Treatment of Recurrent Ovarian Cancer

Patients who have been diagnosed with ovarian cancer may have persistent, refractory or recurrent cancer following treatment with surgery and first-line chemotherapy. Persistent cancer refers to residual cancer growths or cells that persist during and following initial treatment.

Patients who have achieved complete remission following initial therapy and who subsequently experience a return of cancer cells after treatment are said to have relapsed or recurrent cancer. Patients with ovarian cancer who experience progression or continued growth of the cancer during treatment are said to have refractory cancer. Patients with persistent, recurrent or refractory ovarian cancer can benefit from additional treatment with second-line therapy, which is often referred to as salvage therapy. A patient's treatment options will differ depending on whether the cancer is persistent, recurrent, or refractory.

Recurrent or persistent ovarian cancer may be detected by several methods.

• Some patients will experience abdominal swelling, pain or symptoms related to the spread of cancer cells (metastases) to the bone, liver, or brain.
• Other patients may simply have an increase or persistent elevation in the CA-125 level, a blood test commonly used to monitor ovarian cancer activity.

When an increase in the CA-125 occurs, most patients will undergo ultrasound or CT scanning of the abdomen and pelvis or other diagnostic procedures in order to determine the location of recurrent cancer. The availability and effectiveness of additional treatment depends on the kind of chemotherapy previously administered, the duration since last treatment, and the extent of recurrent cancer.

Despite recent improvements, initial or first-line chemotherapy fails to produce a remission in more than 70 percent of patients with ovarian cancer. Furthermore, approximately 40 to 50 percent of the women who do achieve a remission after first-line chemotherapy will experience a recurrence of cancer within three years.

Patients who have failed initial surgery and first-line chemotherapy for ovarian cancer are broadly divided into three groups:

1. Persistent ovarian cancer
2. Recurrent ovarian cancer
3. Refractory ovarian cancer

Treatment of Persistent Ovarian Cancer

Patients with persistent ovarian cancer have cancer cells that are detected after initial surgery and first-line chemotherapy. Persistent ovarian cancer is detected either by an elevated CA-125 blood level, abnormal x-rays and CT scans, or with a biopsy performed during second-look laparotomy.

Individuals with persistent ovarian cancer following first-line chemotherapy have a number of treatment options. Additional debulking surgery to remove as much persistent cancer as possible may be considered before resuming further treatment. Further treatment is still necessary since undetectable microscopic deposits of cancer can still exist and cause recurrences even after successful debulking surgery.

Patients may elect to receive treatment with additional standard chemotherapy; however, some doctors feel that patients with persistent cancer should receive a different treatment or consider participation in a clinical trial.

Continued standard chemotherapy - The standard course of initial chemotherapy is approximately six cycles, or about four months of treatment. If, after six cycles, there is a small amount of persistent cancer, some doctors feel further chemotherapy treatment for 10 or 12 cycles may continue to cause shrinkage of the cancer. Some patients may achieve a complete remission with continued standard chemotherapy.

Second-line chemotherapy - Not all patients are able to undergo secondary debulking surgery or are expected to improve with continued treatment with a first-line chemotherapy regimen. Salvage or second-line chemotherapy with other anti-cancer drugs that destroy cancer cells by a different mechanism may provide additional benefit over the continuation of first-line chemotherapy.

Treatment of Recurrent Ovarian Cancer

Patients with recurrent ovarian cancer have experienced a period of "remission" following initial surgery and first-line chemotherapy, but have subsequently developed a cancer recurrence. Both the effectiveness and type of available therapy depends on the first-line chemotherapy received, the length of time since finishing treatment, and the extent of recurrent cancer.

In general, salvage chemotherapy treatment is used to improve a patient’s quality of life by reducing symptoms of recurrent cancer. Certain patients can derive significant benefit from additional treatment. Salvage chemotherapy is typically associated with lower response rates and a shorter duration of remission than first-line chemotherapy.

• The average duration of survival after recurrence of ovarian cancer is about 12 to 18 months.
• Fewer than 1 in 10 patients survive beyond 5 years following standard salvage chemotherapy treatment.

The length of time between the completion of first-line chemotherapy and the development of recurrent cancer affects treatment options.

• Patients who develop recurrent cancer more than 6 months after first-line chemotherapy can experience another remission following treatment with the identical first-line chemotherapy that was previously used.
• Patients who develop recurrent cancer within 6 months from first-line chemotherapy are less likely to improve with the same anti-cancer drugs and should consider treatment with a different chemotherapy regimen.

All patients with recurrent cancer should also consider participating in clinical trials.

Recurrence after 6 Months from Therapy

Patients who develop recurrent cancer more than six months after first-line chemotherapy or have not been treated with platinum and taxane chemotherapy have a good chance of improving with these drugs. Debulking surgery to remove as much cancer as possible may be considered before resuming chemotherapy treatment.

The length of time between the completion of first-line chemotherapy and the development of recurrent disease can help determine whether additional treatment with a taxane and platinum will be effective in shrinking recurrent cancers. Over half of patients who develop a recurrence longer than 12 months from initial treatment are likely to improve with further chemotherapy, compared with less than half of patients who develop a recurrence between six and 12 months from initial treatment.

Not all patients will improve following re-treatment with taxane and platinum chemotherapy. Some patients are also unable to receive these anticancer drugs due to limiting side effects. Patients unlikely to benefit are typically offered salvage or second-line chemotherapy with one or more of many available anticancer drugs. They may also consider participating in a clinical trial.

Recurrence within 6 Months from Therapy

Patients who develop recurrent cancer within six months from first-line therapy are less likely to improve with additional treatment that uses the same first-line chemotherapy drugs. In general, patients with recurrent ovarian cancer that occurs shortly after initial therapy have few standard treatment options.

Most patients will have already received taxane and platinum chemotherapy, and are considered resistant to these drugs. Certain patients can derive significant benefit from additional treatment with salvage or second-line chemotherapy or from participation in a clinical trial designed to evaluate promising new treatment strategies.

Treatment with Salvage Chemotherapy

A number of newer chemotherapy drugs have demonstrated an ability to kill cancer cells even when first-line chemotherapy is ineffective. Salvage chemotherapy may consist of single chemotherapy drugs or combinations of anticancer therapies. When one chemotherapy drug stops killing cancer cells, sometimes switching to a different anticancer drug is effective. In general, the chances of remission become smaller and smaller as drugs are changed, yet the potential side effects continue to increase with each new drug.

Doxil^® (doxorubicin) - By packaging the anticancer drug doxorubicin in tiny liposomes, the drug is less likely to be broken down by the body and is more likely to reach cancer cells. A number of clinical studies have evaluated the use of doxorubicin in patients who are resistant to paclitaxel and Platinol chemotherapy. Doxil has been directly compared to Hycamtin and found to have equivalent or improved survival with fewer side effects than Hycamtin

Gemzar^® (gemcitabine) - Gemzar has demonstrated significant anticancer activity in patients who are resistant to taxanes and platinum chemotherapy. Gemzar appears to have similar anticancer activity to Doxil and Hycamtin, but may be associated with fewer side effects. Additionally, the combination of Gemzar and Platinol appears to kill more cancer cells than each drug given alone. Doctors have reported that the combination has produced a partial or complete disappearance of cancer in 69 percent of patients.

Etoposide: Etoposide is an anticancer drug that can be taken orally. In a clinical trial conducted by the Gynecologic Oncology Group, more than 25 percent of patients whose cancer was resistant to Platinol experienced a remission following treatment with etoposide.

Hycamtin^® (topotecan) - A number of clinical studies have evaluated the use of Hycamtin in patients who are resistant to Platinol. About 14 percent of Platinol resistant patients achieved remission following treatment with Hycamtin, indicating that it might be an effective treatment option for these patients.

In a clinical study conducted in Europe, Hycamtin was directly compared with paclitaxel in patients who were resistant to Platinol.

• Hycamtin was at least as effective as paclitaxel for killing cancer cells and producing cancer shrinkage.
• Over half of the patients who received Hycamtin survived at least one year from the start of the clinical trial.

Research is in progress to refine existing treatments and develop new ones. For information on some of the techniques currently under investigation, see Strategies to Improve Treatment.