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Key Words

Endometrial cancer, whole-abdominal radiotherapy, doxorubicin, cisplatin. (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary.)

Summary

After surgery for advanced endometrial cancer, the chemotherapy combination of doxorubicin (Adriamycin®) and cisplatin (Platinol®) was more effective than radiation to the whole abdomen in terms of both overall and progression-free survival. However, results from other more recent trials may yet show a survival benefit from radiotherapy for this group of cancer patients.

Source

The Journal of Clinical Oncology, Jan. 1, 2006; published online December 5, 2005 (see the journal abstract).
(J Clin Oncol. 2005 Dec 5; Epub ahead of print)

Background

Cancer of the uterus is known as endometrial cancer and is the most common gynecological cancer in the United States. Some 40,880 new cases were expected to develop in 2005, nearly three in four among women between the ages of 45 and 74. If detected at an early stage, it can often be cured by surgery to remove the uterus and ovaries.

Endometrial cancer is classified as advanced if it has spread beyond the cervix (the neck or lower part of the womb). The disease traditionally has been treated with surgery followed by radiation directed to the entire stomach region (called whole-abdominal radiation), an approach that risks damage to the nearby kidneys and liver, which are particularly sensitive to radiation. However, there is no evidence that radiotherapy extends the lives of such patients and adjuvant (additional) chemotherapy is also sometimes given to reduce the symptoms of the disease and the side effects of treatment.

The Study

The Gynecologic Oncology Group (GOG) 122 trial was the first major phase III clinical trial to compare chemotherapy to whole-abdominal radiation as first-line, post-surgery therapy for advanced endometrial cancer. Early results were first presented at the annual meeting of the American Society for Clinical Oncology in Chicago in June 2003.

Between May 1992 and February 2000 researchers enrolled 396 patients with stage III or IV endometrial cancer at sites around the country. All patients had hysterectomies and surgery to remove their uterus and were left with no tumors larger than an inch. Within eight weeks, 198 randomly assigned patients received whole-abdominal radiation, while the other 190 received combination chemotherapy with doxorubicin and cisplatin.

Patients receiving radiation got 1.5 Gy to their whole abdomen each weekday for four weeks, and then a cumulative boost dose of 15 Gy specifically to their pelvic region, for a total of 45 Gy. About 84 percent of patients finished the full course of radiation.

Patients receiving chemotherapy got a combination of doxorubicin and cisplatin in seven three-week cycles, followed by one cycle of cisplatin alone. Only 63 percent of patients finished the full course of combined chemotherapy.

Patients were monitored for side effects each week during treatment. After treatment, they were seen every three months for two years, twice each year thereafter.

Marcus E. Randall, M.D., from the Brody School of Medicine at East Carolina University, Greenville, N.C., is the lead author of the report. The trial was supported by the National Cancer Institute.

Results

After a median follow-up of about six years (74 months), patients who received chemotherapy were 29 percent less likely to have their cancer recur or progress and 32 percent less likely to die than those receiving whole-abdominal radiation. (These statistically significant figures were reached after taking into account – adjusting for – the patients’ different cancer stages.)

As expected, adverse effects of treatment were more severe in the chemotherapy group, though researchers deemed them to be generally manageable. The primary adverse effect of chemotherapy was blood toxicity, affecting 88 percent of this group compared to 14 percent for those receiving radiation. Less frequent but still significant problems with the heart and nervous system were also more common among the chemotherapy patients. Eight deaths were attributed to the chemotherapy treatment, and five to radiation treatment.

Limitations

Neither whole-abdominal radiation or the particular doxorubicin-cisplatin combination used in this trial are still commonly used. Doctors now generally supplement doxorubicin-cisplatin with paclitaxel (Taxol®), a drug that is also sometimes given in an alternate combination with carboplatin (Paraplat®). Radiotherapy is now more commonly confined to the pelvis and more precisely targeted, allowing for higher doses.

In addition, the study’s authors acknowledged that radiation to the whole stomach “may not be the most effective radiotherapy approach,” especially in patients with more advanced cancers, and that chemotherapy approaches with greater efficacy and less toxicity are needed.

Comments

Nonetheless, in an accompanying editorial, Gini F. Fleming, M.D., of the University of Chicago, called these results “a milestone in the treatment of endometrial cancer.” She noted that advanced stage endometrial tumors with certain unfavorable characteristics are not very common. Thus, it is hard to find enough patients for meaningful clinical trials and no clear treatment choice had been established. After this trial, combination chemotherapy of some kind should now be the standard first-line, post-surgery treatment for this group of patients, she wrote.

“Radiation can still be effective at local control, however,” said Ted Trimble, M.D., Ph.D., of NCI’s Cancer Therapy Evaluation Program, “and can even cure some cancers that recur in the pelvic area. But,” he added, “radiotherapy does not increase overall survival, as even this earlier combination of chemotherapy clearly did.”

Current approaches to treatment, he said, are heading toward surgery followed by some combination of chemotherapy and radiotherapy, “but it is clear we need to learn how to reduce the toxic effects of chemotherapy in this setting.”

At least two ongoing clinical trials concerned with endometrial cancer (GOG 184 and GOG 209) are testing newer drug combinations and using more precise radiotherapy techniques. The results should clarify some of these issues.

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