High-Risk Endometrial Cancer Patients Helped with Radiotherapy and Concurrent Chemotherapy After Surgery

Endometrial cancer is the most typical gynecologic malignancy. Patients with early-stage disease are typically treated with surgery alone; however, patients with advanced endometrial cancer have higher instances of local or distant recurrence. Concurrent radiation therapy and chemotherapy after surgery is used to reduce the rate of recurrence in patients with advanced disease. This study assessed the effectiveness and toxicity of concurrent chemoradiation with weekly paclitaxel in patients with stage III and IV endometrial cancer.

From January 2006 to March 2008, 57 patients from 20 institutions in Korea were included in the study. Patients eligible to participate in the study were between 20 and 80 years old, with a histologic diagnosis of International Federation of Gynecology and Obstetrics (FIGO) stage III or IV endometrioid adenocarcinoma with no history of prior surgery, radiation therapy, or hemotherapy for the treatment of other cancers.

Patients with diagnoses of other cancers or severe infection requiring parenteral antibiotics, with a history of cardiac arrhythmia, congestive heart failure or myocardial infarction within the previous six months, or with uncontrolled diabetes, infection, hypertension or compromised cardiac, renal, liver or bone marrow functions were not included in the study. Of the 57 patients in this study, 12 patients (21.1%) had FIGO stage IIIA disease, 40 (70.1%) had FIGO stage IIIC disease and five (8.8%) had FIGO stage IV disease. Fourteen patients (24.6%) had grade 1 tumors, 27 (47.3%) had grade 2 tumors, and 16 (28.1%) had grade 3 tumors. The average age of the study patients was 52.2 years old.

All eligible patients had a staging laparotomy, including total abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic and para-aortic lymphadenectomy and peritoneal washing cytology. Patients in the study received a total dose of 45.0–50.4 Gy of external pelvic radiation therapy (1.8–2.0 Gy daily, five times a week), and 60 mg/m2 of paclitaxel diluted in 500 m of 5% dextrose in water administered intravenously for three hours, once a week, for six weeks. Radiotherapy and chemotherapy were initiated within six weeks of surgery, and radiation therapy began either two days before or two days after the first chemotherapy treatment.

Chemotherapy was deferred due to adverse toxic effects in two patients. Of those two patients, one experienced septic shock, and one had persistent grade 4 neutropenia for more than two weeks. One patient refused treatment after enrollment, and two patients withdrew from treatment prior to completing all six cycles of chemotherapy. Fifty-two patients were included in the study’s final analysis.

Patients received follow-up for five years after surgery. Chest X-ray and abdominal-pelvic computed tomography (CT) or magnetic resonance imaging (MRI) scanning were done every six months for the first two years post-surgery and then yearly for the next three years. Patients were also assessed by pelvic examinations, monitoring CA125 blood serum levels and Papanicolaou tests every three months for the first two years post-surgery and then every six months for the next three years.

Severe toxicities observed during treatment were primarily hematologic toxicities. Of the 312 treatment cycles (52 patients each received six cycles), 52 episodes (16.7%) of grade 3 or 4 leukopenia (decrease in number of white blood cells) were observed, and 35 episodes (11.2 percent) of grade 3 or 4 neutropenia were observed. Hematologic toxicity caused 98 cycles to be delayed one week, and a paclitaxel dose reduction was required for eight patients (15.3%) who experienced persistent neutropenia for more than one week.

Disease recurrence occurred in 19 (36.5%) of the 52 patients in the final analysis. Eighteen patients (34.6%) experienced extrapelvic recurrence (lung, liver, bone, para-aortic, lymph node, or other sites). One patient (1.9%) had intrapelvic recurrence in the vaginal vault. The median time to the detection of recurrence was 12 months (range 3 to 24 months).

Survival data were available for all 52 patients included in the study. By the end of the five-year follow-up period, nine patients (17.3%) had died of endometrial cancer. For all patients included in the study, the five-year disease-free survival rate was 63.5 % (95% confidence interval [CI]), and the overall survival rate was 82.7% (95% CI).

“There is a lack of clear evidence on the best adjuvant treatment plan for patients with advanced endometrial cancer. There is growing evidence that chemotherapy should be administered to patients with advanced disease in addition to radiation therapy,” said Jae-Hoon Kim, MD, PhD, a coauthor of the study, head of the department of obstetrics and gynecology at Gangnam Severance Hospital (Seoul, South Korea), and a professor in the department of obstetrics and gynecology at Yonsei University College of Medicine (Seoul, South Korea). “This study shows that concomitant radiation therapy and weekly paclitaxel chemotherapy is a reasonable treatment option for patients with advanced endometrial cancer that can reduce toxicity and reduce pelvic recurrence. These favorable findings should be further evaluated in a larger, prospective, randomized, controlled study to validate this treatment approach.”

Related Links:
Gangnam Severance Hospital
Yonsei University College of Medicine