Chemotherapy Superior to Whole-Abdominal Radiation Therapy for Uterine SarcomaKey Words
Uterine sarcoma, whole-abdominal radiation therapy, cisplatin; ifosfamide. (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary.)
Summary
Chemotherapy with cisplatin and ifosfamide was more effective than whole-abdominal radiation therapy at extending survival in patients with uterine sarcoma. However, better therapies are still needed for patients with this rare form of uterine cancer.
Source
American Society of Clinical Oncology (ASCO) annual meeting, Atlanta, June 3, 2006 (see the meeting abstract).
Background
Surgery is the most common treatment for uterine sarcoma, a rare cancer of the muscles or tissues that support the uterus. The disease accounts for just 3 to 5 percent of uterine cancers. No large-scale randomized clinical trial had explored what might be the best treatment to do after surgery (called adjuvant therapy) – chemotherapy or radiation.
The Study
This international phase III randomized clinical trial compared whole-abdominal radiation therapy (WAI) versus chemotherapy as adjuvant treatment for uterine carcinosarcoma. Women with any stage of cancer who had no more than 1 centimeter of tumor tissue left after surgery, and whose cancer had not spread outside the abdomen, were eligible to enroll in the trial.
Between 1993 and 2005, investigators enrolled 206 eligible women. No more than eight weeks after surgery, patients were randomly assigned to receive either WAI (105 women) or chemotherapy with cisplatin and ifosfamide plus the supportive drug mesna (102 women). Mesna protects the kidneys and bladder from chemotherapy drugs that could harm these organs. The investigators compared survival, location of first cancer recurrence, and treatment-related side effects between the WAI and chemotherapy groups. Patients were followed for an average of five years after treatment.
The trial was conducted by the Gynecologic Oncology Group, an NCI-funded cooperative cancer research group. The lead author of the study is Aaron H. Wolfson, M.D., of the University of Miami Miller School of Medicine.
Results
Without accounting for factors such as age and cancer stage, the death rate was 31 percent lower in the chemotherapy group - a statistically significant difference.
After adjusting for cancer stage, type of cells found in the tumors, and patients’ age, there was no statistically significant difference in the risk of cancer recurrence between the two groups, though there was a trend in favor of chemotherapy.
Patients older than 65 were more likely than younger patients to have their cancer recur after either treatment. Women receiving chemotherapy were more likely to have their cancer recur in the vagina than women receiving WAI, and women receiving WAI were more likely to have their cancer recur in the abdomen than women receiving chemotherapy.
More patients receiving chemotherapy experienced high-grade anemia (11 women versus 1 woman receiving WAI) and high-grade side effects in the nervous system (9 women versus none of the women receiving WAI). One patient in the chemotherapy group died during treatment; her death was attributed in part to chemotherapy-induced kidney failure. However, two patients in the WAI group died from radiation-therapy induced hepatitis (inflammation of the liver). In addition, more patients receiving WAI (six women versus none of the women receiving chemotherapy) had chronic gastrointestinal side effects after treatment.
Limitations
During the discussion after the ASCO presentation, Thomas Herzog, M.D., director of the Division of Gynecologic Oncology at Columbia University Medical Center in New York, pointed out that because the study enrolled patients over a 12-year period, the chemotherapy and radiation therapy techniques chosen at the beginning “may be challenged as somewhat obsolete.” In addition, the investigators were not able to enroll as many patients as planned into the trial due to the rarity of the cancer.
Comments
“We feel that adjuvant chemotherapy is certainly more effective…than radiotherapy” in reducing recurrence and prolonging survival for patients after surgery for uterine sarcoma, stated Wolfson, the study’s lead author. He suggested that future trials test vaginal brachytherapy (a form of local radiation therapy) in addition to chemotherapy, to reduce the risk of vaginal recurrence of the cancer.
Ted Trimble, M.D., M.P.H., a gynecologic cancer specialist with the National Cancer Institute’s Cancer Therapy Evaluation Program, agreed with Wolfson’s assessment, stating that “this trial does suggest that women with advanced carcinosarcoma of the uterus should be treated with primary surgery, vaginal brachytherapy, and systemic chemotherapy.”
New therapies are still urgently needed, said Herzog. “Overall poor survival calls for further innovation in treatment of carcinosarcoma, perhaps by adding brachytherapy to chemotherapy, or by adding additional chemotherapy cycles or changing the agents that are utilized to more contemporary chemotherapeutic agents.”
Back to Top |
