Ovarian cancer occurs most frequently in women ages 40 to 65. The lifetime risk is low at 1.4 to 1.8 percent (one in 75 women) in the United States. There are several types of cancer arising in the ovary, although epithelial ovarian cancer is the most common, and is the subject of this review.

Treatment of newly diagnosed ovarian cancer- The treatment focuses on eliminating cancerous tissue and preventing the disease from coming back (recurring).

Surgery – The first step in treating ovarian cancer usually involves surgical removal of as much cancerous tissue as possible (called optimal surgical debulking or optimal cytoreduction). This procedure improves the woman’s outcome or prognosis and it may also influence the choice of chemotherapy treatment. The initial surgery is ideally performed by a gynecologic oncologist or a gynecologist with experience in surgical treatment of cancers of the female reproductive system.

The stage of the cancer is determined accurately at the time of surgery. Additional imaging studies (CT scan of abdomen and pelvis and chest x-ray) are also required to exclude cancer spread to the lungs or liver. Further prognosis and treatment recommendations are determined after the pathologic information from surgery is available.

Chemotherapy – The need for chemotherapy after surgery depends on the stage of the disease. For selected women with stage IA and IB disease surgery alone is effective in treating the disease, no additional therapy is recommended. In almost all other cases, chemotherapy is recommended in conjunction with surgery.

What is chemotherapy? – Chemotherapy refers to the use of medicines to stop or slow the growth of cancer cells. Most chemotherapy drugs are given by vein. A newer treatment strategy for women with optimally debulked stage III ovarian cancer involves giving chemotherapy directly into the abdominal (peritoneal) cavity. This is called intraperitoneal or IP chemotherapy and is discussed below.

Neoadjuvant chemotherapy – In most cases, chemotherapy is given after surgery for ovarian cancer. Occasionally, it is too risky to perform initial surgery because of the extensive nature of the cancer and/or the debilitated condition of the patient. Neoadjuvant chemotherapy is a reasonable approach for women who could not tolerate a lengthy operation and recovery period. The hope is that chemotherapy will shrink the tumor and improve the chances for a later debulking surgery.

The disease stage influences the chemotherapy recommendation

Stage I disease – After surgery, women with stage IA or IB ovarian cancers that appear to be fairly nonaggressive (grade 1) do well without chemotherapy, and observation alone is a standard approach. In contrast, women with higher grade (grade 2 or 3), stage IA or IB and all women with stage IC ovarian cancers are advised to have adjuvant chemotherapy. The standard regimen includes a platinum-based combination such as paclitaxel and carboplatin.

Stage II – Women with stage II disease have a prognosis that is slightly worse than those with stage I disease. Many groups suggest the use of six cycles of intravenous paclitaxel and carboplatin, similar to the regimen used for women with stage III/IV disease.

Stage III to IV disease – In the United States, the standard course of chemotherapy after surgical debulking includes six cycles of intravenous paclitaxel and carboplatin, each cycle given every 3 weeks with treatment beginning two to six weeks after surgery. Women with optimally debulked disease should also consider the use of intraperitoneal chemotherapy as a component of their chemotherapy. The preferred treatment for all patients is enrollment in a clinical trial.

Intraperitoneal chemotherapy – Opposite to almost all other cancers, ovarian cancer typically does not spread through the bloodstream. Instead, tumor growth is often limited to the abdominal (peritoneal) cavity, even in advanced cases. Administration of chemotherapy directly in the abdominal cavity is called intraperitoneal or IP chemotherapy. The advantage of IP therapy compared to the intravenous (IV) route is that higher doses of the drugs can be given directly to the areas at highest risk for tumor involvement.

IP chemotherapy is administered through a small, soft, flexible catheter, which is surgically placed in the peritoneal cavity either at the time of surgical debulking or as a separate procedure. The catheter can be left in place several months at a time. A website with educational materials about intraperitoneal catheters and IP chemotherapy is available for the Gynecologic Oncology Group (www.gog.org/IPChemoEd/ipchemoed.html).

Benefits – In a large randomized clinical trial, women with optimally debulked stage III disease who were treated with IP chemotherapy had a 16 month longer survival as compared to women who were given all their chemotherapy IV, even though most of the women did not take the entire six courses of IP treatment because of side effects.

Risks – These include both catheter-related complications (infection, blockage or leakage of the catheter) as well as non-catheter related problems (low white and red blood cells, nausea, vomiting, abdominal pain, and neurologic side effects such as numbness and tingling of the fingers and toes).

Recommendation for IP chemotherapy – The National Cancer Institute recommends that IP chemotherapy be strongly considered for women with stage III ovarian cancer who are left with a small amount of tumor after optimal debulking. However, at least for the present, a standard regimen of intravenous paclitaxel plus carboplatin is an acceptable alternative to IP therapy because of toxicity issues.

Maintenance or consolidation chemotherapy – The value of “maintenance” chemotherapy after the woman achieves a complete response to first-line chemotherapy has been debated. In two clinical trials, women who were given additional chemotherapy did not live longer then the ones who were observed. The side effects of chemotherapy were significant, also. In view of these results, the use of maintenance chemotherapy is not common, although the concept of improved overall survival is being tested in a clinical trial (GOG 212).

Second-line treatment – is reserved for women who’s disease recurs following a complete response or do not respond to the initial chemotherapy. The choice of chemotherapy agents for second-line treatment is determined by the disease free interval. If the woman had a complete response to the initial treatment (paclitaxel and either carboplatin or cisplatin) and the response lasted longer than 6 months she can be treated with the same agents. Alternatively, a regimen including gemcitabine and carboplatin may be used, especially in women who have significant residual nerve damage (peripheral neuropathy) from the original regimen.

If the women did not respond well to the first line therapy or the disease recurred within 6 months of completing such therapy, a different non-platinum containing regimen may be considered. A single drug rather than combination therapy is recommended in these cases. Liposomal doxorubicin, topotecan, docetaxel, oral etoposide, gemcitabine, vinorelbine, ifosfamide, leucovorin modulated 5-fluorouracil, or tamoxifen are a variety of drugs that may be considered.

Molecularly targeted therapy – may be of benefit for second-line therapy. The drug bevacizumab (Avastin) interacts with a protein called vascular endothelial growth factor (VEGF) involved in the development of blood supply within a growing cancer; this blood supply is essential for the tumor to grow and spread. Bevacizumab also enhances the antitumor effect of conventional chemotherapy drugs, and is used in combination chemotherapy regimens for the treatment of other advanced tumors, such as colorectal, lung, and breast cancer.

Bevacizumab is effective for the treatment of ovarian cancer, and it may be considered for women with platinum resistant ovarian cancer, either alone or in combination with chemotherapy. The drug is not yet approved by the Food and Drug Administration and it is only available in the context of research clinical trials. A major side effect of the drug is the risk of bowel perforation during treatment, especially in patients with preexisting tumor of the gastrointestinal tract (e.g., bowel obstruction or bowel wall thickening). However, the overall risk is estimated to be 7% or less.

Timing of second-line therapy – An area of major controversy is the optimal timing of second-line therapy. Immediate treatment is reasonable for women who have symptoms related to the disease recurrence, with the specific goal of palliation (improvement) of the tumor-related symptoms. In contrast, the optimal timing of second-line therapy in women who are asymptomatic, but who have either a rising blood level of the tumor marker CA 125 or an abnormal CT scan, is uncertain. Since second-line therapy is unlikely to result in a cure, some experts advise waiting until symptoms develop. Others argue that women with smaller volume of disease have a higher chance to respond to therapy, especially if the time between stopping the initial chemotherapy and disease recurrence is longer than 24 months.

Surgery – Surgery may be beneficial to women with recurrent disease if the tissue can be easily removed and the woman has been free of disease for more than 6 to 12 months. This could also alleviate discomfort caused by the growth of the tumor.

Post treatment surveillance – To monitor for the possibility of recurrent ovarian cancer, follow-up blood tests, physical examinations and imaging tests are recommended for at least five years after treatment ends. The guidelines from the National Comprehensive Cancer Network (NCCN) are as follows:

• Office visits every two to four months for two years, then every six months for three years, then annually.
• A blood test for CA 125 at every visit
• Pelvic examination, chest X-ray, and CT scans of abdomen and pelvis if there are any abnormalities on the blood test of examination. About 1 in 5 ovarian cancers cannot be reliably followed with CA 125 levels since they do not produce excess CA 125. These patients are best served with regular imaging studies at same intervals as physical examinations.

Signs of recurrence – Even women who have a complete response to initial therapy can have a recurrence of ovarian cancer at a later time. The higher the stage at original diagnosis the higher the risk of recurrence. Signs of recurrent ovarian cancer include symptoms of abdominal bloating, food intolerance, constipation alternating with diarrhea, abdominal pain, nausea, vomiting, back pain; rising CA 125 levels or new abnormalities on a follow up CT scan. The recommendation for treatment depends on the presence of symptoms and extent of disease. A rising CA 125 in the absence of symptoms and presence of normal imaging studies does not warrant immediate treatment.

Clinical trials – A clinical trial is a carefully controlled way to study the effectiveness of new treatments or new combinations of known therapies. Below are more resources about clinical trials:

www.cancer.gov/clinical_trials/learing/

www.cancer.gov/clinical_trials/

http://clincaltrials.gov/

Where to get more information – Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable.

American Society of Clinical Oncology
www.cancer.net/portal/site/patient

The Women’s Cancer Network
www.wcn.org

National Comprehensive Cancer Network
www.nccn.org/patients_gls.asp

Gynecologic Oncology Group
www.gog.org/gynecologiccancerinformation.html

National Cancer Institute
1-800-4-CANCER
www.cancer.gov

American Cancer Society
1-800-ACS-2345
www.cancer.org

National Ovarian Cancer Coalition
www.ovarian.org