Overview

Patients diagnosed with stage II ovarian cancer have cancer that is limited to the ovaries and other pelvic organs, but has not spread to the upper abdomen, lymph nodes or sites outside the abdomen.

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 II 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 II ovarian cancer consists of both surgery and chemotherapy. Patients with stage II ovarian cancer may experience a range of outcomes following standard treatment. Patients with stage IIA disease experience cancer recurrence rates of 30-40%. However, 60-80% of patients with more advanced stage IIB disease may develop cancer recurrence. This is because patients with stage II ovarian cancer are often left with microscopic disease and currently available chemotherapy is unable to eradicate all of the remaining cancer.

Surgical Cytoreduction

Surgical cytoreduction (also called debulking) refers to surgical removal of as much of the cancer as possible. Cytoreduction 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 cytoreduction live longer and have a longer time to cancer recurrence than patients who have had suboptimal cytoreduction.

Following cytoreductive surgery, all patients with stage II ovarian cancer are offered additional treatment. This is because many patients with stage II disease have small amounts of cancer that have spread outside the ovary and were not removed by surgery. An effective treatment is needed to eliminate the remaining cancer in order to improve the cure rate achieved with surgical removal of the cancer. Currently, this treatment is chemotherapy.

The combination of cytoreductive surgery and chemotherapy treatment is the standard of care for treatment of stage II ovarian cancer. Researchers have also looked at initiating treatment with neoadjuvant chemotherapy, in order to decrease the tumor burden, then performing cytoreductive surgery, followed by several more cycles of adjuvant chemotherapy. This format has been compared with the more traditional sequence of surgery followed by adjuvant chemotherapy. Most research has not shown a benefit to the chemo-surgery-chemo format, although some work is looking at whether this format might be applicable to patients who are suspected of having potentially unresectable disease. In this case, current guidelines recommend chemotherapy for three cycles, followed by an interval cytoreductive surgery, and then the final three cycles of chemotherapy. Researchers are also continuing to evaluate the use of a second or interval cytoreductive surgery to be performed after the chemotherapy has had a chance to further decrease the amount of cancer.

Systemic Chemotherapy for Stage II Ovarian Cancer

It is important to understand that many patients with ovarian cancer already have small amounts of cancer that were not removed with surgery or have spread away from the ovaries. These cancer cells cannot be detected with any of the currently available tests and are referred to as micrometastases. The presence of micrometastases causes cancer recurrence following treatment with surgery alone. An effective treatment is needed to cleanse the body of micrometastases in order to improve a patient’s duration of survival and potential for cure. The delivery of cancer treatment following local treatment with surgery is referred to as “adjuvant” therapy.

A chemotherapy regimen that is commonly used in the treatment of ovarian cancer involves a combination of Paraplatin® (carboplatin) and Taxol® (paclitaxel). 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.

Before deciding to receive adjuvant chemotherapy treatment or to participate in a clinical trial, women should ensure they understand the answer to 3 questions:

  • What is my prognosis (risk of cancer recurrence) without adjuvant chemotherapy treatment?
  • How will my prognosis be improved with treatment?
  • What are the risks of treatment?

Strategies to Improve Treatment

The progress that has been made in the treatment of ovarian cancer has resulted from improved development of adjuvant 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 II ovarian cancer.

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 an 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.1

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. Avastin may also improve the delivery of chemotherapy to cancer cells by normalizing blood supply.

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.

Neoadjuvant Chemotherapy: Neoadjuvant chemotherapy refers to chemotherapy that is given prior to surgery. When surgery is performed after chemotherapy treatment, it is referred to as interval cytoreduction. Some doctors believe that neoadjuvant chemotherapy can reduce the size of the cancer, thereby allowing easier surgical removal and more effective results from the subsequent chemotherapy. Although ongoing work is being done to explore the neoadjuvant chemotherapy-surgery-adjuvant chemotherapy format, current results do not suggest that this format shows an advantage over the more conventional format of surgery followed by adjuvant chemotherapy. There are current clinical trials attempting to further define the answer to this question.5

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 may 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.

References:


1 Armstrong DK, Bundy B, Lenzel L et al. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. New England Journal of Medicine. 2006;354:34-43.

2 ACOG Committee on Gynecologic Practice. Intraperitoneal chemotherapy for ovarian cancer. Obstetrics and Gynecology. 2008;111:249-251.

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;

5 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.

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