(S034) Pilot Phase II Trial of “Sandwich” Radiation and Combination Carboplatin and Paclitaxel Chemotherapy in Patients With High-Risk Endometrial Cancer

Lori Spoozak, MD, MHS, Divya Gupta, MD, Laura Reimers, MPH, Jennifer Jorgensen, MD, Rafi Kabarriti, MD, Keyur Mehta, MD, Gary Goldberg, MD, Mark Einstein, MD, MS, Dennis Yi-Shin Kuo, MD; Albert Einstein College of Medicine; Weill Cornell Medical College

OBJECTIVES: We sought to determine the toxicity, tolerability, and outcome of radiation therapy (RT) sandwiched between combination chemotherapy in patients (pts) with high-risk endometrial cancer.

METHODS: High-risk endometrial cancer was defined as surgically staged endometrioid adenocarcinoma, IA with grade (G) 3 tumor and with lymphovascular space involvement, IB with G2 or 3 tumor, and stage II–IV disease, any grade. Treatment involved paclitaxel (T) (175 mg/m²) and carboplatin (C) (area under the concentration-time curve [AUC] = 6.0 or 6.5) every 21 days × 3 doses, followed by pelvic external beam radiation therapy (45 Gy) and brachytherapy (15 Gy). Per protocol, brachytherapy only (25 Gy) was administered to pts with stage IA G3 and IB G2 disease. Three additional cycles of T/C (AUC = 5) were administered after RT. Toxicity was graded by Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0). Analysis of toxicities was performed on all evaluable pts.

RESULTS: A total of 21 pts were enrolled between 2008–2014. The median age was 62 years (range: 48–74 yr): 66.7% (14/21) pts had stage I/II disease, while the remaining 33.3% (7/21) had stage IIIC disease; 42.9% (9/21) had International Federation of Gynecology and Obstetrics (FIGO) G1 disease, and 23.8% (5/21) and 33.3% (7/21) had G2 and 3 disease, respectively; 66.7% (14/21) pts completed the treatment per protocol; and 76.2% (16/21) pts completed six cycles of chemotherapy. One pt refused chemotherapy after enrollment, and four pts could not complete chemotherapy due to hematologic toxicities. Of 115 evaluable chemotherapy cycles, the G3 or 4 combined hematologic toxicity events were as follows: 33/115 cycles (28.7%) neutropenia, 9/115 cycles (7.8%) thrombocytopenia, and 10/115 cycles (8.7%) anemia. Of 105 evaluable chemotherapy cycles, the G3 or 4 combined nonhematologic events were as follows: 2/105 cycles (1.9%) infection, 1/105 cycles (0.95%) neuropathy, 4/105 (3.8%) metabolic, and 1/105 (0.95%) venous thromboembolism. Dose reduction occurred in 6/115 cycles (5.2%), and dose delay occurred in 12/115 cycles (10.4%). Since the study onset, 1 of 21 pts had a recurrence (lung) and died of disease.

CONCLUSIONS: Sandwich chemotherapy and radiation therapy is a tolerable treatment modality for patients with high-risk endometrial cancer. Rates of hematologic toxicities are acceptable, and nonhematologic toxicities are uncommon. Further enrollment of patients is underway to determine efficacy.

Proceedings of the 97th Annual Meeting of the American Radium Society- americanradiumsociety.org