Strategies to Improve Treatment - Stage II Ovarian Cancer
The following are all novel treatment strategies for treatment of ovarian cancer. They are currently being evaluated alone or in combination in clinical studies. Given the poor outcomes of treatment for ovarian cancer, the greatest benefit to patients wishing to pursue aggressive or potentially curative treatments may be participation in clinical studies that combine more than one of the following treatment strategies.
New chemotherapy regimens - Adjuvant chemotherapy with a platinum and taxane is currently the standard treatment for stage II ovarian cancer. Several new chemotherapy drugs including Doxil® (doxorubicin HCl) and Hycamtin® (topotecan) show promising anti-cancer activity when used for the treatment of more advanced ovarian cancer. Development of new multidrug chemotherapy treatment regimens that incorporate these or other additional anticancer therapies for use as adjuvant treatment is an active area of clinical research.
Higher-dose chemotherapy - Since conventional-dose chemotherapy appears to cure some women with ovarian cancer and since more chemotherapy kills more cancer cells, the delivery of very high doses of chemotherapy may be able to destroy enough cancer to improve a patient's chance of cure.
Several clinical trials have been performed that evaluate modest increases in the chemotherapy dose of Platinol® (cisplatin) and/or Cytoxan® (cyclophosphamide). Results of these trials have been inconsistent with only three of nine trials demonstrating improved patient outcomes with higher dose therapy.
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 severe 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.
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.
Neoadjuvant chemotherapy (before surgery) - Neoadjuvant refers to the administration of anticancer chemotherapy before surgery. When surgery is performed after chemotherapy treatment, it is referred to as interval debulking. 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.
Intraperitoneal therapy - Another treatment approach currently under evaluation is the use of intraperitoneal therapy for patients with advanced ovarian cancer. This treatment approach delivers the therapy directly into the abdominal cavity, where there is the greatest number of cancer cells.
Intraperitoneal therapy involves the delivery of therapy 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. In an attempt to improve survival rates, chemotherapy, biological response modifiers, and other agents are being tested in clinical trials evaluating intraperitoneal therapy.
Biological response modifiers - Biological response modifiers are naturally occurring or synthesized substances that direct, facilitate or enhance the body's normal immune defenses and are being evaluated as intraperitoneal therapy. Biologic response modifiers include interferons, interleukins, vaccines, and monoclonal antibodies.
Interferon gamma - In 1996, doctors in France observed that patients with ovarian cancer whose cancer had progressed following chemotherapy responded to intraperitoneal interferon gamma.
Proleukin® (aldesleukin) therapy - Aldesleukin is a biological modifier that has been used extensively to treat others cancers. Recently, phase I studies in women with ovarian cancer whose disease progressed following cisplatin-based chemotherapy have established a dose and schedule of aldesleukin that can be administered intraperitoneally.
Ethyol® (amifostine) - Because chemotherapy produces significant side effects, there is great interest in developing compounds that protect normal cells from chemotherapy damage. An additional advantage of reducing chemotherapy side effects is that the maximum amount of chemotherapy can be utilized to treat the cancer, as side effects often necessitate a dose reduction.
Ethyol is a compound that protects some organs from side effects of chemotherapy drugs and has been approved by the Food and Drug Administration for use with cisplatin (Platinol). Clinical trials are evaluating the use of Ethyol in combination with other chemotherapy agents in patients with advanced ovarian cancer.
Consolidative radiation therapy - Common treatments used after successful surgical debulking include radiation therapy that is delivered to the entire abdomen from an external machine or the administration of a radioactive suspension directly into the abdomen.
For a variety of reasons, primary chemotherapy drugs after surgical debulking have replaced radiation therapy since chemotherapy appears to be more effective for treating larger deposits of cancer with less severe side effects. Some centers are investigating whether the addition of radiation therapy after chemotherapy can improve cure rates in comparison to chemotherapy alone. The use of radiation therapy for patients who appear to have responded completely to surgical debulking and chemotherapy is an area of active investigation.
Gene therapy - Gene therapy involves the manipulation of genes in order to correct or override the abnormal alterations that cause cancer. This can be accomplished by replacing or inactivating a dysfunctional gene or replacing or inserting a functional gene.
Epidermal growth factor receptor (EGFR) inhibitors - Epidermal growth factor receptors (EGFR) are small proteins that are found on the surface of all cells. EGFR binds exclusively to small proteins circulating in the blood called growth factors.
The binding action between EGFR and growth factors stimulates biological processes within the cell to promote growth of a cell in a strictly controlled manner. However, in many cancer cells, EGFR is either abundantly overexpressed or the EGFR biological processes that normally stimulate cell growth are constantly active, leading to the uncontrolled and excessive growth of the cancer cell.
EGFR inhibitors block the EGFR pathway, thereby halting excessive cellular growth by inhibiting the EGFR process within a cell. Several EGFR inhibitors have been developed and are currently being evaluated in clinical trials.
Combined approaches - Combining one or more new strategies may offer the greatest hope. 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 anticancer agents, such as maintenance chemotherapy or other biologic agents. Many combinations are being evaluated in clinical trials.
This content was last modified on
July 23, 2007
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