Because endometrial carcinoma is a heterogeneous disease, it is often difficult to treat, and women diagnosed with advanced disease are at risk for local and systemic recurrence. When researchers tested platinum-based chemotherapy plus radiation therapy against chemotherapy alone in patients with stage III or IVA endometrial carcinoma to see which treatment improved outcomes the most, they discovered that chemoradiotherapy did not improve outcomes more so than chemotherapy alone.
This study, results of which were published in The New England Journal of Medicine, enrolled 813 patients with surgical stage III or IVA endometrial carcinoma according to FIGO 2009 staging criteria of any histologic subtype or with FIGO 2009 surgical stage I or II clear-cell or serous endometrial carcinoma and peritoneal washings positive for cancer cells. In order to be eligible, patients needed to have received a hysterectomy and bilateral salpingo-oophorectomy within eight weeks prior to trial entry.
Participants were randomly assigned in a 1:1 ratio to receive either chemoradiotherapy or chemotherapy alone. The chemoradiotherapy regimen consisted of 50 mg/m2 intravenous cisplatin on days 1 and 29 in conjunction with volume-directed external-beam radiation therapy (EBRT), followed by carboplatin at a dose that achieved an area under the concentration-time curve of 5 to 6 plus 175 mg/m2 paclitaxel every 21 days for four cycles, with granulocyte colony-stimulating factor support. The EBRT dose was delivered to the pelvis with or without paraaortic fields at a dose of 4500 cGy in 25 fractions at 180 cGy per fraction. The chemotherapy-only group received carboplatin at a dose to achieve an area under the concentration-time curve of 6 in combination with paclitaxel, 175 mg /m2, every 21 days for six cycles. The median follow-up was 47 months.
The percentage of patients alive and relapse-free at 60 months was 59% in the chemoradiotherapy group and 58% in the chemotherapy-only group. Chemoradiotherapy lowered the five-year incidence of vaginal recurrence and pelvic and paraaortic lymph-node recurrence compared with chemotherapy alone. However, distant recurrence was more common in association with chemoradiotherapy.
The most common adverse events of any grade reported in both groups included blood or bone marrow events, gastrointestinal events, and fatigue.
"In this randomized trial, the combined regimen of chemotherapy plus radiation did not provide a benefit over chemotherapy alone with respect to relapse-free survival in patients with stage III or IVA endometrial carcinoma," conclude the authors of the study. "Our data are compatible with the hypothesis from previous studies that completion of chemotherapy is important for the prevention of disease relapse."
For More Information
Matei D, Filiaci V, Randall ME, et al (2019). Adjuvant chemotherapy plus radiation for locally advanced endometrial cancer. N Engl J Med, 380:2317-2326. DOI:10.1056/NEJMoa1813181
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