conversations). Don't run on your feelings about this. Ask your physician as he/she has a better feel, born of experience, about this.
5. Are any "end" organs at risk? Is the cancer on or near a major organ (liver, lungs, colon, etc.)? Should a specific therapy be chosen because it might be more likely to work than a clinical trial? Should a specific therapy be chosen because it might work faster? Again, ask your physician's advice about this.
These thoughts are only applicable to me and not to anyone else. I offer them only as a example of the process which I used.
1. Do nothing.
2. Wait for more growth and then do surgery to obtain tissue for chemo-sensitivity testing and genetic testing.
3. Try the hormonal antagonist agents.
4. Try any of the second line of chemotherapy drugs (listed in no particular order):
VP-16 (etoposide, VePesid)
doxil (liposomal doxorubicin)
xeloda (capecitabine or encapsulated form of 5-FU)
camptosar (CPT-11, irinotecan)
5. Try a clinical trial - but how to pick one??? First I had to locate a listing of clinical trials (see below). On the day when I did this search, it displayed a listing of more than 40 clinical trials which fit my selected criteria. Obviously that number can be over-whelming...hence, the following discussion.
If you want to try something different, consider a clinical trial. Women are alive and well today because they tried carboplatin, cisplatin, cytoxan, or taxol when those drugs were considered to be experimental. By participating in a trial, you may extend your own life and will certainly be instrumental in helping to find new and improved treatment options. For general clinical trial info, call 1-800-4CANCER and ask for their booklet which explains clinical trials; OR go to NCI's site and click on Understanding Clinical Trials. Be sure to thoroughly understand the risks specific to each clinical trial before enrolling. How to locate the current clinical trials that fit your need??? Not all anti-angiogenic or gene therapy or Herceptin trials are identical. There are many variations at many different sites around the country. Your search will be much more effective if you know the criteria which would be specific for your individual situation. Whether you phone or search via the web, your search will be more effective if you already know the answers to question #4 at the bottom of this page, especially the one about specific cell type.
Some have "notification services" which will automatically send you e-mails when new listings are posted.
1. National Cancer Institute (NCI). Call toll free 800-4CANCER or search their web site, Cancer Trials. http://www.cancer.gov or when it's "busy," use the "back door," http://www.nci.nih.gov , click "cancer trials"
2. United Kingdom's version of NCI, http://www.graylab.ac.uk/cancerweb/trials.html
3. Ov Ca Research Notebook http://www.slip.net/~mcdavis/ovarian.html by National Ovarian Cancer Association (Canada).
4. Clinical trials run by individual comprehensive cancer centers, but not sponsored (paid) by NCI, are NOT usually listed by the above sources. For listings of the NCI's Comprehensive Cancer Centers, see pages 10 and 11 of this issue. Or click on the links to individual Centers at http://www.nci.nih.gov/cancercenters/centerslist.html. At each cancer center's web site, click on their "clinical trials", "patient resources", or "treatment" areas.
5. CyberMedTrials at http://www.cybermedtrials.com
6. Acurian, Inc. Ovarian cancer hotline is 866-566-2653; http://www.acurian.com sponsored by the global pharmaceutical and biotechnology industries.
7. Cancer Watch 617-856-5900 http://www.centerwatch.com ; similar to Acurian.
To locate a clinical trial, NCI's Cancer Trials telephone hotline or web site (#1 above) is probably the best way to get lists of NCI sponsored trials. Other services of NCI and its site feature research news, built-in definition of terms (click on underlined/colored words), and easy access to other resources. If you don't understand any of the terms below, NCI's booklet or web section "Understanding Clinical Trials" will be useful. Trials open and close daily so check frequently. Using NCI's web site, do the following for the broadest possible search results. Anything else will produce fewer options (trials):
1. Go to http://www.cancer.gov
2. The first screen has two columns of choices. In the left column, click on "Finding trials"
3. The second screen has two columns. In the left column, click on "PDQ's Search Form"
4. Now you are faced with a series of boxes. From top to bottom:
a. Type of cancer: Click and scroll down to desired cancer. "Ovarian cancer" gives you 5 choices as to cell type: germ cell, epithelial, low malignant potential, sarcoma, or stromal cell. Until you can ask your doctor, pick the most common cell type "epithelial." This is an extremely critical criteria so verify it with your doctor.
b. Type of trial: Click and scroll down to "treatment" which is what anyone already diagnosed will want.
c. Status of trial: leave button set to "open" which means they are still seeking patients for the trial.
d. Protocol number: Leave blank. Each trial is assigned a unique protocol number as an identifier. Unless you already know which number you want, leave this blank.
e. Location of trials: This search often only finds the location of the principal investigator. It does not find the locations where the trial is actually being done. If a trial is interesting to you, ask your physician to determine if the trial is being offered close to home. Therefore, for broadest search: City: leave blank. State: leave set to "all states" Country: leave set to "all countries"
f. NIH Clinical Trials Center Only: leave box blank unless you want only those offered at the Bethesda, MD location.
g. Version of Results: according to your preference, choose either "health professional" or "patient"
5. Then click the "search" button.
6. On the next screen, you are told "Your search retrieved __ clinical trials...." You can choose "display results"...or... "narrow your search further."
7. I find it helpful to "narrow the search further." After making that choice, the next screen asks
a. Stage of cancer: Unless you are newly diagnosed, the most useful choice is "treatment" or "recurrent"
b. Modality: Set to "all." Any other choice limits your choices dramatically. Trials may have combinations (such as vaccine with "an anti-angiogenic agent and a standard chemo drug) or use terms differently than you might.
c. Drug: leave blank
d. Phase of trial: Set to "all." This refers to phase I or II or III. Meaning of "phase" is explained in NCI's booklet and web site. Also see the discussion on page 9-10.
e. Sponsor of trial: select "all"
f. Clinical trials added to PDQ this month: leave blank unless you want only those new this month
8. Then click the "search" button.
9. Look at list. Click boxes of any trial in which you are interested. Then you can read the details about that trial.
10. If there are too many, narrow the auto selection (boxes). Go back to step 4 and limit the various categories.
11. Print off the list of clinical trials, especially if you find it easier to work on paper.
These thoughts are only applicable to me and not to anyone else. I offer this only as a example of the process which I used.
Note: As I worked through these thoughts, I took my trusty pen and crossed off those trials which were eliminated from the paper version listing that I had just created. I work first the "easy to eliminate as option" and then the "harder to decide".
1. Any trial which uses taxol (paclitaxel), carboplatin (paraplatin), or cisplatin (platinol) was eliminated as a potential treatment as I think it is too soon to try these chemos again after they didn't get all of the cancer in fall of 2000 or spring of 2001. I may consider using them later as there is evidence they work again after a "time off" period of a year or longer. I may consider using them as weekly low dose type treatments as there is evidence that they work differently, perhaps as anti-angiogenic agents to prevent blood vessel formation in cancer tumors.
2. Any trial which uses docetaxel (taxotere) as that chemotherapy drug is too closely related to taxol.
3. Any trial which used oxaliplatin as that chemotherapy drug is too closely related to carboplatin and cisplatin.
4. Any trial which uses high dose chemotherapy followed by stem cell transplant. The risks are very high. High dose chemo is extremely damaging to quality of life for an extensive time period. The potential for working as a treatment for recurrent ovca isn't better than the more traditional chemo. Results in other cancers and in ovca trials have been disappointing. It may still have potential as an initial treatment after diagnosis or immediately after initial treatment, but I'm not interested.
5. Any trial which uses intra-peritoneal (IP or through an abdominal port) chemo or gene therapy. Substances delivered IP must touch the cancer. With multiple surgeries and my tendency to scar, the fluid given IP would not likely reach all the locations of the cancer in the abdomen. If the cancer is in the lymph nodes, outside the abdomen, or part of a large "ball", IP therapy may not work.
6. Any phase 1 trial in which the goal is to determine the maximum tolerated dose of a substance completely new to human clinical trials. This may be an option for later, but not right now. (See #7 for exceptions.)
7. Note: I did not initially eliminate those drugs which were in phase 1 trials for ovarian cancer, but had successfully been tried in other cancers. This took some real detective work to determine if the drug had been used before in cancers other than ovarian cancer.
8. Any phase 1 trial which uses a combination of two chemotherapy drugs known to potentially work on ovarian cancer as that combination could probably be obtained off a clinical trial at a later date if they prove to be a feasible, tolerable, and effective combination. (A partial list of chemotherapy drugs is at the bottom of page 3.) An example of one combination in trial is gemcitibine (gemzar) together with topotecan (hycamtin).
9. Any trial using herceptin (traxtuzamab) or which requires her-2/neu over-expressing ovarian cancers. My tumor has been checked and does not over-express the her-2/neu gene.
10. Any trial which uses a drug which can be obtained off-trial. The most prominent example I saw is thalidomide (thalomid) which is thought to be anti-angiogenic (prevents/limits blood vessels from forming, thus prevents/limits tumor growth).
11. Any trial which did not limit the number of prior rounds of treatments unless it was clearly a better option.
12. In general, any treatment which I can do at any time in the future was eliminated unless it was clearly a better option.
1. How does the hoped-for outcome match my treatment goal?
2. What does my doctor think about this treatment as an option for me, knowing my specific situation? I consulted with my own oncologist throughout the process to make sure that I understood as much as possible what options are open to me and what might work in my individual situation. I scheduled an extended appointment time to just talk about these treatment options.
3. Should I seek a second opinion? It is not likely that I will find a consensus of opinions regarding treatment options, I think a limited search is worthwhile. However, after the first round of chemo treatment, I know that there is not a recognized "next step" as to what is the best way to go as so much depends on my individual situation.
4. What is the experience of others who have taken this treatment? Paper mail or e-mail works, but the increased cost of phone calls is well worth the improved exchan ge of information. Networking is the best source of this type of information so I utilized the matching list of this Newsletter and went to the Ovarian Problems List. Archives are at http://www.acor.org . With about 1300 subscribers who read the List daily, there is a high probability of finding a match. To subscribe, send an e-mail to firstname.lastname@example.org and in message area, type in "Subscribe ovarian" followed by your name. (I would type "Subscribe ovarian Cindy Melancon")
I am interested in knowing the results with: Any type of cancer? In ovarian cancer? By itself (as a single agent)? In combination with another agent or treatment method? What were the reported side effects? Resources where I might find this information:
American Society of Clinical Oncologists (ASCO) at http://www.asco.org and click on "abstracts" from previous annual meetings, organization for treatment oriented research for any kind of cancer, can search on key words, but language is written by docs for docs so highly technical.
Society of Gynecologic Oncologists (SGO) at http://www.sgo.org ; same as ASCO but at times, less treatment oriented
Ovarian Cancer Research Notebook of the National Ovarian Cancer Association (Canada) is a good news finding site for ovca-oriented information http://www.slip.net/~mcdavis/ovarian.html ; easy to follow the results of trials for about the past 5 years, organized into categories so easy to search
Commercial health-related research firms. An example is: The Health Resource, Inc. (800-949-0090 or http://www.thehealthresource.com ) owned by an ovca survivor
After eliminating those which you feel to be wrong for you at this time, research the remainders in detail. This brings it down to a more manageable number for final consideration. Next, on the web site I clicked the boxes next to those more interesting trials and printed out the "health professional" versions. You can request these detailed versions from the NCI via their Hotline as well.
This was based on "protocol entry criteria" as listed in the "health professional" print-out of each trial.
1. Any trial which excluded those who have had more than 2 or 3 prior treatments or cycles. (The 6 treatments of cytoxan and carboplatin in Feb 1992 count as one cycle, the 6 treatments of carboplatin and taxol in fall 2000 count as the second cycle, and the 6 weeks of cisplatin and radiation in spring 2001 counts as the third cycle.) However, if the trial is one in which you are interested, the web version is not always accurate so ask your physician to check with the principal investigator. Clearly, I was right on the border of being eliminated from some, but not all, trials based on prior treatments. If you are on the border and you are really interested in a specific trial, check further.
2. Any trial which excluded those who have had partial abdominal radiation.
3. Any trial which excluded those who have had certain chemotherapy drugs.
Note: In cancer treatment trials,a placebo or sugar pill is never used.
Phase 1 clinical trials: Generally phase 1 trials are designed to determine the maximum safe dose and the maximum dose compared to unacceptable side effects. Sometimes the effect of the treatment on the cancer is reported at the trial's conclusion, but that is not the primary purpose of a phase 1 trial. Very small numbers of patients are enrolled in the trial (usually less than 50). Any kind of cancer is usually acceptable and there are not usually any limitations on the prior number of treatment cycles. A second type of phase 1 trial is used to test a drug which has been proven (through phase 1 or 2 or 3 trials) to work in one kind of cancer, but will now be tested on a different cancer. A third group of phase 1 trials are those in which two drugs which were previously tested as individual treatments begin testing in a phase 1 trial which combined the two drugs.
Phase 2 clinical trials enroll very few patients (usually less than 100-200). They are designed to determine if the treatment works on a specific type of cancer. Some limit the number of prior treatment cycles to less than 2 or 3, including the initial treatment and a treatment for recurrence. Others have no limitation on prior treatments.
Phase 3 clinical trials usually enroll large numbers of patients (several hundred or more) and are designed to compare the new therapy with the current standard treatment....in other words, which one works best. These trials are most likely to involve comparison to one or more groups which may be getting different treatments. However, these are the least experimental as all of the treatments are proven therapies.
BY NOW, YOU ARE DOWN TO JUST A FEW CLINICAL TRIALS WORTHY OF FURTHER INVESTIGATION.
Specific questions to ask about each clinical trial...Some of this information you may be able to gain by reading the description of the trial or discussing the description with your current oncologist. But it may be time to go for a formal consult with the principal investigator or the co-investigator who lives closer to your home.
1. What is the treatment and how does it work?
2. How is the treatment given? IV or through a vein? A pill? A shot? IP or intra-peritoneally through a port into the abdomen?
3. How often is the treatment given? Daily, once weekly, several times each week, once monthly, etc.
4. What are the expected side effects? How are these handled? What are the worst side effects that have happened and how often? Are the side effects permanent or reversible? Is there anything that can be done to prevent or limit the side effects?
5. Will this treatment alter the accuracy of the CA-125 test now or in the future? Permanently or temporarily?
6. How is success defined? Let's say that the trial involves taking a vaccine. Is success defined as "there was an immune response shown in blood levels"? Or is it defined as "there was a clinical response", such as the CA-125 level dropped or the size of the tumor on a CT scan became smaller? To me, it is more important that a clinical response was seen. I consider this difference to be extremely important in picking out a clinical trial.
7. How am I monitored during the trial? Blood tests, CT scans, physical exams, etc. How often?
8. When does the treatment end? Some trials end at a certain number of treatments, regardless of whether the treatment is working or not. In other trials, the treatment for an individual continues until it stops working. To me, this is a big consideration.
9. How many have enrolled so far? What is the desired enrollment before the trial is closed to enrollment? Am I among the first to enroll in the trial or among the last? If you are among the last, then you may benefit from the experience of the first ones. However, if this is a treatment which has worked well in an earlier ovarian cancer trial or in other cancers, you may want to be among the first to enroll.
10. If the trial is being run from a distance from my home, do I need to go to the center each time for my treatment? Or can the treatment be done by an oncologist nearer to home? How often do I need to go? How long do I have to stay each time?
11. Are there any procedures required prior to enrollment? During the trial? After the trial is over? How often? Risks?
12. Are there any surgeries required prior to enrollment? During the trial? After the trial is over? How often? Risks?
13. Any hospital stays? How long?
14. Financial costs for me? Covered by insurance or Medicare?
15. Is it likely to limit participation in future clinical trials? For example, some chemotherapy drugs now in trial may disqualify you from taking another drug in the same class.
1. Basically, leave your options as open as possible and then print out all the options that come up for recurrence and for treatment. If you are using the NCI Hotline, request that a print out of all the options be mailed to you.
2. On the printout, look at the title of each trial. Eliminate those which include drugs you have already taken without success.
3. On the print-out, scratch off those trials not in the "phase" which interests you. (See the section just above on this page.)
4. Then read the detailed description (health care professional version) of those left.
5. If the enrollment criteria excludes enrollment because of a type of chemotherapy you have already taken or because of the number of previous chemotherapy treatments, cross those off.
6. If you see some requirement, such as surgery, that you are not willing to do, cross those off the list.
7. Then investigate each trial thoroughly to determine how each matches with your interests.