Medications:

Following surgery, patients (other than those with early-stage, low-grade disease) usually have chemotherapy. Unlike surgery and radiation, which treat the cancerous tumor and the area surrounding it, drug therapy destroys rapidly dividing cells throughout the body, so it is a systemic therapy.

Ovarian cancers are very sensitive to chemotherapy and often respond well initially. Unfortunately, in most cases, ovarian cancer recurs. With treatment advances, however, more than half of women now survive 5 years or longer. Doctors are now approaching this disease as a chronic and potentially long-term illness that requires the following:

• Identifying the disease recurrence as soon as possible
• Administering treatments that are as effective as possible without causing suffering
• Partnering with the patient in determining her own best course

Drugs Used in Chemotherapy

Standard Chemotherapy. The standard initial chemotherapy uses a combination of:

• A platinum-based drug, such as carboplatin (Paraplatin) or cisplatin (Platinol). Carboplatin is preferred over cisplatin in the combination. Carboplatin works as well as cisplatin but is less toxic and can be administered in a more convenient, outpatient regimen.
• A taxane, such as paclitaxel (Taxol) or docetaxel (Taxotere). Currently paclitaxel is the drug most often used as initial therapy in combination with a platinum drug.

Chemotherapy for Relapsed or Refractory Cancer. Unfortunately, even in patients who respond, the disease eventually becomes resistant to the first-line drugs, and the cancer returns. Some ovarian tumors are resistant to platinum drugs.

Once cancer recurs or continues to progress, the patient may be treated with more cycles of carboplatin and a taxane drug, or a different type of chemotherapy drug may be used in combination treatment.

In 2006, gemcitabine (Gemzar) was approved as a treatment for recurrent ovarian cancer. It is used in combination with carboplatin for women with advanced ovarian cancer that has relapsed at least 6 months after initial therapy. Other drugs used for recurrent ovarian cancer include doxorubicin (Adriamycin, Doxil), etoposide (Vepesid), and vinorelbine (Navelbine).

Hormonal therapy is also an option for patients who cannot tolerate or who have not been helped by chemotherapy. Hormonal therapy drugs include tamoxifen (Nolvadex), and aromatase inhibitors such as letrozole (Femara), anastrozole (Arimidex), and exemestane (Aromasin).

Administration of Chemotherapy

In general, the typical initial chemotherapy regimen is:

• Paclitaxel and carboplatin are administered in an outpatient clinic within several weeks of the surgery.
• Each treatment takes about 4 - 5 hours to complete.
• It is repeated every 3 weeks for a total of six times. (Each 3-week interval is known as a cycle of chemotherapy.)

Chemotherapy is either administered intravenously (by vein) or intraperitoneally (through the abdominal cavity). Recent research has indicated that patients with stage III ovarian cancer who receive intraperitoneal chemotherapy have a significant survival advantage compared with patients who receive standard intravenous chemotherapy. However, intraperitoneal chemotherapy can cause more severe side effects, including abdominal pain and bowel damage. Some patients cannot tolerate intraperiotenal chemotherapy. Intraperitoneal chemotherapy requires careful catheter insertion and maintenance, and doctors need to be well trained to perform this procedure.

Side Effects of Chemotherapy

Side effects occur with all chemotherapeutic drugs. They are more severe with higher doses and increase over the course of treatment. Some may be long-lasting. In one study of ovarian cancer survivors, 20% had long-term treatment side effects, such as gynecologic and abdominal problems. Even so, most enjoyed a high quality of life that was comparable to other cancer survivors and peers without a history of cancer.

Common side effects include:

• Nausea and vomiting. Drugs known as serotonin antagonists, especially ondansetron (Zofran), can relieve these side effects in nearly all patients given moderate drugs and most patients who take more powerful drugs.
• Diarrhea
• Temporary hair loss
• Weight loss
• Fatigue
• Depression

Serious short- and long-term complications can also occur and may vary depending on the specific drugs used. The following list includes some of these complications and a few of their treatments:

• Anemia
• Increased chance for infection from severe reduction in white blood cells (neutropenia)
• Abnormal bleeding (thrombocytopenia)
• Problems with concentration, motor function, and memory

Follow-Up Recommendations

After surgery and chemotherapy, patients should have a physical exam (including pelvic exam) every 2 - 4 months for the first 2 years, followed by every 6 months for 3 years, and then annually. A CA-125 blood test should be measured at each visit if the level was initially elevated. Falling CA-125 levels indicate effective treatment while persistently elevated levels indicate resistance to the chemotherapy. Your doctor may also order a computed tomography (CT) scan of your chest, abdominal, and pelvic areas and a chest x-ray. If your family history suggests a genetic component, genetic counseling may be recommended.

Investigational Drugs

Any patient with ovarian cancer is a candidate for clinical trials. In addition to testing high-dose or combinations of chemotherapy, biologic drugs with unique actions are being investigated. These drugs are primarily being studied for treatment of advanced or recurrent ovarian cancer, in combination with standard chemotherapy drugs. Promising biologic drug treatments for ovarian cancer include:

• Bevacizumab (Avastin) targets vascular endothelial growth factor (VEGF), a protein involvedin cancer cell growth. It is being studied extensively for treatment of advanced and recurrent ovarian cancer.
• Phenoxodiol is a multiple signal transduction regulator that is being developed as a broad-spectrum anti-cancer drug, and is being studied for its ability to shrink tumors or stop tumor growth in women with ovarian or fallopian cancer who have failed other forms of chemotherapy.
• Pertuzumab (Omnitarg) is the first of a new class of drugs called HER dimerization inhibitors. It is designed to inhibit tumor growth for tumors that express the HER2 receptor protein. It is being investigated in combination with gemcitabine for women with platinum-resistant ovarian, peritoneal, or fallopian cancer.
• Ixabepilone and other epithelone drugs are being studied for ovarian cacner. Epothilones are a new class of anti-cancer drugs that are similar to taxanes (paclitaxel) but are more potent.