Ovarian cancer most commonly is diagnosed at an advanced stage of disease. 75-80% of the time women are found to have stage III or IV cancer at the time of diagnosis. This means the cancer has spread from the ovaries to other pelvic and abdominal organs or lymph nodes in the pelvis, groin or abdomen (Stage III) or has spread outside to the liver or outside the abdomen, most commonly to the lining around the lungs (Stage IV).

5 Important points to consider

When ovarian cancer recurs, there are many treatment options available for patients. The decision regarding what option is best depends on many things.

Several of the important issues to consider when choosing a treatment include:

1) Time to recurrence

How long since your last chemotherapy?

How well you may respond to therapy and which therapy depends on how well it worked before. The longer time off chemotherapy usually correlates to a better response to repeating the same type of therapy

2) Toxicity of previous therapies/ toxicity of new therapy

What was the worst toxicity of side effect of your previous chemotherapy?

What side effects would be the worst for you to have with more chemotherapy?

3) Delivery schedule and ease of administration of a therapy

Is a weekly schedule or monthly schedule of chemotherapy easier for you?

Is intravenous (IV) access a problem for you?

4) Quality of life issues

Since treatment for recurrent ovarian cancer is aimed at controlling the disease and extending life rather than curing the cancer, it is important to consider what is important for keeping good quality in your life

5) Investigational therapies

What is a clinical trial?

Are you a candidate for a clinical trial?

As a general rule, if it has been 6 months or more since you received primary chemotherapy when your cancer recurs, you are considered to have "platinum-sensitive" or "chemotherapy sensitive" disease.

-If you fit this category re-treatment with a platinum-containing regimen is commonly the first choice of therapy. The longer it has been since previous therapy the more likely it will work.

-Response rates vary from 20-60%

-For women who have been off therapy for more than 2 years, response rates to re-treatment approach that of primary therapy, 70-80%

-Platinum agents, carboplatin or cisplatin, have been around the longest, so there is more information about re-treating with these agents than with a taxane, such as taxol or taxotere.

-Considering toxicities, and quality of life, most doctors will re-treat at recurrence with a single chemotherapy agent, usually Carboplatin, because it is so well tolerated.

-Carboplatin is usually given once every 3 to 4 weeks IV over one hour.

-The major toxicities of Carboplatin are nausea and lowered white blood count or platelet count. Hair loss rarely, if ever, occurs

-There are no studies to show that re-treating with both Carboplatin and Taxol is better than either agent alone, and toxicity, especially hair loss and neuropathy certainly increase with the combination

-If Carboplatin alone is used but does not work taxol or taxotere alone is often the next best choice.

-Taxol can be given on the usually every 3 week schedule, or on a weekly schedule.

- The weekly schedule of taxol reportedly causes less lowering of the white blood cell count and less hair loss, although hair loss is still common

- Taxotere, is another taxane which has less neuropathy that taxol, slightly less hair loss, but more lowering of the white blood cell count and changes of the nail beds, including loss of fingernails or toe nails

-Taxotere can be given every 3 weeks or weekly, similar to taxol

If your cancer recurs within less than 6 months of completing primary therapy, or grow while on primary therapy, or platinum therapy for recurrent cancer, your cancer is considered "platinum-resistant" or chemotherapy resistant."

If you fit this category, it is unlikely that re-treatment with chemotherapies that have been used before will work.

This is a category where many new agents have been found in recent years

All of these new agents have similar response rates.

The response rate is about 20-25%.

The average duration of response is 6-8 months.

This means that for 20-25% of women treated, their cancer will decrease in size by at least 50% for an average of 6 to 8 months.

Conversely for 75-80% of women, the treatment will not work and the cancer will continue to grow.

There is no proven way to determine which treatment will work for which person

So, when trying a new treatment for platinum-resistant ovarian cancer it is very important to consider:

This table lists the most commonly used agent with their most commonly used schedules and side effect profiles. Check with your doctor about specific dosing and schedules

Drug name (Trade name)	Route of administration and schedule	Major toxicities/Side effects
Topotecan	IV daily for 5 days over 15-30 minutes every 3 weeks Alternative schedule: weekly (investigational)	Lowering of white blood cell count 50% hair loss fever, headache, fatique and weakness (15-25%)-usually mild little nausea/vomiting
Doxil	IV over 1-3 hours once every 3 to 4 weeks	Skin changes- red, peeling skin of hands and feet, sometimes mouth sores Lowering of white blood cell count, nausea/vomiting less common Hair loss not common
Altretamine (Hexalen)	Pills given by mouth 3 times a day for 14 days every 21 or 28 days	Nausea/vomiting- can limit ability to take drug Lowering of white blood cell count less common
Etoposide (VP-16)	Pills given by mouth once a day for 14 days every 28 days	Lowering of the white blood cell count Hair loss Neuropathy less common Leukemia if given a long time
Gemcitabine (Gemzar)	IV over 15-30 minutes weekly for 3 out of 4 weeks	Lowering of the white blood cell count Fatigue- feeling tired Hair loss, nausea vomiting less common Rare, but serious lung damage that causes shortness of breath
Vinorelbine (Navelbine)	IV over 15 –30 minutes weekly for 3 out of 4 weeks	Lowering of the white blood cell count Pain at the tumor site during administration Neuropathy Nausea/vomiting/hair loss less common
Capecitabine (Xeloda)	Pills given by mouth twice a day with food for 14 days every 21 days	Skin changes- red, peeling skin of hands and feet, sometimes mouth sores Nausea/vomiting if not taken with food Lowering of white blood cell count less common

-Most of the studies done on these treatments that determine the response rates were in patients who had only received one previous chemotherapy (usually their primary therapy).

-So, if you have received several different kinds of chemotherapy, the chance of responding to another therapy may be different and is probably lower than reported response rates

-Although the response rates are low for these agents, there is an additional percentage of patients who will have "stable disease" on a treatment for a period of time. This means that although the cancer does not shrink significantly in size, it does not grow.

-If your cancer is stable on a treatment and you are tolerating it, most doctors recommend continuing that treatment as long as tolerated or until the cancer grows again.

- When starting a new treatment for recurrent ovarian cancer, it takes 2 to 4 cycles to determine if it is working.

-After 2 to 4 cycles, your doctor should evaluate if your cancer is responding to the treatment

-Most doctors do not recommend combining more than one drug for treatment of platinum-resistant ovarian cancer, because there is no evidence that a combination is better or that the responses last any longer, but a combination is definitely more toxic

-There is a test called the "Extreme Drug Resistance Assay" (EDR Assay) which involves taking cancer cells from your cancer, growing them on a plastic plate in the laboratory and testing the effects of many different chemotherapy treatments on them. This test is reported to show which drugs are least likely to work for your tumor

-This test has never been confirmed clinically, meaning what is shown in the lab has no been proven to be true in patients

-This test does not show which treatment will work for you

-It hypothetically shows which treatments will not work for you

The "anti-estrogen" Tamoxifen, which is commonly used in treating breast cancer, has some activity in ovarian cancer

Reported response rates to Tamoxifen are about 10-15%, and another 10-15% of patients treated will have a period of time of "stable disease", where the cancer neither grows nor shrinks

The side effects of Tamoxifen are mostly hot flashes and other menopausal symptoms

Since it has no effect on the white cell count, it can be used in patients who may not tolerate chemotherapy

Tamoxifen is a pill given by mouth twice a day every day

Other newer "anti-estrogen" agents used in breast cancer, such as Arimidex and Faslodex, have not been studied yet in ovarian cancer.

Agents, such as Lupron, which are commonly used to shut down the ovaries in infertility patients have been reported to have similar effects as Tamoxifen

Lupron is a shot given in the muscle once a month, or once every 3 months

When considering further therapy for recurrent ovarian cancer, it is important to know what side effects and toxicities you have had from previous therapy.

For example, if you had a hard time with lowering of the white blood cell count with previous therapy, choosing a therapy where this is not a major side effect will be safer.

Although there are medications which can help support the white blood cells count, such G-CSF, or Neupogen, there also have side effects to consider

Neuropathy is a side effect that can be cumulative and takes a long time to reverse, so if neuropathy has been a problem for you, therapy that causes further neuropathy should be avoided.

The toxicities listed in the table are those most common to the agents.

Considering quality of life is also important. (link to quality of life section)

If intravenous access has been difficult for you in previous therapies, you might consider a therapy that is less often, or can be given as a pill.

An alternative is to have indwelling IV access, uich as a port-o-cath, subclavian line or long line.

You must consider the potential effects of indwelling catheters on quality of life, which will vary from person to person

If you are having difficulty eating normally, or having nausea or vomiting, taking a treatment that is an oral pill may not be the best choice for you. The treatment only has a chance to work if you can take it and keep it down.

In considering the schedule of a treatment think about

When you have recurrent ovarian cancer, it is always prudent to think about being involved in a clinical trial. Since the available treatments do not work for every patient, or even most patients, new therapies are always being studied.

Clinical trials are designed to answer specific questions about a new treatment, and therefore have very strict rules about who is eligible, or a candidate for the therapy. These rules are there to protect patients from undue harm.

New treatments are first studied in the laboratory by giving the treatment to cancer cells growing on plastic dishes in a tissue culture. If a treatment shows activity there, it is then tested for its effects in at least one type of animal. If the treatment appears active and safe in an animal, it may make it to a clinical trial.

Many treatments are found to be active in animals but do not work in people or are too toxic in people.

Clinical trials are divided into different Phases, depending how far along new treatment is in development. The Phases are I, II and III.

The purpose of a phase I clinical trial is to test if a new treatment is safe to give to people. Or is a new combination of treatments is safe to give together.

Most Phase I clinical trials in cancer are not limited to a single type of cancer, but are for patients for whom no other active therapy is known

A Phase I trial is not to see if a treatment is active in treating cancer

A usual design for a Phase I trial is to treat 3 patients at a chosen low dose of a new treatment for 2 courses of therapy. If none of those patients develops a sever side effect (which are clearly described in the study) then 3 more patients are treated at the next highest dose. This goes on until the "maximum tolerated dose" is found. This is the dose below which sever toxicity occurred.

The purpose of a Phase II clinical trial is to find out if a new treatment is active in a certain disease.

The dose used in a Phase II study, is the maximum tolerated dose defined by a Phase I study

In a Phase II study, all the patients have the same disease, for example, ovarian cancer.

All patients receive the same dose of the treatment and the response rate is determined

The number of patients in a Phase II trial is dependent on what response rate you hope to see. The number is set at the beginning of the study and is usually limited to about 40 patients in ovarian cancer studies.

Response rates are calculated by the percentage of all treated patients who had either a partial or complete response to the treatment for at least 30 days.

The duration of the response is also measured.

For ovarian cancer, a new treatment is considered active if it has at least a 20% response rate with tolerable toxicity and a duration of response that is considered clinically meaningful (usually at least 4 months).

The purpose of a Phase III clinical trial is to test if an active new treatment is better than the existing standard treatment.

In ovarian cancer, Phase III studies are usually only done for patients receiving primary therapy, women with recurrent ovarian cancer.

If the new treatment is better than the standard treatment, it becomes the new standard treatment.

Who is eligible for clinical trials?

There are many clinical trials for women with recurrent ovarian cancer.

Most trials are in the Phase I or II stage

Phase II trials involve treatments that are further along in development.

Phase II trials have strict rules for who can go on the study.

Phase II trials are usually only studying one type of cancer.

Many Phase II studies include women who have only one prior therapy.

Phase I trials are new treatments that are looking at treatment safety.

Phase I studies usually allow any number of prior treatments.

Phase I studies usually include several different cancer types.

All clinical trials have strict rules about who can participate in the study.

These rules are for patient safety and so the study can answer the question it is asking.

For example, if a study wants to answer the question "Is treatment X active in cervical cancer?" Only patients with cervical cancer can participate.

General criteria that are required for participation in most clinical trials are:

1) Normal kidney and liver function

2) Adequate red and white blood cell counts and platelet counts

3) Normal gastrointestinal function- you are eating, drinking and having normal bowel movements

4) Good "performance status"- you are up out of bed and functioning normally at least 50% of the day

5) You have only one type of cancer

Beyond these, all studies have particular rules depending on the type of treatment.

It is important to know that most clinical trials require that all treatment given while on the trial is given at the hospital where the trial is open.

For example, if you live in Kentucky and the clinical trial is open in California, you have to go to California for all your treatment.  This is another quality of life issue to consider

Who does clinical trials and how do I find out about them?

Cooperative groups are large groups consisting of Doctors, from multiple hospitals, cancer centers, and clinics who group together to do trials

The Gynecologic Oncology Group (GOG) is the largest group that studies ovarian cancer

The Southwest Oncology Group also does ovarian cancer studies

Most large academic hospitals also have some trials of their own

This includes the National Cancer Institute and major cancer centers

Although doctors in private practice generally do not design their own studies, they often participate in cooperative group trials or trials sponsored by Pharmaceutical companies

Ask you doctor if they are involved with any studies.

Cooperative groups and most large academic centers have internet websites to help you find clinical trials

Things to remember when considering a clinical trial:

1) Make sure a trial is open and you are potentially eligible before traveling to a new doctor

2) Realize that once you get there, you still may not be eligible

3) Decide before you go if you would be willing to consider treatment at a distance from home

4) Find out if the trial pays for the new treatment and any medical expenses incurred; if not will your insurance pay for it?

5) If you consider joining a trial, as how many patients have been treated so far, and what has been the outcome

How well has the treatment been tolerated?

Has it shown any activity so far?

Quality of life issues

Since treatment of recurrent ovarian cancer is meant to extend life and not cure the disease in most women, it is of utmost importance for you to consider what is quality life for you in deciding on therapy.

Think about what you will and will not suffer to try to extend the quantity of your life.

This is different for each individual and may change over the course of your illness.

This is decision that your doctor cannot make for you.

Discuss what is important to you with your family or close friends and with your doctor, so everyone who cares for you understands what is important to you.

The FREE Patient Active Guide to Living With Ovarian Cancer explores new ways to improve a person’s quality of life during and after treatment, by discussing ways to be proactive about fighting the disease. It is The Wellness Community’s hope that this guide and accompanying workshops will help people with cancer strategize with their physician about treatment options and identify valuable support services that can make a difference in the fight for recovery.

· download free at our website: by clicking here

· call to request a free copy from The Wellness Community at 1888-793-WELL

· email to request a free copy at: help@thewellnesscommunity.org