Eastern cooperative oncology group and american college of radiology imaging network randomized phase 2 trial of neoadjuvant preoperative paclitaxel/Cisplatin/Radiation Therapy (RT) or Irinotecan/Cisplatin/RT in Esophageal Adenocarcinoma: Long-Term Outcome and Implications for Trial Design

Purpose Toxicity, pathologic complete response, and long-term outcomes are reported for the neoadjuvant therapies assessed in a randomized phase 2 Eastern Cooperative Oncology Group and American College of Radiology Imaging Network trial for operable esophageal adenocarcinoma, staged as II-IVa by endoscopy/ultrasonography (EUS). Methods and Materials A total of 86 eligible patients began treatment. For arm A, preoperative chemotherapy was cisplatin, 30 mg/m², and irinotecan, 50 mg/m², on day 1, 8, 22, 29 during 45 Gy radiation therapy (RT), 1.8 Gy per day over 5 weeks. Adjuvant therapy was cisplatin, 30 mg/m², and irinotecan, 65 mg/m² day 1, 8 every 21 days for 3 cycles. Arm B therapy was cisplatin, 30 mg/m², and paclitaxel, 50 mg/m², day 1, 8, 15, 22, 29 with RT, followed by adjuvant cisplatin, 75 mg/m², and paclitaxel, 175 mg/m², day 1 every 21 days for 3 cycles. Stratification included EUS stage and performance status. Results In arm A, median overall survival was 35 months, and 5-, 6-, and 7-year survival rates were 46%, 39%, and 35%, respectively, whereas for arm B, they were 21 months and 27%, 27%, and 23%, respectively. Median progression- or recurrence-free survival (PFS) was 39.8 months with a 3-year PFS of 50% for arm A and 12.4 months (P=.046) with 3-year PFS of 28% for arm B. Eighty percent of the observed incidents of progression occurred within 19 months. Survival did not differ significantly by EUS and performance status strata. Conclusions Long-term survival was similar for both arms and did not appear superior to results achieved with other standard regimens.