Stage IV Ovarian Cancer
Patients diagnosed with Stage IV or metastatic ovarian cancer have disease that has spread outside the abdomen or into the liver.
A variety of factors ultimately influence a patient’s decision to receive treatment of cancer. The purpose of receiving cancer treatment may be to improve symptoms through local control of the cancer, increase a patient’s chance of cure, or prolong a patient’s survival. The potential benefits of receiving cancer treatment must be carefully balanced with the potential risks of receiving cancer treatment.
The following is a general overview of the treatment of Stage IV ovarian cancer. Circumstances unique to your situation and prognostic factors of your cancer may ultimately influence how these general treatment principles are applied. The information on this Web site is intended to help educate you about your treatment options and to facilitate a mutual or shared decision-making process with your treating cancer physician.
Most new treatments are developed in clinical trials. Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies. The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Participation in a clinical trial may offer access to better treatments and advance the existing knowledge about treatment of this cancer. Clinical trials are available for most stages of cancer. Patients who are interested in participating in a clinical trial should discuss the risks and benefits of clinical trials with their physician. To ensure that you are receiving the optimal treatment of your cancer, it is important to stay informed and follow the cancer news in order to learn about new treatments and the results of clinical trials.
Currently, the standard treatment for Stage IV ovarian cancer consists of both surgery and chemotherapy. Unfortunately, less than 10% of patients experience long-term survival following standard treatment. This is because Stage IV ovarian cancer is difficult to completely remove with surgery and the currently available chemotherapy is unable to eradiate all of the remaining cancer. Both optimal cytoreductive surgery and platinum-based chemotherapy prolong the time to cancer recurrence and improve overall survival.
During cytoreductive surgery, physicians attempt to remove as much of the ovarian cancer as possible. Cytoreductive surgery is beneficial because it reduces the number of cancer cells that ultimately need to be destroyed by chemotherapy and therefore, decreases the likelihood of the cancer developing a resistance to chemotherapy. Initial cytoreductive surgery in ovarian cancer is currently considered the standard of care because clinical studies have shown that patients who have had optimal cytoreductive surgery live longer and have a more prolonged time to cancer recurrence than patients who have had suboptimal cytoreductive surgery.1
Following cytoreductive surgery, all patients with Stage IV ovarian cancer are offered additional treatment. This is because the majority of patients will experience recurrence of their cancer even after complete surgical resection. Nearly all patients with Stage IV disease have cancer that was not removed by surgery. An effective treatment is needed to eliminate the remaining cancer in order to improve the outcome achieved with surgical removal of the cancer. Currently, this treatment is chemotherapy.
Chemotherapy for Stage IV Ovarian Cancer
Clinical trials have demonstrated that for patients with advanced ovarian cancer, treatment with combination chemotherapy regimens containing a platinum (Platinol® or Paraplatin®) compound prolongs the duration of survival and prevents more recurrences of cancer compared to treatment with surgery and non-platinum compounds. Chemotherapy typically consists of paclitaxel and a platinum compound administered every 3 weeks for 6-8 cycles.
Chemotherapy is most often given after surgery. In some cases, however, it may be given both before and after surgery. Giving chemotherapy before surgery may reduce the amount of cancer, thereby allowing for more complete surgical removal of the cancer. This approach to treatment remains controversial, but it may be considered for selected patients with advanced disease who do not appear to be candidates for initial surgery.2
Unfortunately, fewer than 10% of patients treated with a platinum compound and paclitaxel survive without evidence of cancer recurrence 5 years following treatment. Because many patients still experience recurrence of their cancer following standard therapy, some patients and their doctors consider participation in clinical trials evaluating new treatment approaches as their initial option.
Strategies to Improve Treatment
The progress that has been made in the treatment of ovarian cancer has resulted from improved development of chemotherapy treatments and doctor and patient participation in clinical studies. Future progress in the treatment of ovarian cancer will result from continued participation in appropriate studies. Currently, there are several areas of active exploration aimed at improving the treatment of Stage IV ovarian cancer.
Targeted Therapy: Targeted therapies are anticancer drugs that interfere with specific pathways involved in cancer cell growth or survival. Some targeted therapies block growth signals from reaching cancer cells; others reduce the blood supply to cancer cells; and still others stimulate the immune system to recognize and attack the cancer cell. Depending on the specific “target”, targeted therapies may slow cancer cell growth or increase cancer cell death. Targeted therapies may be used in combination with other cancer treatments such as conventional chemotherapy.
A targeted therapy that is showing promise in the treatment of ovarian cancer is Avastin® (bevacizumab).3 Avastin slows or prevents the growth of new blood vessels by inhibiting a protein known as VEGF; this deprives the cancer of oxygen and nutrients. Due to its effects on blood vessels, Avastin may also improve the delivery of chemotherapy to the cancer.
Consolidation Therapy: Consolidation therapy, also called maintenance therapy, refers to extra chemotherapy that is given after completion of standard chemotherapy.4 Consolidation therapy is currently being explored in clinical trials; a question of interest is whether the survival benefit (if any) will outweigh the side effects that accompany prolonged treatment.
Intraperitoneal (IP) Chemotherapy: This treatment approach delivers chemotherapy directly into the abdominal cavity, where there is the greatest number of cancer cells. The chemotherapy is administered through a large catheter that is placed into the abdomen during the surgery to remove the cancer. This treatment appears to be most effective if surgery or other therapy has already reduced the size of any remaining cancer deposits to less than 1 cm, or about half inch (this is often referred to as “optimally debulked”).
Among women with optimally debulked Stage III ovarian cancer, a phase III clinical trial compared treatment with intravenous (IV) chemotherapy alone to treatment with both IV and IP chemotherapy. Women who received both IV and IP chemotherapy survived more than a year longer than women who received only IV chemotherapy, but also experienced more severe side effects.5
Dose-Dense Treatment: Rapid administration of several different single chemotherapy compounds at the maximum tolerated dose allows higher doses of chemotherapy to be delivered and may prevent cancer cells from developing chemotherapy resistance.
Because dose-dense treatment can cause severed side effects, time-staggered delivery of the chemotherapy agents may decrease the risk of side effects caused by combination chemotherapy, while maintaining optimal anti-cancer effects. One recent clinical trial evaluated a treatment regimen that involved 3 chemotherapy agents delivered in a time-staggered manner for patients with advanced ovarian cancer. The regimen consisted of 4 courses of Platinol® and Hycamtin® followed by 4 courses of Platinol® and paclitaxel. (Patients underwent surgery prior to chemotherapy or in between courses.) Nearly 80% of the women in this trial achieved a complete or partial disappearance of their cancer following treatment. This treatment was generally well tolerated; however, there was one treatment related death.
High-Dose Chemotherapy and Autologous Stem Cell Transplant: Chemotherapy targets and kills rapidly dividing cells such as cancer cells. High- dose chemotherapy (HDC) kills more cancer cells than lower-dose conventional chemotherapy. Unfortunately, HDC also kills more normal cells, especially the blood-producing stem cells in the bone marrow. Stem cells are immature cells produced in the bone marrow, which is the spongy material inside bones. Stem cells eventually become either red blood cells, which provide oxygen to tissues, white blood cells, which fight infection; or platelets, which aid in blood clotting.
HDC destroys cancer as well as bone marrow stem cells. When bone marrow is destroyed, stem cell stores are depleted, which leads to low levels of circulating blood cells. When these cells reach critically low levels, complications such as anemia, infection and bleeding can occur. As these complications could result in death, it is imperative to restore stem cell levels as quickly as possible. Stem cell transplantation is an attempt to restore the blood-producing stem cells after HDC has reduced them to dangerously low levels. In autologous stem cell transplantation, the patient’s own stem cells are collected before chemotherapy treatment, frozen, and infused back into the patient after treatment to “rescue” the bone marrow.
Researchers from the Autologous Blood and Marrow Transplant Registry evaluated over 400 women with advanced ovarian cancer who received HDC and autologous stem cell transplantation as part of their treatment. Two years following treatment, the overall survival rate for patients in this study was 35%. There was a subgroup of these patients who had a survival rate of 55% after two years. These women were younger and in otherwise good health, possessed a certain microscopic type of cancer cell (non-clear cell) and were treated with HDC and stem cell transplantation during their first remission. The results from this study indicate patients with advanced ovarian cancer who undergo HDC and autologous stem cell transplant may experience improved survival times, particularly when this treatment strategy is used early in a patient’s treatment course.
Combined Approaches: Combining one or more new strategies may offer the greatest hope for patients. For example, a patient could receive dose-dense induction chemotherapy, followed by interval debulking and high-dose chemotherapy and autologous stem cell transplant, which together should produce the highest chance of achieving a complete remission. Patients in remission could then receive additional treatment with anti-cancer agents, such as maintenance chemotherapy or other biologic agents. Many combinations are being evaluated in clinical trials.
When Deciding on Treatment, Patients Should Ask the Following Questions:
Is there any evidence that the new treatment may be an improvement over conventional treatment? Since over 50% of patients with Stage IV disease may experience cancer recurrence, it may not be useful to compare the response rate to chemotherapy, the average duration of survival or time to relapse.
Instead, when evaluating treatment strategies, patients may want to compare the percentage of patients surviving with or without relapse 3-5 years from treatment to determine whether a treatment is truly more effective.
What is known about the risks or side effects of the new treatment? It is important to understand that patients experience more side effects with each treatment they receive. Since few patients with metastatic cancer are cured with standard initial treatment, prolonging the decision to receive a new treatment may result in greater side effects and a lesser chance of benefit.
1 Coleman, RL, Gershenson DM. Neoplastic diseases of the ovary: Screening, benign and malignant epithelial and germ cell neoplasms, sex-cord stromal tumors. In: Katz VL, ed. Comprehensive Gynecology, 5th ed. St. Louis: Mosby; 2007: 839-77.
2 Bristow RE, Eisenhauer EL, Santillan A, Chi DS. Delaying the primary surgical effort for advanced ovarian cancer: a systemic review of neoadjuvant chemotherapy and interval cytoreduction. Gynecologic Oncology. 2007;104:480-490.
3 Spannuth WA, Sood AK, Coleman RL. Angiogenesis as a strategic target for ovarian cancer therapy. Nature Clinical Practice Oncology. 2008;5:194-204.
4 Markman M, Liu PY, Wilczynski S et al. Phase III randomized trial of 12 versus 3 months of maintenance paclitaxel in patients with advanced ovarian cancer after complete response to platinum and paclitaxel-based chemotherapy: A Southwest Oncology Group and Gynecologic Oncology Group trial. Journal of Clinical Oncology. 2003; 21:2460-65
5 Armstrong DK, Bundy B, Lenzel L et al. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. New England Journal of Medicine. 2006;354:34-43.
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