Women with Stage III ovarian cancer given a combination of intravenous and intraperitoneal chemotherapy following surgical debulking of tumor had a median survival nearly 16 months longer than women who received IV chemotherapy alone, according to a study published conducted by the Gynecologic Oncology Group (GOG), a National Cancer Institute-supported research network, in the New England Journal of Medicine.
The study, led by Deborah Armstrong at the Johns Hopkins Kimmel Cancer Center in Baltimore, Maryland, builds upon evidence from eight other clinical trials showing an overall survival benefit of approximately one year for women treated with IP chemotherapy after "optimal debulking"--surgery to remove most, if not all, of the cancer in the abdomen.
Based on this overwhelming evidence, the NCI issued a clinical announcement encouraging the administration of a combination of intravenous (IV, into a vein) and intraperitoneal (IP, delivered directly into the abdomen or peritoneal cavity) chemotherapy to women with advanced ovarian cancer, who have undergone optimal surgical debulking.
The University of Chicago Hospitals participated in the NCI-supported clinical trials which led to this clinical announcement.
"We are making incremental improvements in the survival of women with ovarian cancer," said Diane Yamada, MD, principal investigator for the GOG at the University of Chicago and section chief for gynecologic oncology.
"The results of this GOG trial highlight two important points," she added. "First is the importance of clinical trial participation for patients diagnosed with gynecologic malignancies, and second is the importance of being adequately educated about who is performing your surgery and what their qualifications are when you, as a patient, potentially have an ovarian cancer."
The trial involved 429 women with stage III ovarian cancer who were given chemotherapy following the surgical removal of tumors. Investigators randomly grouped women into two categories: those who would get all chemotherapy intravenously or those who would get chemotherapy both intravenously and IP, through a spaghetti-like tube called a catheter that was inserted directly into the peritoneal cavity.
"The catheter allows us to bathe the entire abdominal area with a high concentration of chemotherapy for a long period of time, which appears to be better at destroying lingering cancer cells," said Hopkins' Armstrong.
While the abdominal area is the main site for ovarian cancer spread, the intravenous route of chemotherapy is needed to catch cancer cells that may have spread outside the abdomen.
Overall survival for 205 patients receiving IP chemotherapy in the study was an average of 65.6 months, a 25 percent improvement over the intravenous-only group (49.7 months) of 210 patients.
Similarly, relapse-free survival for those receiving intraperitoneal chemo was 23.8 months compared with 18.3 months for the intravenous-alone group, a 20 percent improvement.
Side effects, however, such as suppressed blood counts and neurological problems, were significantly worse for the group receiving IP chemotherapy. They reported poorer quality of life during their treatment.
Complications associated with the abdominal catheter used to deliver the IP chemotherapy were the main reason only 86 of the women completed all six IP treatments. Women who received IP chemotherapy had more side effects than those treated with IV chemotherapy alone, but most side effects were temporary and easily managed. One year after treatment, women in both study groups had the same reported quality of life.
"Although this advantage comes at the expense of increased toxicity and reduced quality of life during treatment," note the authors, "these results should encourage the use of intraperitoneal chemotherapy in patients with advanced ovarian cancer."
IP therapy is not a new treatment approach. It was first studied half a century ago for colon cancer but never gained popularity for ovarian cancer, despite several studies that hinted at survival benefits.
Standard treatment for women with stage III ovarian cancer has been surgical removal of the tumor (debulking), followed by six to eight courses of IV chemotherapy given every three weeks with a platinum drug, such as cisplatin or carboplatin, and a taxane drug, such as paclitaxel.
The NCI now recommends that women with advanced ovarian cancer who undergo effective surgical debulking receive a combination of IV and IP chemotherapy.
"Randomized, multicenter clinical trials, including this most recent study, clearly show the value of IP chemotherapy--an extended life for women with advanced ovarian cancer," said Philip DiSaia, MD, chairman of the GOG.
More studies are needed to determine the best IP drug regimen and the optimal number of IP treatments. Some of those studies are currently ongoing at the University of Chicago said Yamada. Future trials also will address how to reduce toxicity associated with IP administration.
The University of Chicago's multidisciplinary team of gynecologic oncologists, medical oncologists, radiation oncologists, and pathologists "will continue to be committed to providing patients with as many pre- and post-surgical treatment options as possible," Yamada said. "We encourage clinical trial participation in the hopes that we will improve the outcome for our patients with gynecologic malignancies."
An estimated 22,220 women in the United States were diagnosed with ovarian cancer in 2005. It causes more deaths in the United States than any other cancer of the female reproductive system, with an estimated 16,210 women dying from the disease in 2005.
The most recent statistics show that only 45 percent of women survive five years after being diagnosed with ovarian cancer; the rate increases to 94 percent when the disease is diagnosed before it has spread. However, women with ovarian cancer frequently have no symptoms or only mild symptoms until the disease is advanced. As a result, only 19 percent of all cases are detected at that early, localized stage.