Results from a phase III clinical trial initially presented more than 2 years ago have been published and, according to several experts, represent a new standard of care for treating women with advanced endometrial cancer. In the trial, adjuvant chemotherapy improved overall and disease-free survival compared with whole abdominal irradiation (WAI) in women with advanced disease. The results were released early online by the Journal of Clinical Oncology (JCO) on December 5.

Led by the Gynecologic Oncology Group (GOG), the NCI-funded trial, GOG 122, is the first to show a survival benefit for adjuvant chemotherapy in this patient group. In a commentary in JCO, Dr. Gini F. Fleming of the University of Chicago called the results "a milestone in the treatment of endometrial cancer."

According to the trial's lead investigator, Dr. Marcus Randall of the Brody School of Medicine at East Carolina University, the results should make WAI a relic of the past for most women with advanced disease. "Based on the results of this study, WAI should have no role or close to no role in managing these patients," he said.

The 422 women in the trial had stage III or IV endometrial carcinoma with a maximum of 2 cm of postoperative residual disease: 202 received WAI after surgery and 194 received 7 cycles of doxorubicin and cisplatin, plus a single cisplatin cycle. At 60 months, 55 percent of patients in the chemotherapy arm were alive, compared with 42 percent of patients in the WAI arm; disease-free survival was 50 percent vs. 38 percent, respectively.

The chemotherapy regimen in GOG 122, which began accruing patients in 1992, has fallen out of favor for treating many solid tumors because of toxicity. Not surprisingly, patients in the chemotherapy arm were far more likely to have high-grade hematologic toxicities such as low white blood cell levels and gastrointestinal effects. Only 63 percent of patients completed the full chemotherapy regimen, compared with 84 percent of those treated with WAI.

Surgery is the first-line treatment for endometrial cancer. Because most patients present with stage I disease, hysterectomy can often be curative, according to Dr. Edward Trimble of NCI's Division of Cancer Treatment and Diagnosis (DCTD).

Surgery also helps clinicians stage the disease and make more informed decisions about next treatment steps. Stage I disease, for example, means the tumor is confined to the uterus. Stage III disease indicates the disease has spread, often to the lymph nodes.

According to Dr. Randall, community oncologists are already using adjuvant chemotherapy to treat advanced disease, a trend that began after the initial release of the trial's results at the American Society of Clinical Oncology annual meeting in 2003.

Clearly, though, the toxicity seen with the doxorubicin/cisplatin regimen has affected how adjuvant chemotherapy is being employed.

While there are no data from randomized trials in endometrial cancer to necessarily support it, Dr. Trimble said, "A lot of oncologists are using carboplatin and paclitaxel, which is better tolerated."

GOG is conducting a phase III trial comparing carboplatin and paclitaxel with doxorubicin, cisplatin, and paclitaxel for advanced disease.

The GOG 122 trial is by no means the death knell for radiation, Dr. Trimble continued, particlarly radiation therapy that is more focused on known tumors. "There is room to study radiation because we know it helps with local control," he said. "We think the new paradigm may be a tri-modality therapy, with surgery plus chemotherapy and radiation."

By Carmen Phillips