Induction Chemoradiotherapy for Esophageal Cancer: Comparing Carboplatin/Paclitaxel with Cisplatin/5-FU

Abstract

Purpose: Since publication of the CROSS trial in 2012, trimodality therapy using carboplatin/paclitaxel (“CP”) has become the standard of care in the treatment of locally advanced esophageal cancer. Yet few studies have directly compared CP to its predecessor, cisplatin/5-fluorouracil (“CF”), and little is known about the comparative efficacy of these two regimens. The purpose of this study is to directly compare the antineoplastic potency of these two regimens as components of trimodal therapy in the treatment of locally advanced esophageal cancer. Patients and Methods: Patients completing trimodal therapy with CP or CF for locally advanced esophageal cancer at a single institution from 2002 to 2017 were included in this retrospective study. Clinical and treatment details were obtained from medical records. The primary outcome was pathologic complete response (pCR). Secondary outcomes were overall (OS) and disease-free survival (DFS). Primary outcomes were measured with logistic regression; survival was estimated with Kaplan-Meier and Cox proportional hazards models. Results: 325 patients were included. 186 patients (57%) received CP; 139 (43%) received CF. Median follow-up was 23.1 months. Tumor stages were similar between groups (P=.89). CF was associated with improved pCR compared to CP in both univariate (33% vs. 21% respectively, P=.02) and multivariate (OR 2.2, P=.01) analyses. pCR was associated with significantly improved 5-year OS (60% vs. 31%, P<.001). CF showed improved median OS compared to CP (42 vs. 29 months, P=.04). In multivariate analysis, CF was associated with improved OS (HR .668, P=.02) and DFS (HR .708, P=.04) compared to CP. Conclusions: Trimodal therapy with CP has become the standard of care for curative treatment of LAEC, yet most studies compare it against surgery alone. Here we directly compare CP to the historical standard regimen (CF), finding that, amongst patients who complete trimodal therapy, CP is associated with worse tumor response and survival. These observations invoke caution that the anti-tumor efficacy of the CROSS regimen is reduced compared to CF and is more dependent on tumor histology. Alternative induction chemotherapy strategies should be evaluated in esophageal carcinoma.