A randomized phase III trial of cisplatin and tumor volume directed irradiation followed by carboplatin and paclitaxel vs. carboplatin and paclitaxel for optimally debulked, advanced endometrial carcinoma.

5505 Background: Patients with stage III/IVA uterine cancer (UC) carry high risk of systemic and local recurrence. Chemotherapy was shown to reduce systemic recurrence, however the risk of local failure remains high. Methods: The primary endpoint of this open label, randomized phase III trial was to determine if treatment with cisplatin and volume-directed radiation followed by carboplatin and paclitaxel for 4 cycles (C-RT, experimental arm) reduces the rate of recurrence or death (i.e., increases recurrence-free survival, RFS) when compared to carboplatin and paclitaxel for 6 cycles (CT, control arm) in patients with stages III-IVA ( grd 3 toxicity events in the C-RT arm and 227 (63%) in the CT arm. The most common > grd 3 events were myelosupression (40% vs. 52%), gastrointestinal (13% vs. 4%), metabolic (15% vs. 19%), neurological (7% vs. 6%), infectious (4% vs. 5%). Treatment hazard ratio for RFS was 0.9 (C-RT vs. CT; CI 0.74 to 1.10). C-RT reduced the incidence of vaginal (3% vs. 7%, HR = 0.36, CI 0.16 to 0.82), pelvic and paraaortic recurrences (10% vs. 21%, HR=0.43, CI 02.8 to 0.66) compared to CT, but distant recurrences were more common with C-RT vs. CT (28% vs. 21%, HR 1.36, CI 1 to 1.86). The analysis is premature for OS comparison. Conclusions: Although C-RT reduced the rate of local recurrence compared to CT; the combined modality regimen did not increase RFS in optimally debulked, stage III/IVA UC. Clinical trial information: NCT00942357.