Randomized Phase II Trial of Extended versus Standard Neoadjvant Therapy for Esophageal Cancer NCCTG (Alliance) Trial N0849
Randomized Phase II Trial of Extended versus Standard Neoadjvant Therapy for Esophageal Cancer
NCCTG (Alliance) Trial N0849
SR Alberts1, GS Soori2, Q Shi1,3, DA Wigle1, RP Sticca4, RC Miller1, JL Leenstra5, PJ Peller1, T-T Wu1, HH Yoon1, TF Drevyanko6, SJ Ko7, BI Mattar8, DA Nikcevich9, RJ Behrens10, MF Khalil11, GP Kim7
1Mayo Clinic, Rochester, MN; 2Missouri Valley Cancer Consortium, Omaha, NE; 3Alliance Statistics and Data Center, Rochester, MN; 4Meritcare Hospital CCOP, Fargo, ND; 5St. Vincent Regional Cancer Center CCOP, Green Bay, WI; 6Iowa Oncology Research Association CCOP, Des Moines, IA; 7Mayo Clinic, Jacksonville, FL; 8Wichita Community Clinical Oncology Program, Wichita, KS; 9Essentia Health Duluth Clinic CCOP, Duluth, MN; 10Iowa Oncology Research Association, Des Moines, IA; 11Geisinger Medical Center, Danville, PA
Patients (pts) with locally advanced esophageal or gastroesophageal junction (GEJ) adenocarcinoma commonly receive neoadjuvant chemoradiotherapy (chemo-RT). Despite this approach the rate of recurrence remains high. Given the difficulties of postoperative therapy, the efficacy of extended neoadjuvant therapy was assessed.
Eligibility criteria included T3-4,N0 – Tany,N(+) disease amenable to radiation and surgery. Pts were randomized to either arm A (docetaxel 60 mg/m2 day 1 , oxaliplatin [Oxal] 85 mg/m2 day 1, and capecitabine 1250 mg/m2/day days 1-14 x 2 cycles [DOC] followed by 5-FU 180 mg/m2/day continuous IV through radiation + Oxal 85 mg/m2 days 1,15,29 + 50.4 Gy radiation (chemo-RT)) orarm B (chemo-RT alone). Randomization was stratified by ECOG PS (0/1 vs 2) and stage (II vs III/IVA). Primary endpoint was pathologic complete response (PCR) rate, defined as no gross or microscopic tumor identified in the surgical specimen. Interim analysis assessed efficacy and futility of the experimental intervention. Wilcoxon rank sum and Fisher’s exact tests were used to compare clinical/pathologic factors between arms.
Baseline and stratification factors were well balanced between arms. Of 42 pts included in the interim analysis (86% male; age [median 63, range 38-88], 100% PS 0/1; 71% stage III; 55% esophagus, 40% GEJ; 36% measurable disease), 4 and 1 pts in arms A and B, respectively, did not have surgery due to death (A, 2), progressive disease (A, 1), alternative treatment (A, 1) or adverse event (B, 1). Among 21 arm A pts, 21, 20, and 19 pts started 1st cycle of DOC, 2nd cycle of DOC and chemo-RT, respectively. All arm B pts received chemo-RT. 33% (7/21) of arm A and 48% (10/21) of arm B pts achieved PCR (p=0.53). Among pts undergoing surgery, 94% (16/17) and 100% (20/20) of arm A and B pts had complete resection (p=0.46). 38% and 29% of arm A and B pts experienced at least one grade 4+ adverse event at least possibly related to treatment (p=0.74).
Extended neoadjuvant therapy in pts with locally advanced esophageal or GEJ adenocarcinoma failed to improve the PCR rate. Follow-up in regard to survival and rate of recurrence is ongoing.
Figure 1: CONSORT Diagram
Table 1: Patient Characteristics
Early toxicity assessment portion
Docetaxel 60 mg/m2 day 1, Oxaliplatin 85 mg/m2 day 1, and Capecitabine 1250 mg/m2/day days 1-14 x 2 cycles [DOC]; 5-FU 180 mg/m2/day continuous IV through radiation + Oxal 85 mg/m2 days 1,15,29 + 50.4 Gy radiation (chemo-RT)
Patient Eligibility Criteria
Statistical Design and Analysis
Table 2: Pathologic Complete Responses
Table 3: Adverse Events
Combined modality therapy with chemotherapy and radiation, prior to surgery, remains the standard of therapy for patients with adenocarcinoma of the esophagus and GEJ
This study was conducted as a collaborative trial of the North Central Cancer Treatment Group, Mayo Clinic and the Alliance and was supported in part by Public Health Service grants CA-25224, CA-37404, CA-35431, CA-35269, CA-35101, CA-35448, CA-60276, CA-35113, CA-35267, CA-35090, CA-35415, CA-35119, and CA-63848 from the National Cancer Institute, Department of Health and Human Services. The content is solely the responsibility of the authors and does not necessarily represent the views of the National Cancer Institute or the National Institute of Health.