What is the treatment for ovarian cancer?
Epithelial ovarian cancer treatment most often consists of surgery and chemotherapy. The order is best determined by a gynecologic oncologist.
Surgery consists of an effort to remove all visible disease in the abdomen, commonly called surgical debulking. If one imagines a handful of wet sand thrown on the ground, you will see small piles and bigger piles. This is often how the abdomen looks when in surgery. It is the job of the surgeon to remove, (also known as debulking) as many of these masses as possible. This surgery usually results in removal of both tubes and ovaries, the uterus (hysterectomy), removal of the omentum (omentectomy -- a large fat pad that hangs off of the colon), lymph node biopsies and any other organ involved in the disease. This can mean a portion of the small bowel, large bowel, liver, the spleen, the gallbladder, a portion of the stomach, a portion of the diaphragm, and removal of a portion of the peritoneum (a thin lining in the abdomen that covers many of the organs and the inside of the abdominal wall). Done properly, this can be a very extensive surgery. The patients who live the longest have all of the visible nodules taken out at time of surgery. To accomplish an “optimal debulking,” at minimum, no individual nodule greater than 1 cm should be left behind. If this cannot be done, the patient is brought back to the operating room for a second surgery after a few rounds of chemotherapy (neoadjuvant chemotherapy and interval debulking surgery).
It should be noted that now many gynecologic oncologists believe that “optimal debulking” should mean that there is no visible disease left at the time of surgery. This has been a shift over the last years. Historically the goal was to leave no individual nodule greater than 2 cm behind. This has steadily progressed to the point where the term “optimal debulking” is now accepted by many to mean that there is no disease left to remove. As we have progressed to this point, surgery has become more involved, on a more routine basis. This has led to a concern about undertreatment of elderly patients due to a fear that they cannot survive the surgical risks.
There has recently been new research indicating that if all visible disease cannot be removed at the time of surgery, that giving chemotherapy for three cycles before surgery may be just as beneficial as up front surgery. When this is done, the amount of surgery needed to optimally debulk a patient is significantly less. This is a concept that has been used historically, but it was always felt to be substandard. With recent research as well as ongoing research, more information is coming out that supports the use of this strategy in some circumstances.
Any patient healthy enough to tolerate chemotherapy will often benefit greatly from its use. The drugs used in ovarian cancer tend to have fewer side effects, and thus are easier to tolerate than many other chemotherapy drugs. Currently, there are two ways to give chemotherapy in ovarian cancer. Traditionally, it is given into the vein intravenously (IV). When initially diagnosed, the two most common drugs are carboplatin and paclitaxel (Taxol). Most commonly, the carboplatin is given every 21 days and the paclitaxel is given every 21 days, or every 7 days.
Another way of giving the chemotherapy is to place it directly into the abdomen (intraperitoneal or IP). In many studies, intraperitoneal administration has been shown to significantly increase survival. This is most often used after optimal surgical debulking. Currently the drugs used are cisplatin and paclitaxel. In a 21 day cycle, the paclitaxel is given IV on day 1, followed by cisplatin IP on day 2, and paclitaxel IP on day 8. This regimen is the current standard in IP ovarian cancer chemotherapy. There are studies that are looking at substituting carboplatin for the cisplatin, because the side effects are less. We do not have an answer for this yet.
The drug bevacizumab has also been used experimentally in the initial treatment of ovarian cancer. When used in the initial rounds of chemotherapy and then used for 12 months after the initial six cycles of chemotherapy, there is research indicating that the cancer, if not cured, will come back at a later date than would be expected with traditional chemotherapy regimens (increased progression-free survival). This has not yet been shown to increase survival however. Bevacizumab is a very good drug to use in ovarian cancer; however, the timing of its use is still being determined.
Some centers are starting to experiment with heated intraperitoneal chemotherapy (HIPEC). However, at this time, HIPEC is still experimental. There are significant risks and complications from surgery with HIPEC, and it has not yet been shown to extend survival over standard chemotherapy. Until a trial is done proving its usefulness, HIPEC should be used with caution.
Maintenance chemotherapy is a concept that gives long-term chemotherapy, often for a year, of a single drug. The idea is that, if the patient is not cured, then this may prevent the recurrence from occurring for an extended amount of time. Drugs that have been studied with this approach include paclitaxel and bevacizumab. We have yet to show an increased survival using this method of treatment. This creates controversy, because if the patient will not live longer, then why subject them to 12 months of chemotherapy? As of now, there is no definitive answer on whether or not this should be done. Each patient can discuss this with her treating physician to get information.
When epithelial ovarian cancer recurs, the timing of the recurrence dictates how it is treated. Sometimes, a patient may be a good candidate for surgery again. If not, then chemotherapy is used. The type of drugs used are determined by how long it has been since the last time a patient has taken a drug containing platinum (carboplatin or cisplatin). If it has been less than 6 months, then the patient is termed platinum resistant. If it has been more than 6 months since the last day of platinum-based chemotherapy, then often a platinum-containing drug will be used again.
If the patient is still platinum sensitive, then often she will receive a platinum drug with another drug. This can be paclitaxel again, or another taxane type drug, such as docetaxel. Also, another class of drugs, such as gemcitabine or pegylated liposomal doxorubicin (PLD) may be used. Often the combination is chosen based on how a patient tolerated her previous chemotherapy, as well as the side effect profile that will best suit the patient. If the patient is platinum resistant, then often a single drug is used. These can include drugs that have previously been used. Agents used include pegylated liposomal doxorubicin, docetaxel, paclitaxel, topotecan, gemcitabine, etoposide, and bevacizumab. The order, schedule and dosing are quite variable, depending on many factors.
The Gynecologic Oncology Group is a national organization that sponsors clinical trials in gynecologic cancers. Patients can ask their physician if they are eligible for a trial that may help them, as this is how new drugs are discovered. If a doctor or hospital does not participate in the GOG trials, a doctor can often contact a regional center that does.
Stromal and germ cell ovarian tumors are most often treated with a combination of bleomycin, etoposide, and cisplatin. There is much less research on these as they are more curable and much less common than epithelial tumors. Because of their rarity, it will be very difficult to find effective new treatments.